L-methylfolate is an active form of folic acid which enters the brain. Folic acid supplementation has been considered for decades in treating depression, with varying results (generally mildly positive). The mechanism in the brain is generally as an indirect enhancer of the production of neurotransmitters, through its involvement in the metabolic pathway.
Here are some recent studies looking at l-methylfolate as an augmentation:
http://www.ncbi.nlm.nih.gov/pubmed/21311704
Here, a dose of 15 mg/day of l-methylfolate (but not 7.5 mg) added to an SSRI led to a doubling of the response rate for depressed patients, after 30 days (about 30% vs. 15%). These patients had previously been on the same SSRI alone without response. There were no side effect problems.
http://www.ncbi.nlm.nih.gov/pubmed/23212058
Another positive study from 2011. Again showing a significant improvement in response rate with l-methylfolate augmentation, with no side effect problems (probably fewer side effects in the folate group). But this is a much weaker study due to it being retrospective.
As I look further at this I see some controversy about whether there may be bias here, as the methylfolate is quite an expensive product. I would want to see a comparison study between methylfolate and the much more inexpensive ordinary folic acid. In discussions I've looked at pertaining to this issue, the argument is made that the dose of ordinary folic acid would be very high to match 15 mg of l-methylfolate. Maybe so--but it would be very simple to do a comparison study, since if there is no clinical superiority of one over the other, then the more affordable product should be recommended.
Showing posts with label Depression. Show all posts
Showing posts with label Depression. Show all posts
Wednesday, January 9, 2013
Tuesday, January 8, 2013
Interesting Augmentations 1: creatine + SSRI
From my annual review of articles from psychiatry journals, here is the first of a few which caught my eye: they're very simple studies looking at medication augmentations.
An augmentation refers to adding some type of therapeutic agent (usually a medication) to help make another therapeutic modality work better. Usually an augmentation would not be expected to help much on its own--the term implies that it must be used with something else. Typical augmentations in common use are triiodothyronine (a form of thyroid hormone) or lithium added to antidepressants to treat depression.
It's always nice to see an article which has an extremely simple premise (e.g. to try some new therapy or other), which could be readily applied in an attempt to help someone immediately.
The first article is from a Korean group (Lyoo et al.) published in the American Journal of Psychiatry in September 2012. ( http://www.ncbi.nlm.nih.gov/pubmed/22864465 ) They looked at treating 52 women having a major depressive episode, with either escitalopram 10-20 mg/day plus placebo, or escitalopram 10-20 mg plus 5 grams of creatine monohydrate daily.
From the second week of treatment onwards, the creatine group had better symptom improvement. After 8 weeks, over 50% of the creatine group met criteria for remission, compared to only about 25% of the placebo group.
Creatine has been used for years as a type of muscle-building supplement. It may have some benefits for various neuromuscular and other neurological disorders. Risks and side-effects are minimal, according to my reading of existing evidence, particularly at doses of 5 grams per day or less (see this risk assessment review: http://www.ncbi.nlm.nih.gov/pubmed/16814437 ). In the brain, the mechanism is of improving ATP availability, thereby improving cellular energy dynamics. Humans obtain creatine from the diet (about 1 g/day) and from synthesis inside the body (another 1 g/day). So it makes sense to have therapeutic doses well above the body's baseline supply of 2 g/day. Here is a reference to an excellent review article by Persky (2001 http://www.ncbi.nlm.nih.gov/pubmed/11356982
Creatine is readily available wherever one would obtain nutritional supplements. If one were to try creatine, I might suggest looking for pure creatine monohydrate, as opposed to some mixture (typically with protein powder), as the mixture would be more expensive, and would often contain unnecessary additives such as artificial sweeteners. The creatine could be ingested as a partially dissolved suspension in warm water or juice. The dosing regime could be debated somewhat, as creatine has quite a short half-life in plasma. This current study used a single large dose daily, but the idea of using divided dosing should be explored.
An augmentation refers to adding some type of therapeutic agent (usually a medication) to help make another therapeutic modality work better. Usually an augmentation would not be expected to help much on its own--the term implies that it must be used with something else. Typical augmentations in common use are triiodothyronine (a form of thyroid hormone) or lithium added to antidepressants to treat depression.
It's always nice to see an article which has an extremely simple premise (e.g. to try some new therapy or other), which could be readily applied in an attempt to help someone immediately.
The first article is from a Korean group (Lyoo et al.) published in the American Journal of Psychiatry in September 2012. ( http://www.ncbi.nlm.nih.gov/pubmed/22864465 ) They looked at treating 52 women having a major depressive episode, with either escitalopram 10-20 mg/day plus placebo, or escitalopram 10-20 mg plus 5 grams of creatine monohydrate daily.
From the second week of treatment onwards, the creatine group had better symptom improvement. After 8 weeks, over 50% of the creatine group met criteria for remission, compared to only about 25% of the placebo group.
Creatine has been used for years as a type of muscle-building supplement. It may have some benefits for various neuromuscular and other neurological disorders. Risks and side-effects are minimal, according to my reading of existing evidence, particularly at doses of 5 grams per day or less (see this risk assessment review: http://www.ncbi.nlm.nih.gov/pubmed/16814437 ). In the brain, the mechanism is of improving ATP availability, thereby improving cellular energy dynamics. Humans obtain creatine from the diet (about 1 g/day) and from synthesis inside the body (another 1 g/day). So it makes sense to have therapeutic doses well above the body's baseline supply of 2 g/day. Here is a reference to an excellent review article by Persky (2001 http://www.ncbi.nlm.nih.gov/pubmed/11356982
Creatine is readily available wherever one would obtain nutritional supplements. If one were to try creatine, I might suggest looking for pure creatine monohydrate, as opposed to some mixture (typically with protein powder), as the mixture would be more expensive, and would often contain unnecessary additives such as artificial sweeteners. The creatine could be ingested as a partially dissolved suspension in warm water or juice. The dosing regime could be debated somewhat, as creatine has quite a short half-life in plasma. This current study used a single large dose daily, but the idea of using divided dosing should be explored.
Monday, February 6, 2012
Scopolamine for Depression
Scopolamine is an acetylcholine-receptor blocker, which is usually used to treat or prevent motion sickness. Some recent studies show that it might be useful to treat depression. Here is some background, followed by a few references to research studies:
The old tricyclic antidepressants (such as amitriptyline) were shown over many years to work very well for many people. Unfortunately, they are laden with side-effect problems and a significant toxicity risk (they can be lethal in overdose). The side effects are due to various different pharmacologic effects, particularly the blockade of acetylcholine and histamine receptors. Newer antidepressants, such as those in the SSRI group, have very few such receptor blockade effects.
In some studies, however, the old tricyclics actually are superior to newer antidepressants, especially for severely ill hospitalized depression patients.
It is interesting to consider whether some of the receptor blockade effects which were previously considered just nuisances or side-effect problems, could actually be part of the antidepressant activity. Or, in some cases, drugs which primarily have receptor blockade side effects may actually be indirectly modulating various other neurotransmitter systems.
A clear precedent exists in this regard: clozapine is undoubtedly the most effective antipsychotic, but it is loaded with multiple side effects and receptor blockades. It may be --at least in part-- because of the receptor blockades, not in spite of them, that it works so well.
Another example of this effect, quite possibly, is related to what I call the "active placebo" literature (I have referred to it elsewhere on this blog: http://garthkroeker.blogspot.com/2009/03/active-placebos.html) The active placebos used in these studies usually had side effects due to acetylcholine blockade, and the active placebo groups usually improved quite a bit more than those with inert placebos. This suggests another interpretation of the "active placebo" effect: perhaps it is not simply the existence of side-effects that psychologically boosts a placebo effect here, it is that the side-effects themselves are due to a pharmacologic action that is actually of direct relevance to the treatment of depression.
Here are some studies looking at scopolamine infusions to treat depression:
http://www.ncbi.nlm.nih.gov/pubmed/17015814
This 2006 study from Archives of General Psychiatry showed that 4 mcg/kg IV infusions of scopolamine (given in 3 doses, every 3-5 days) led to a rapid reduction in depression symptoms (halving of the MADRS score), with a pronounced difference from placebo. Of particular note is that the cohort consisted mainly of chronically depressed patients with comorbidities and unsuccessful trials of other treatments. Surprisingly, there were few side effect problems, aside from a higher rate of the expected anticholinergic-induced dry mouth and dizziness.
http://www.ncbi.nlm.nih.gov/pubmed/20074703
This is a replication of the study mentioned above, published in Biological Psychiatry in 2010.
http://www.ncbi.nlm.nih.gov/pubmed/20736989
Another similar study, this time showing a greater effect in women; again a 4 mcg/kg infusion protocol was used.
http://www.ncbi.nlm.nih.gov/pubmed/20926947
evidence from an animal study that scopolamine --or acetylcholine blockade in general-- affects NMDA-related activity, in general antagonizing the effects of NMDA. This is consistent with a theory that scopolamine may work in a similar manner to the NMDA-blocker ketamine (which has been associated with rapid improvement in depression symptoms) but without nearly as much risk of dangerous medical or neuropsychiatric side-effects.
http://www.ncbi.nlm.nih.gov/pubmed/21306419
This article looks at the pharmacokinetics of infused scopolamine, and also gives a detailed account of side-effects. There are notable cognitive side-effects, such as reduced efficiency of short-term memory.
http://www.ncbi.nlm.nih.gov/pubmed/16719539
This study looks at dosing scopolamine as a patch. The patch is designed to give a rapidly absorbed loading dose, then a gradual release to maintain a fairly constant level over 3 days. My own estimation, based on reviewing this information, is that a scopolamine patch would roughly approximate the IV doses used in the depression treatment studies described above, though of course the serum levels would be more constant.
Transdermal scopolamine (patches) are available in Canada from pharmacists without a physician's prescription.
While this is an interesting--though far from proven-- treatment idea, it is very important to be aware of anticholinergic side effects, which at times could be physically and psychologically unpleasant. At worst, cognitive impairment or delirium could occur as a result of excessive cholinergic blockade. Therefore, any attempt to treat psychiatric symptoms using anticholinergics should be undertaken with close collaboration with a psychiatrist.
The old tricyclic antidepressants (such as amitriptyline) were shown over many years to work very well for many people. Unfortunately, they are laden with side-effect problems and a significant toxicity risk (they can be lethal in overdose). The side effects are due to various different pharmacologic effects, particularly the blockade of acetylcholine and histamine receptors. Newer antidepressants, such as those in the SSRI group, have very few such receptor blockade effects.
In some studies, however, the old tricyclics actually are superior to newer antidepressants, especially for severely ill hospitalized depression patients.
It is interesting to consider whether some of the receptor blockade effects which were previously considered just nuisances or side-effect problems, could actually be part of the antidepressant activity. Or, in some cases, drugs which primarily have receptor blockade side effects may actually be indirectly modulating various other neurotransmitter systems.
A clear precedent exists in this regard: clozapine is undoubtedly the most effective antipsychotic, but it is loaded with multiple side effects and receptor blockades. It may be --at least in part-- because of the receptor blockades, not in spite of them, that it works so well.
Another example of this effect, quite possibly, is related to what I call the "active placebo" literature (I have referred to it elsewhere on this blog: http://garthkroeker.blogspot.com/2009/03/active-placebos.html) The active placebos used in these studies usually had side effects due to acetylcholine blockade, and the active placebo groups usually improved quite a bit more than those with inert placebos. This suggests another interpretation of the "active placebo" effect: perhaps it is not simply the existence of side-effects that psychologically boosts a placebo effect here, it is that the side-effects themselves are due to a pharmacologic action that is actually of direct relevance to the treatment of depression.
Here are some studies looking at scopolamine infusions to treat depression:
http://www.ncbi.nlm.nih.gov/pubmed/17015814
This 2006 study from Archives of General Psychiatry showed that 4 mcg/kg IV infusions of scopolamine (given in 3 doses, every 3-5 days) led to a rapid reduction in depression symptoms (halving of the MADRS score), with a pronounced difference from placebo. Of particular note is that the cohort consisted mainly of chronically depressed patients with comorbidities and unsuccessful trials of other treatments. Surprisingly, there were few side effect problems, aside from a higher rate of the expected anticholinergic-induced dry mouth and dizziness.
http://www.ncbi.nlm.nih.gov/pubmed/20074703
This is a replication of the study mentioned above, published in Biological Psychiatry in 2010.
http://www.ncbi.nlm.nih.gov/pubmed/20736989
Another similar study, this time showing a greater effect in women; again a 4 mcg/kg infusion protocol was used.
http://www.ncbi.nlm.nih.gov/pubmed/20926947
evidence from an animal study that scopolamine --or acetylcholine blockade in general-- affects NMDA-related activity, in general antagonizing the effects of NMDA. This is consistent with a theory that scopolamine may work in a similar manner to the NMDA-blocker ketamine (which has been associated with rapid improvement in depression symptoms) but without nearly as much risk of dangerous medical or neuropsychiatric side-effects.
http://www.ncbi.nlm.nih.gov/pubmed/21306419
This article looks at the pharmacokinetics of infused scopolamine, and also gives a detailed account of side-effects. There are notable cognitive side-effects, such as reduced efficiency of short-term memory.
http://www.ncbi.nlm.nih.gov/pubmed/16719539
This study looks at dosing scopolamine as a patch. The patch is designed to give a rapidly absorbed loading dose, then a gradual release to maintain a fairly constant level over 3 days. My own estimation, based on reviewing this information, is that a scopolamine patch would roughly approximate the IV doses used in the depression treatment studies described above, though of course the serum levels would be more constant.
Transdermal scopolamine (patches) are available in Canada from pharmacists without a physician's prescription.
While this is an interesting--though far from proven-- treatment idea, it is very important to be aware of anticholinergic side effects, which at times could be physically and psychologically unpleasant. At worst, cognitive impairment or delirium could occur as a result of excessive cholinergic blockade. Therefore, any attempt to treat psychiatric symptoms using anticholinergics should be undertaken with close collaboration with a psychiatrist.
Thursday, December 22, 2011
Antidepressants = Psychotherapy = Placebo ?
Jacques Barber et al. have recently published the results of a randomized, controlled study conducted between 2001 and 2007, comparing antidepressant therapy, short-term dynamic psychotherapy, and placebo in a 16-week course of treatment for 156 depressed adults. Here is a link to the abstract: http://www.ncbi.nlm.nih.gov/pubmed/22152401
The bottom line in the study was that there was no significant difference between antidepressants, psychotherapy, or placebo. Response rates were 31% for medication, 28% for psychotherapy, and 24% for placebo -- which has a low probability of being statistically different. Remission rates were 26% for medication, 22% for psychotherapy, and 20% for placebo.
Critics trying to explain these findings might attempt to argue that the psychotherapy or the medication regime was not sufficient, etc. -- but I do not see this to be true. The medications (venlafaxine or sertraline) were given at quite sufficient doses for good lengths of time. The psychotherapy was not CBT (which has a larger research evidence base) but there is little reason, in my opinion, to believe that the therapy style was inferior.
The authors attempt to do some secondary analyses looking for explanations, but their conclusions seem quite weak to me (e.g. regarding race or gender). The fact that they spin these conclusions into a prominently framed set of "clinical points" seems quite inappropriate to me -- this is a negative study, there are no "clinical points" to be found here, unless they recommend placebos and cessation of other therapies!
There are a number of issues from this study that I do find very important to discuss:
1) despite a massive amount of data showing that various therapies (e.g. antidepressants or psychotherapy) are effective for various problems, there are examples of carefully-conducted negative studies, such as this one. These results cannot simply be explained away as statistical aberration: there must be a reason why one group of people responds to a treatment, while another does not. Many of these reasons are poorly understood. It may be that the diagnostic category of "major depressive disorder" is inadequate, in that it correlates poorly on its own with treatment responsiveness.
2) the subjects in this study had a high degree of comorbidity (e.g. substance abuse problems, anxiety disorders, and axis II problems). While the severity and chronicity of depression was not found to actually correlate with treatment responsiveness, I suspect that the comorbidities would substantially affect response to a relatively short-term course of therapy.
3) the subjects in this study were socioeconomically disadvantaged; while the effect of SES was also not found to "influence the initial findings," I believe that low SES is not necessarily a direct negative influence upon mental health; rather it is an indirect factor which for many people increases the likelihood of some profound mental health negatives (e.g. unemployment, lack of meaningful or satisfying employment, lack of healthy or safe community, lack of availability to do healthy or meaningful leisure activities, not enough money to eat healthily, etc.). I believe that the environmental adversities need to be looked at very closely in a study of this type.
This leads to what I believe is an obvious explanation for the findings here: there is no therapy for depression that is likely to help unless ALL contributing factors (including obvious environmental contributing factors) are addressed. By way of analogy, I believe it is pointless to treat insomnia using a powerful sedative if a person is sleeping in a room which is continuously noisy, cold, and prone to break-ins by violent intruders. The environmental issues need to be addressed first! Another analogy I have often used is of trying to repair a water supply system for a city: it is a waste of effort to pipe in more water from rivers, or to dig a deeper reservoir, if the walls of the reservoir and the pipes are leaking or bursting because of structural defects. In order for a therapeutic strategy to work, the "leaks" have to be repaired first. For a person with anemia, it is not an appropriate strategy to simply give a blood transfusion: while a transfusion may be necessary, it will not be sufficient--and could even make matters worse-- if the underlying cause of blood loss is not addressed and treated.
In the case of medications or psychotherapy, I believe these can be very helpful, but only if environmental adversity is also remedied. In some instances, of course, relief of a psychiatric symptom could help a person to improve the environmental circumstances. But in most other cases, I think the issue is broader, and could be considered a political or social policy matter.
Another related issue is that I do not believe "depression" can be treated on its own without addressing all psychiatric and medical comorbidities at the same time. Ongoing substance abuse, in my opinion, is often a powerful enough factor--psychologically as well as neurophysiologically--to completely dominate and dissolve the positive influences of psychotherapy or effective medication. In this study, 30-40% of the cohort reported substance use problems.
As a final thought, I think the "5 axis" model of diagnosis in the DSM system deserves some affirmation; many times, however, we only pay attention to Axis I (diagnoses such as depression or schizophrenia, etc.) or Axis II (personality disorder). I think that studies such as this one highlight the necessity to look closely at Axes III (medical illnesses) and IV (social, community, financial, and relational problems). It is likely that issues on these latter two axes can prevent any resolution of problems on the first two.
The bottom line in the study was that there was no significant difference between antidepressants, psychotherapy, or placebo. Response rates were 31% for medication, 28% for psychotherapy, and 24% for placebo -- which has a low probability of being statistically different. Remission rates were 26% for medication, 22% for psychotherapy, and 20% for placebo.
Critics trying to explain these findings might attempt to argue that the psychotherapy or the medication regime was not sufficient, etc. -- but I do not see this to be true. The medications (venlafaxine or sertraline) were given at quite sufficient doses for good lengths of time. The psychotherapy was not CBT (which has a larger research evidence base) but there is little reason, in my opinion, to believe that the therapy style was inferior.
The authors attempt to do some secondary analyses looking for explanations, but their conclusions seem quite weak to me (e.g. regarding race or gender). The fact that they spin these conclusions into a prominently framed set of "clinical points" seems quite inappropriate to me -- this is a negative study, there are no "clinical points" to be found here, unless they recommend placebos and cessation of other therapies!
There are a number of issues from this study that I do find very important to discuss:
1) despite a massive amount of data showing that various therapies (e.g. antidepressants or psychotherapy) are effective for various problems, there are examples of carefully-conducted negative studies, such as this one. These results cannot simply be explained away as statistical aberration: there must be a reason why one group of people responds to a treatment, while another does not. Many of these reasons are poorly understood. It may be that the diagnostic category of "major depressive disorder" is inadequate, in that it correlates poorly on its own with treatment responsiveness.
2) the subjects in this study had a high degree of comorbidity (e.g. substance abuse problems, anxiety disorders, and axis II problems). While the severity and chronicity of depression was not found to actually correlate with treatment responsiveness, I suspect that the comorbidities would substantially affect response to a relatively short-term course of therapy.
3) the subjects in this study were socioeconomically disadvantaged; while the effect of SES was also not found to "influence the initial findings," I believe that low SES is not necessarily a direct negative influence upon mental health; rather it is an indirect factor which for many people increases the likelihood of some profound mental health negatives (e.g. unemployment, lack of meaningful or satisfying employment, lack of healthy or safe community, lack of availability to do healthy or meaningful leisure activities, not enough money to eat healthily, etc.). I believe that the environmental adversities need to be looked at very closely in a study of this type.
This leads to what I believe is an obvious explanation for the findings here: there is no therapy for depression that is likely to help unless ALL contributing factors (including obvious environmental contributing factors) are addressed. By way of analogy, I believe it is pointless to treat insomnia using a powerful sedative if a person is sleeping in a room which is continuously noisy, cold, and prone to break-ins by violent intruders. The environmental issues need to be addressed first! Another analogy I have often used is of trying to repair a water supply system for a city: it is a waste of effort to pipe in more water from rivers, or to dig a deeper reservoir, if the walls of the reservoir and the pipes are leaking or bursting because of structural defects. In order for a therapeutic strategy to work, the "leaks" have to be repaired first. For a person with anemia, it is not an appropriate strategy to simply give a blood transfusion: while a transfusion may be necessary, it will not be sufficient--and could even make matters worse-- if the underlying cause of blood loss is not addressed and treated.
In the case of medications or psychotherapy, I believe these can be very helpful, but only if environmental adversity is also remedied. In some instances, of course, relief of a psychiatric symptom could help a person to improve the environmental circumstances. But in most other cases, I think the issue is broader, and could be considered a political or social policy matter.
Another related issue is that I do not believe "depression" can be treated on its own without addressing all psychiatric and medical comorbidities at the same time. Ongoing substance abuse, in my opinion, is often a powerful enough factor--psychologically as well as neurophysiologically--to completely dominate and dissolve the positive influences of psychotherapy or effective medication. In this study, 30-40% of the cohort reported substance use problems.
As a final thought, I think the "5 axis" model of diagnosis in the DSM system deserves some affirmation; many times, however, we only pay attention to Axis I (diagnoses such as depression or schizophrenia, etc.) or Axis II (personality disorder). I think that studies such as this one highlight the necessity to look closely at Axes III (medical illnesses) and IV (social, community, financial, and relational problems). It is likely that issues on these latter two axes can prevent any resolution of problems on the first two.
Thursday, November 3, 2011
Piracetam
Piracetam is a so-called "nootropic" drug, a substance which supposedly helps improve cognitive functioning. It is available without prescription as a sort of supplement in many parts of the world. In Canada it is not illegal, but must be imported (such as by ordering over the internet from U.S. suppliers).
The mechanism of action is not clear. There is no obvious single receptor-mediated mechanism. There may be various effects on ion channels, cell membrane characteristics, etc. but of course such statements are quite vague.
It is quite clear that there are few side-effect problems or toxicity risks with this agent. Doses are typically 2-5 grams per day.
I became interested in this agent after encountering a case example of someone who reported quite a dramatic improvement in mood and overall functioning attributed to piracetam supplementation.
Here are the results of my survey through the research literature:
http://www.ncbi.nlm.nih.gov/pubmed/16007238 -- a 2005 review
http://www.ncbi.nlm.nih.gov/pubmed/1794001 -- a 1991 review looking specifically at its use in treating dementia; the data is really not impressive at all for dementia treatment.
http://www.ncbi.nlm.nih.gov/pubmed/11084917 -- a 2000 Japanese study affirming the effectiveness of piracetam combined with clonazepam for treating myoclonus (myoclonus is a neurological problem in which muscles are twitching involuntarily).
http://www.ncbi.nlm.nih.gov/pubmed/8914096 -- a 1996 study from Japan also showing benefit in treating myoclonus; there were also improvements in motivation, attention, sleep, and mood (possibly secondary to improvement in the movement disorder).
http://www.ncbi.nlm.nih.gov/pubmed/11346373 -- 2001 study from Archives of Neurology again affirming that piracetam is effective over 12 months of follow-up for treating myoclonic epilepsy.
http://www.ncbi.nlm.nih.gov/pubmed/10796585 -- this 2000 Cochrane review stated that the data on piracetam are inconclusive, with studies not being of good quality
http://www.ncbi.nlm.nih.gov/pubmed/10338110 - this 1999 article reviewed studies of piracetam for treating vertigo, concluding that it was useful for reducing frequency of recurrence, at doses of 2-5 grams per day.
http://www.ncbi.nlm.nih.gov/pubmed/17685739 -- this is a 2007 randomized placebo-controlled study from The Journal of Clinical Psychiatry, in which piracetam 4800 mg/d for 9 weeks led to substantial improvements in tardive dyskinesia, with large differences from placebo.
http://www.ncbi.nlm.nih.gov/pubmed/10338108 -- piracetam has some antiplatelet function, which could be used in managing or preventing recurrences of vascular disorders. This is a 1999 review of this subject.
http://www.ncbi.nlm.nih.gov/pubmed/8061686 -- this is a broad review of nootropics, published in 1994.
http://www.ncbi.nlm.nih.gov/pubmed/3305591 -- this 1987 study from The Journal of Clinical Psychopharmacology shows that children treated with piracetam may show improvements in dyslexia.
Doses were 3.3 grams daily x 36 weeks (dosed twice per day). However, as I look at the results, I see that there is a statistical difference, but the numbers really look very similar between placebo and piracetam. The placebo group improved substantially; the piracetam group improved only slightly more. For example, the raw scores in the Grey Oral Reading Test increased from 17.1 to 22.5 in the placebo group; in the piracetam group it increased from 14.8 to 22.9. It is true that the piracetam was well-tolerated, with minimal side-effect problems.
http://www.ncbi.nlm.nih.gov/pubmed/12394531
this is a 2002 study which attempted to show whether piracetam could prevent ECT-induced cognitive problems. The dose was 7.2 g/day for a 2-week loading phase, then 4.8 g daily for the remaining 2 weeks. They concluded that piracetam had no effect on cognition in this group; but the piracetam group did slightly better than the placebo group in terms of overall clinical improvement.
http://www.ncbi.nlm.nih.gov/pubmed/16878489
this 2006 study described anxiolytic effects of piracetam which were blocked by flumazenil (a benzodiazepine receptor blocker), suggesting that piracetam has some GABA-like activity.
http://www.ncbi.nlm.nih.gov/pubmed/12809069
a Hungarian study describing successful use of piracetam to treat alcohol withdrawal delirium
http://www.ncbi.nlm.nih.gov/pubmed/7906672
a 1993 Indian study showing that piracetam has anti-anxiety effects when administered on a longer-term basis in rats.
http://www.ncbi.nlm.nih.gov/pubmed/95599
a 1979 article from Journal of Affective Disorders describing anti-anxiety effects from piracetam similar to a benzodiazepine, but without sedation.
http://www.ncbi.nlm.nih.gov/pubmed/6415738
in this 1983 study, piracetam 2.4 g/day or 4.8 g/day was compared with placebo in treating 60 elderly psychiatric patients; the 2.4 g/day group showed increased socialization, altertness, and cooperation, and had some improvement on memory and IQ tests, compared to the placebo group.
http://www.ncbi.nlm.nih.gov/pubmed/360232
in this 1977 study, elderly psychiatric patients were given 2.4 g/day of piracetam or placebo, for 2 months. The piracetam group did not improve in any cognitive tests or mood symptom scores compared to placebo, but interestingly 52% of subjects in the piracetam group showed overall improvement (CGI) compared to only 25% in the placebo group.
http://www.ncbi.nlm.nih.gov/pubmed/11687079
a Cochrane review from 2001 concluding that there is evidence that piracetam may improve the course of aphasia after stroke; however, the evidence was found to be weak.
http://www.ncbi.nlm.nih.gov/pubmed/6128331
this 1982 study shows that 40 g of IV piracetam caused greater reduction than placebo in antipsychotic-induced Parkinsonian side-effects.
http://www.ncbi.nlm.nih.gov/pubmed/488520
a small 1979 study which showed that refractory depressed patients improved with the addition of 2.4 g piracetam.
http://www.ncbi.nlm.nih.gov/pubmed/10338106
a look at toxicity risk due to piracetam, when given in higher doses (12 g/day) for 12 weeks, to stroke patients. The paper concludes that there is no significant toxicity risk at this dose for this population.
In conclusion, piracetam appears to be clearly effective for a few uncommon conditions, such as myoclonus. There is possible effectiveness for some other problems such as tardive dyskinesia. The evidence for effectiveness as a "cognitive enhancer" appears to be quite shaky, but not absent.
I am particularly interested in some of the evidence which suggests that it could be useful as a safe, well-tolerated adjunct to treat depression or anxiety. Some of the studies quoted above appear to support this possibility. This theme also intersects with my recent thoughts about considering cognitive function in chronic mood, anxiety, ADHD, or personality disorders. A weakness in working memory capacity or executive functioning could substantially interfere with recovery from psychiatric illness; I suspect that a treatment which could specifically help with cognitive function could be a unique angle to augment treatments for these other psychiatric problems. (see my previous post, which discusses an association between rumination & working memory dysfunction: http://garthkroeker.blogspot.com/2011/08/chronic-pain-rumination.html). Here's another link about this: http://www.ncbi.nlm.nih.gov/pubmed/21742932)
I do think it would be worthwhile for research groups to consider doing some new, careful, large trials of piracetam as an augmentation for managing depression, anxiety disorders, etc.
The mechanism of action is not clear. There is no obvious single receptor-mediated mechanism. There may be various effects on ion channels, cell membrane characteristics, etc. but of course such statements are quite vague.
It is quite clear that there are few side-effect problems or toxicity risks with this agent. Doses are typically 2-5 grams per day.
I became interested in this agent after encountering a case example of someone who reported quite a dramatic improvement in mood and overall functioning attributed to piracetam supplementation.
Here are the results of my survey through the research literature:
http://www.ncbi.nlm.nih.gov/pubmed/16007238 -- a 2005 review
http://www.ncbi.nlm.nih.gov/pubmed/1794001 -- a 1991 review looking specifically at its use in treating dementia; the data is really not impressive at all for dementia treatment.
http://www.ncbi.nlm.nih.gov/pubmed/11084917 -- a 2000 Japanese study affirming the effectiveness of piracetam combined with clonazepam for treating myoclonus (myoclonus is a neurological problem in which muscles are twitching involuntarily).
http://www.ncbi.nlm.nih.gov/pubmed/8914096 -- a 1996 study from Japan also showing benefit in treating myoclonus; there were also improvements in motivation, attention, sleep, and mood (possibly secondary to improvement in the movement disorder).
http://www.ncbi.nlm.nih.gov/pubmed/11346373 -- 2001 study from Archives of Neurology again affirming that piracetam is effective over 12 months of follow-up for treating myoclonic epilepsy.
http://www.ncbi.nlm.nih.gov/pubmed/10796585 -- this 2000 Cochrane review stated that the data on piracetam are inconclusive, with studies not being of good quality
http://www.ncbi.nlm.nih.gov/pubmed/10338110 - this 1999 article reviewed studies of piracetam for treating vertigo, concluding that it was useful for reducing frequency of recurrence, at doses of 2-5 grams per day.
http://www.ncbi.nlm.nih.gov/pubmed/17685739 -- this is a 2007 randomized placebo-controlled study from The Journal of Clinical Psychiatry, in which piracetam 4800 mg/d for 9 weeks led to substantial improvements in tardive dyskinesia, with large differences from placebo.
http://www.ncbi.nlm.nih.gov/pubmed/10338108 -- piracetam has some antiplatelet function, which could be used in managing or preventing recurrences of vascular disorders. This is a 1999 review of this subject.
http://www.ncbi.nlm.nih.gov/pubmed/8061686 -- this is a broad review of nootropics, published in 1994.
http://www.ncbi.nlm.nih.gov/pubmed/3305591 -- this 1987 study from The Journal of Clinical Psychopharmacology shows that children treated with piracetam may show improvements in dyslexia.
Doses were 3.3 grams daily x 36 weeks (dosed twice per day). However, as I look at the results, I see that there is a statistical difference, but the numbers really look very similar between placebo and piracetam. The placebo group improved substantially; the piracetam group improved only slightly more. For example, the raw scores in the Grey Oral Reading Test increased from 17.1 to 22.5 in the placebo group; in the piracetam group it increased from 14.8 to 22.9. It is true that the piracetam was well-tolerated, with minimal side-effect problems.
http://www.ncbi.nlm.nih.gov/pubmed/12394531
this is a 2002 study which attempted to show whether piracetam could prevent ECT-induced cognitive problems. The dose was 7.2 g/day for a 2-week loading phase, then 4.8 g daily for the remaining 2 weeks. They concluded that piracetam had no effect on cognition in this group; but the piracetam group did slightly better than the placebo group in terms of overall clinical improvement.
http://www.ncbi.nlm.nih.gov/pubmed/16878489
this 2006 study described anxiolytic effects of piracetam which were blocked by flumazenil (a benzodiazepine receptor blocker), suggesting that piracetam has some GABA-like activity.
http://www.ncbi.nlm.nih.gov/pubmed/12809069
a Hungarian study describing successful use of piracetam to treat alcohol withdrawal delirium
http://www.ncbi.nlm.nih.gov/pubmed/7906672
a 1993 Indian study showing that piracetam has anti-anxiety effects when administered on a longer-term basis in rats.
http://www.ncbi.nlm.nih.gov/pubmed/95599
a 1979 article from Journal of Affective Disorders describing anti-anxiety effects from piracetam similar to a benzodiazepine, but without sedation.
http://www.ncbi.nlm.nih.gov/pubmed/6415738
in this 1983 study, piracetam 2.4 g/day or 4.8 g/day was compared with placebo in treating 60 elderly psychiatric patients; the 2.4 g/day group showed increased socialization, altertness, and cooperation, and had some improvement on memory and IQ tests, compared to the placebo group.
http://www.ncbi.nlm.nih.gov/pubmed/360232
in this 1977 study, elderly psychiatric patients were given 2.4 g/day of piracetam or placebo, for 2 months. The piracetam group did not improve in any cognitive tests or mood symptom scores compared to placebo, but interestingly 52% of subjects in the piracetam group showed overall improvement (CGI) compared to only 25% in the placebo group.
http://www.ncbi.nlm.nih.gov/pubmed/11687079
a Cochrane review from 2001 concluding that there is evidence that piracetam may improve the course of aphasia after stroke; however, the evidence was found to be weak.
http://www.ncbi.nlm.nih.gov/pubmed/6128331
this 1982 study shows that 40 g of IV piracetam caused greater reduction than placebo in antipsychotic-induced Parkinsonian side-effects.
http://www.ncbi.nlm.nih.gov/pubmed/488520
a small 1979 study which showed that refractory depressed patients improved with the addition of 2.4 g piracetam.
http://www.ncbi.nlm.nih.gov/pubmed/10338106
a look at toxicity risk due to piracetam, when given in higher doses (12 g/day) for 12 weeks, to stroke patients. The paper concludes that there is no significant toxicity risk at this dose for this population.
In conclusion, piracetam appears to be clearly effective for a few uncommon conditions, such as myoclonus. There is possible effectiveness for some other problems such as tardive dyskinesia. The evidence for effectiveness as a "cognitive enhancer" appears to be quite shaky, but not absent.
I am particularly interested in some of the evidence which suggests that it could be useful as a safe, well-tolerated adjunct to treat depression or anxiety. Some of the studies quoted above appear to support this possibility. This theme also intersects with my recent thoughts about considering cognitive function in chronic mood, anxiety, ADHD, or personality disorders. A weakness in working memory capacity or executive functioning could substantially interfere with recovery from psychiatric illness; I suspect that a treatment which could specifically help with cognitive function could be a unique angle to augment treatments for these other psychiatric problems. (see my previous post, which discusses an association between rumination & working memory dysfunction: http://garthkroeker.blogspot.com/2011/08/chronic-pain-rumination.html). Here's another link about this: http://www.ncbi.nlm.nih.gov/pubmed/21742932)
I do think it would be worthwhile for research groups to consider doing some new, careful, large trials of piracetam as an augmentation for managing depression, anxiety disorders, etc.
Monday, January 10, 2011
Reading Exercises
A common problem I find among university students is difficulty reading quickly or efficiently. Reading problems can also occur in conjunction with depression.
The best thing to do to improve reading skills is, of course, to read more. But a phenomenon which often happens when reading any text, but especially longer texts, such as novels, is that you can lose track of what you have just been reading. Whole sections of the text may end up being skimmed superficially, as part of your attention lapses or wanders, while still maintaining a basic pace of absent-minded reading. This leads to a lack of enjoyment or feeling of mastery with reading, dampened morale, sapped motivation, contributing further to any depression which had been present, and deterring further reading efforts.
An approach to this type of problem requires you to stop to reflect or answer questions frequently about what you have just read. Whenever you test yourself regularly, your learning and retention are greatly increased. Most good introductory university textbooks are set up this way. But not very much in the line of non-textbook reading.
So, I have been trying to find resources to help with reading skill, for adults. Elementary-school language textbooks or readers seemed like a reasonable thing to check. I certainly recommend that adults at least periodically read books which have been written for children or adolescents. The best things I've found online are from ESL (English as a second language) programs. Even if you are an advanced reader, or have spoken English all your life, I think that ESL exercises could be good for improving reading skill.
Cognitive-skills training websites tend not to offer very much in terms of language learning or improving reading fluency or retention. I wish that the cognitive skills website people could develop more along these lines: reading-oriented games don't seem very difficult to imagine or design, compared to other types of games.
Here's a list of a few sites I've found, where you can practice English reading skills:
http://web2.uvcs.uvic.ca/courses/elc/studyzone/
This is an excellent free resource from the University of Victoria (in BC). For the reading exercises, choose an "English language level" (beginner to advanced), then follow the links about reading.
Houghton Mifflin College
This site also offers timed readings with questions afterwards.
Quizzes Based On VOA Programs (ESL/EFL)
This link goes to a site where you have to read a text a sentence at a time, and fill in the blanks from a list of options, according to what makes sense or is grammatically correct. While some might find this type of exercise too easy, I think it is a nice way to remain more interactive with the text. If you do find it easy, you can just try to do it faster, and make it into a game.
Another useful thing to look for is an online book club which has discussion questions about the book you're reading. Some sites have questions for each chapter, which is the type of thing I'm recommending, so that you can pause frequently to review what you have just been reading. I haven't found a single site which has chapter-by-chapter questions for a wide variety of books, but here's an example of a specific site, giving questions about Great Expectations by Charles Dickens (a great book, by the way):
http://www.victorianweb.org/authors/dickens/ge/pva107.html
The best thing to do to improve reading skills is, of course, to read more. But a phenomenon which often happens when reading any text, but especially longer texts, such as novels, is that you can lose track of what you have just been reading. Whole sections of the text may end up being skimmed superficially, as part of your attention lapses or wanders, while still maintaining a basic pace of absent-minded reading. This leads to a lack of enjoyment or feeling of mastery with reading, dampened morale, sapped motivation, contributing further to any depression which had been present, and deterring further reading efforts.
An approach to this type of problem requires you to stop to reflect or answer questions frequently about what you have just read. Whenever you test yourself regularly, your learning and retention are greatly increased. Most good introductory university textbooks are set up this way. But not very much in the line of non-textbook reading.
So, I have been trying to find resources to help with reading skill, for adults. Elementary-school language textbooks or readers seemed like a reasonable thing to check. I certainly recommend that adults at least periodically read books which have been written for children or adolescents. The best things I've found online are from ESL (English as a second language) programs. Even if you are an advanced reader, or have spoken English all your life, I think that ESL exercises could be good for improving reading skill.
Cognitive-skills training websites tend not to offer very much in terms of language learning or improving reading fluency or retention. I wish that the cognitive skills website people could develop more along these lines: reading-oriented games don't seem very difficult to imagine or design, compared to other types of games.
Here's a list of a few sites I've found, where you can practice English reading skills:
http://web2.uvcs.uvic.ca/courses/elc/studyzone/
This is an excellent free resource from the University of Victoria (in BC). For the reading exercises, choose an "English language level" (beginner to advanced), then follow the links about reading.
Houghton Mifflin College
This site also offers timed readings with questions afterwards.
Quizzes Based On VOA Programs (ESL/EFL)
This link goes to a site where you have to read a text a sentence at a time, and fill in the blanks from a list of options, according to what makes sense or is grammatically correct. While some might find this type of exercise too easy, I think it is a nice way to remain more interactive with the text. If you do find it easy, you can just try to do it faster, and make it into a game.
Another useful thing to look for is an online book club which has discussion questions about the book you're reading. Some sites have questions for each chapter, which is the type of thing I'm recommending, so that you can pause frequently to review what you have just been reading. I haven't found a single site which has chapter-by-chapter questions for a wide variety of books, but here's an example of a specific site, giving questions about Great Expectations by Charles Dickens (a great book, by the way):
http://www.victorianweb.org/authors/dickens/ge/pva107.html
Friday, July 16, 2010
Dopamine Agonists in Psychiatry
The dopamine agonists pramipexole and ropinirole are drugs used in the treatment of Parkinson Disease.
These drugs are now well-established in treating restless legs syndrome (RLS) and periodic limb movement disorder of sleep (PLMS), which are frequent problems afflicting about 10% of the population, and which can negatively impact quality of life & mood symptoms.
There is a small body of evidence showing possible benefits of dopamine agonists in the treatment of depression.
Unfortunately, dopamine agonists can exacerbate addictive/compulsive behaviour: http://www.ncbi.nlm.nih.gov/pubmed/20484726
Here are some references about the role of dopamine agonists in RLS and PLMS:
http://www.ncbi.nlm.nih.gov/pubmed/20120624
Here's a good review article on the use of ropinirole to treat these conditions: http://www.ncbi.nlm.nih.gov/pubmed/20421915
Here's a recent review of dopamine agonists in general to treat RLS: http://www.ncbi.nlm.nih.gov/pubmed/20206780
Here's a 2008 meta-analysis comparing ropinirole with pramipexole for treating RLS. Pramipexole is shown to be slightly superior:
http://www.ncbi.nlm.nih.gov/pubmed/18226947
In this 2010 study, gabapentin was compared to ropinirole for treating RLS. While ropinirole was superior in reducing objective measures of periodic limb movements, subjects taking gabapentin had a higher subjective benefit:
http://www.ncbi.nlm.nih.gov/pubmed/20049491
Here's a case study showing remission of depressive symptoms with ropinirole used as an augmenting agent:
http://www.ncbi.nlm.nih.gov/pubmed/20188777
Here's a 2005 study looking at ropinirole augmentation in treating depression:
http://www.ncbi.nlm.nih.gov/pubmed/15999953
This 2010 review in Lancet showed a direct antidepressant effect of pramipexole in Parkinson Disease patients: http://www.ncbi.nlm.nih.gov/pubmed/20452823
Here's a rather weak but positive 2010 paper describing a group of patients with bipolar depression who appeared to benefit from longer-term pramipexole treatment; doses averaged about 1 mg/d: http://www.ncbi.nlm.nih.gov/pubmed/20425143
The side effects from these drugs include frequent nausea and dizziness, possibly some daytime sleepiness. Psychiatric adverse effects can include hallucinations, and increased compulsive or impulse-control problems.
In summary, I think dopamine agonists have a role in selected psychiatric conditions, particularly if there are restless-legs symptoms contributing to insomnia or nocturnal discomfort. They may help treat refractory depression, but there is a risk of causing impulse control problems or hallucinations in predisposed individuals.
These drugs are now well-established in treating restless legs syndrome (RLS) and periodic limb movement disorder of sleep (PLMS), which are frequent problems afflicting about 10% of the population, and which can negatively impact quality of life & mood symptoms.
There is a small body of evidence showing possible benefits of dopamine agonists in the treatment of depression.
Unfortunately, dopamine agonists can exacerbate addictive/compulsive behaviour: http://www.ncbi.nlm.nih.gov/pubmed/20484726
Here are some references about the role of dopamine agonists in RLS and PLMS:
http://www.ncbi.nlm.nih.gov/pubmed/20120624
Here's a good review article on the use of ropinirole to treat these conditions: http://www.ncbi.nlm.nih.gov/pubmed/20421915
Here's a recent review of dopamine agonists in general to treat RLS: http://www.ncbi.nlm.nih.gov/pubmed/20206780
Here's a 2008 meta-analysis comparing ropinirole with pramipexole for treating RLS. Pramipexole is shown to be slightly superior:
http://www.ncbi.nlm.nih.gov/pubmed/18226947
In this 2010 study, gabapentin was compared to ropinirole for treating RLS. While ropinirole was superior in reducing objective measures of periodic limb movements, subjects taking gabapentin had a higher subjective benefit:
http://www.ncbi.nlm.nih.gov/pubmed/20049491
Here's a case study showing remission of depressive symptoms with ropinirole used as an augmenting agent:
http://www.ncbi.nlm.nih.gov/pubmed/20188777
Here's a 2005 study looking at ropinirole augmentation in treating depression:
http://www.ncbi.nlm.nih.gov/pubmed/15999953
This 2010 review in Lancet showed a direct antidepressant effect of pramipexole in Parkinson Disease patients: http://www.ncbi.nlm.nih.gov/pubmed/20452823
Here's a rather weak but positive 2010 paper describing a group of patients with bipolar depression who appeared to benefit from longer-term pramipexole treatment; doses averaged about 1 mg/d: http://www.ncbi.nlm.nih.gov/pubmed/20425143
The side effects from these drugs include frequent nausea and dizziness, possibly some daytime sleepiness. Psychiatric adverse effects can include hallucinations, and increased compulsive or impulse-control problems.
In summary, I think dopamine agonists have a role in selected psychiatric conditions, particularly if there are restless-legs symptoms contributing to insomnia or nocturnal discomfort. They may help treat refractory depression, but there is a risk of causing impulse control problems or hallucinations in predisposed individuals.
Monday, February 1, 2010
Self-help books
There are a lot of self-help books to choose from, dealing with almost anything including mood problems, anger, anxiety, body image, obesity, shyness, relationship or marriage problems, etc.
There are others that might aim to help a person develop creativity, or guide one with respect to some other life pursuit, such as building a sense of purpose, meaning, balance, simplicity, etc.
I think it is worthwhile to familiarize yourself with the self-help literature. I think it can be something like getting a textbook for a course at school...while some textbooks may not be very well-written, I think having a textbook at all can at least allow some extra tangible structure in therapeutic work.
Most self-help books have exercises to work through, often requiring you to write things out with pen and paper. I think it is important to actually do the exercises, as opposed to just leafing through the book, or thinking that you've done all those things in your mind before anyway. Working through exercises strengthens the mind, even if the exercises themselves are not very well-constructed. It is something like working through arithmetic or grammar problems. Even if the exercises are boring or trite, the earnest effort spent working through them will strengthen your ability and insight about the subject matter. Also, most self-help books, even if they are poorly written, can act as structures to develop your own personalized insights about the subject matter--the workbooks can be a frame to do the work, as opposed to being an intrinsic source of insight.
Many self-help books are organized with cognitive-behavioural ideas in mind. Once again, even if you don't care much for cognitive therapy, the exercises remain useful, provided you engage in them earnestly (it is possible to do these exercises in a half-hearted or sarcastic way, etc. -- which would minimize any possible benefit, just as with any other exercise in life).
What does evidence have to say about self-help books? So-called "bibliotherapy" (yes, someone had to designate an awkward piece of vocabulary to describe "reading") has an evidence base--here are a few references:
Gregory et al. published this 2006 meta-analysis showing cognitive bibliotherapy was effective for depression: Professional Psychology: Research and Practice 2004, Vol. 35, No. 3, 275–280. They concluded that bibliotherapy had an effect size of about 0.77, which is substantial, and comparable to effect sizes from medications and psychotherapy.
Here is a reference to a 2003 meta-analysis by Newman et al. showing that bibliotherapy was effective in the treatment of various anxiety disorders:
http://www.ncbi.nlm.nih.gov/pubmed/12579544
Here is a 2004 reference showing that guided self-help is effective in treating bulimia:
http://www.ncbi.nlm.nih.gov/pubmed/15101068
In conclusion, I do strongly recommend working through self-help books. I find that it can be important to look at several different ones, as there can be style or content differences causing you to prefer one over the other.
The main word of caution I have about self-help is that some authors may have a very biased point of view (perhaps influenced by dogmatic or eccentric beliefs regarding politics, religion, health care, etc.), and may therefore lead a vulnerable individual towards an unhelpful set of beliefs or actions.
So my main recommendation is for standard cognitive-therapy style self-help, as a place to get started. There need not be any bias in cognitive therapy, since it is merely a neutral frame for your own therapeutic work.
There are others that might aim to help a person develop creativity, or guide one with respect to some other life pursuit, such as building a sense of purpose, meaning, balance, simplicity, etc.
I think it is worthwhile to familiarize yourself with the self-help literature. I think it can be something like getting a textbook for a course at school...while some textbooks may not be very well-written, I think having a textbook at all can at least allow some extra tangible structure in therapeutic work.
Most self-help books have exercises to work through, often requiring you to write things out with pen and paper. I think it is important to actually do the exercises, as opposed to just leafing through the book, or thinking that you've done all those things in your mind before anyway. Working through exercises strengthens the mind, even if the exercises themselves are not very well-constructed. It is something like working through arithmetic or grammar problems. Even if the exercises are boring or trite, the earnest effort spent working through them will strengthen your ability and insight about the subject matter. Also, most self-help books, even if they are poorly written, can act as structures to develop your own personalized insights about the subject matter--the workbooks can be a frame to do the work, as opposed to being an intrinsic source of insight.
Many self-help books are organized with cognitive-behavioural ideas in mind. Once again, even if you don't care much for cognitive therapy, the exercises remain useful, provided you engage in them earnestly (it is possible to do these exercises in a half-hearted or sarcastic way, etc. -- which would minimize any possible benefit, just as with any other exercise in life).
What does evidence have to say about self-help books? So-called "bibliotherapy" (yes, someone had to designate an awkward piece of vocabulary to describe "reading") has an evidence base--here are a few references:
Gregory et al. published this 2006 meta-analysis showing cognitive bibliotherapy was effective for depression: Professional Psychology: Research and Practice 2004, Vol. 35, No. 3, 275–280. They concluded that bibliotherapy had an effect size of about 0.77, which is substantial, and comparable to effect sizes from medications and psychotherapy.
Here is a reference to a 2003 meta-analysis by Newman et al. showing that bibliotherapy was effective in the treatment of various anxiety disorders:
http://www.ncbi.nlm.nih.gov/pubmed/12579544
Here is a 2004 reference showing that guided self-help is effective in treating bulimia:
http://www.ncbi.nlm.nih.gov/pubmed/15101068
In conclusion, I do strongly recommend working through self-help books. I find that it can be important to look at several different ones, as there can be style or content differences causing you to prefer one over the other.
The main word of caution I have about self-help is that some authors may have a very biased point of view (perhaps influenced by dogmatic or eccentric beliefs regarding politics, religion, health care, etc.), and may therefore lead a vulnerable individual towards an unhelpful set of beliefs or actions.
So my main recommendation is for standard cognitive-therapy style self-help, as a place to get started. There need not be any bias in cognitive therapy, since it is merely a neutral frame for your own therapeutic work.
Thursday, January 21, 2010
Rating Scales: limitations & ideas for change
A visitor's comment from one of my previous posts reminded me of an issue I'd thought about before.
In mental health research, symptom scales are often used to measure therapeutic improvement. In depression, the most common scales are the Hamilton Depression Rating Scale (HDRS), the Montgomery-Ashberg Depression Rating Scale (MADRS), or sometimes the Beck Depression Inventory (BDI). The first two examples involve an interviewer assigning a score to a variety of different symptoms or signs. The last example is a scale which is filled out by a patient.
Here are examples of questions from the HDRS, with associated ranges of scoring:
depressed mood (0-4); decreased work & activities (0-4); social withdrawal (0-4); sexual symptoms (0-2); GI symptoms (0-2); weight loss (0-2); weight gain (0-2); appetite increase (0-3); increased eating (0-3); carbohydrate craving (0-3); insomnia (0-6); hypersomnia (0-4); general somatic symptoms (0-2); fatigue (0-4); guilt (0-4); suicidal thoughts/behaviours (0-4); psychological manifestations of anxiety (0-4); somatic manifestations of anxiety (0-4); hypochondriasis (0-4); insight (0-2); motor slowing (0-4); agitation (0-4); diurnal variation (0-2); reverse diurnal variation (0-3); depersonalization (0-4); paranoia (0-3); OCD symptoms (0-2)
One can see from this list that depressive syndromes which have many physical manifestations will obviously score much higher. The highest possible score on the 29-item HDRS is 89. It is likely that physical manifestations of acute depression resolve more quickly, particularly in response to medications. Therefore, the finding that more severe depressions have better response to medication could be simply an artifact of the fact that physical symptoms respond better and more quickly to physical treatments.
A person who is eating and sleeping poorly, is tired, feels and looks physically ill, who is not working, who is not seeing friends as much, and whose symptoms fluctuate in the day, would already get an HDRS score of up to 30 -- without actually feeling depressed or anxious at all! A person feeling very depressed, struggling through life with little pleasure, meaning, satisfaction, or joy -- but sleeping ok, eating ok, and forcing self through daily routines such as work, social relationships, etc. -- might only get a score of 4-6 on this scale.
I acknowledge that the many questions on the HDRS cover a variety of important symptom areas, and improvement in any one of these domains can be very significant.
But -- a big problem of the scale, for me, is that the relative significance of the different symptoms is arbitrarily fixed by the structure of the questionnaire. So, for example, are the 4 points for fatigue of equivalent importance to the 4 points for guilt, or social withdrawal, or depressed mood? Would different individuals rate the relative importance of these symptoms differently? Maybe some people might prefer to sleep better, rather than socialize with greater ease. Also, perhaps some of the symptom questions deserve to be "non-linear," or context-dependent. So, for example, perhaps mild or intermittent depressed mood might deserve a score of only "1". Moderately depressed mood might warrant a score of "5". Severe depressive mood might warrant a score of "20". Or, relentless moderate symptoms over a period of years might warrant a score of "20", while only short-term or episodic moderate symptoms might warrant a score of "5".
It would be interesting to change the weighting of these symptom scores, on an individualized basis.
Also, it would be interesting to see the results of depression treatment studies portrayed with all the separate symptom categories broken down (i.e. to see how the treatment changed each item on the HDRS). Many researchers or statisticians would complain that to portray, or make conclusions, about so many results at once, would reduce the statistical significance. Statistically, a so-called "Bonferroni correction" is necessary if multiple hypotheses are being made simultaneously: if n hypotheses are made, the statistical significance is reduced by a factor of 1/n. Based on this statistical idea, most researchers prefer to analyze just a single quantity, such as the HDRS score, instead of looking at each component of the score separately.
But, this analysis dilutes the data from any study, in the same way that the analysis of artworks in a museum would be diluted if each piece were summarized only by its mass or area.
A more complete analysis would portray every category at once. A graphical presentation would be reasonable, perhaps taking the form of a 3-d surface (once again). The x-axis could represent the different symptom areas (or scores on each item on the HDRS); the y-axis could represent time; and the z-axis could represent the severity. With this analysis, we could say that we are not actually making n hypotheses--we are making a single hypothesis, that the multifactorial pattern of symptom results, manifest as a 3-d surface, is changing over time. Each individual patient's symptom changes, in every symptom category, could be represented on the graph. In this way, no data, or analytic possibility, would be lost or diluted. The reader would be able to inspect every part of the data from the study, and perhaps notice interesting relationships which the original researchers had not considered.
Some patterns of change with different treatment could present in the following ways, as shown in such as 3-d surface:
1) some symptoms improve dramatically with time, while others are much slower to change, or don't change at all. In depression treatment studies, sleep or appetite might change very quickly with a potent antihistaminic drug...this would immediately lead to pronounced improvement on the overall HDRS score, but might not be associated with any significant improvement in mood, energy, concentration, etc.
2) some symptoms might improve immediately, but deteriorate right back to baseline or worse after a few weeks or months. Benzodiazepine treatment would produce such as pattern, in terms of sleep or anxiety improvement. A medication which is sedating but addictive might cause rapid HDRS improvement, but only a careful look at individual category changes over a long period of time would allow us to see the addiction/tolerance pattern. Some people drink alcohol to treat their anxiety symptoms -- such a behaviour might rapidly improve their HDRS scores! But of course, the scores would return to worse than baseline within a few weeks or months. And the person would probably have new symptoms and problems on top of their original ones. So, we must be cautious about getting too excited about claims of rapid HDRS change!
3) some treatments might cause a global change in most or all symptoms...this would be the goal of most treatment strategies. Such a pattern would imply that the multi-symptom syndrome (in this case, the "major depressive disorder" construct) is in fact valid, all components of which improving together with a single treatment.
4) some combined treatments might work well together...for example, a treatment which helps substantially with energy or concentration (such as a stimulant), together with a treatment which helps with mood, socialization, optimism, or anxiety (such as psychotherapy, or an antidepressant). These treatments on their own might appear to be equivalent if only the total HDRS score is considered (since each would reduce symptom points overall); the synergistic effect would only be apparent by looking at each symptom domain separately.
Finally, I think it is important to look at very broad, simple indicators of quality of life, or of general improvement. The "CGI" scale is one example, although it is awkward and imprecise in design, and most likely prone to bias.
Quality of life scales are important as well, in my opinion, since they look at overall satisfaction with life, rather than merely a collection of symptoms.
In practice, only a discussion with the person receiving the treatment can really assess whether it is worthwhile to continue the treatment or not. In such a discussion, the subjective pros and cons of the treatment can be weighed. Even if the treatment has had a minimal impact on a rating score, it might be subjectively beneficial to the person receiving it. And even if the treatment has produced large rating score changes, it might not be the person's preference to continue. I suppose the role of a prescriber is mainly to facilitate such a dialog, and contradict the patient's wishes only if the treatment is objectively causing harm.
In mental health research, symptom scales are often used to measure therapeutic improvement. In depression, the most common scales are the Hamilton Depression Rating Scale (HDRS), the Montgomery-Ashberg Depression Rating Scale (MADRS), or sometimes the Beck Depression Inventory (BDI). The first two examples involve an interviewer assigning a score to a variety of different symptoms or signs. The last example is a scale which is filled out by a patient.
Here are examples of questions from the HDRS, with associated ranges of scoring:
depressed mood (0-4); decreased work & activities (0-4); social withdrawal (0-4); sexual symptoms (0-2); GI symptoms (0-2); weight loss (0-2); weight gain (0-2); appetite increase (0-3); increased eating (0-3); carbohydrate craving (0-3); insomnia (0-6); hypersomnia (0-4); general somatic symptoms (0-2); fatigue (0-4); guilt (0-4); suicidal thoughts/behaviours (0-4); psychological manifestations of anxiety (0-4); somatic manifestations of anxiety (0-4); hypochondriasis (0-4); insight (0-2); motor slowing (0-4); agitation (0-4); diurnal variation (0-2); reverse diurnal variation (0-3); depersonalization (0-4); paranoia (0-3); OCD symptoms (0-2)
One can see from this list that depressive syndromes which have many physical manifestations will obviously score much higher. The highest possible score on the 29-item HDRS is 89. It is likely that physical manifestations of acute depression resolve more quickly, particularly in response to medications. Therefore, the finding that more severe depressions have better response to medication could be simply an artifact of the fact that physical symptoms respond better and more quickly to physical treatments.
A person who is eating and sleeping poorly, is tired, feels and looks physically ill, who is not working, who is not seeing friends as much, and whose symptoms fluctuate in the day, would already get an HDRS score of up to 30 -- without actually feeling depressed or anxious at all! A person feeling very depressed, struggling through life with little pleasure, meaning, satisfaction, or joy -- but sleeping ok, eating ok, and forcing self through daily routines such as work, social relationships, etc. -- might only get a score of 4-6 on this scale.
I acknowledge that the many questions on the HDRS cover a variety of important symptom areas, and improvement in any one of these domains can be very significant.
But -- a big problem of the scale, for me, is that the relative significance of the different symptoms is arbitrarily fixed by the structure of the questionnaire. So, for example, are the 4 points for fatigue of equivalent importance to the 4 points for guilt, or social withdrawal, or depressed mood? Would different individuals rate the relative importance of these symptoms differently? Maybe some people might prefer to sleep better, rather than socialize with greater ease. Also, perhaps some of the symptom questions deserve to be "non-linear," or context-dependent. So, for example, perhaps mild or intermittent depressed mood might deserve a score of only "1". Moderately depressed mood might warrant a score of "5". Severe depressive mood might warrant a score of "20". Or, relentless moderate symptoms over a period of years might warrant a score of "20", while only short-term or episodic moderate symptoms might warrant a score of "5".
It would be interesting to change the weighting of these symptom scores, on an individualized basis.
Also, it would be interesting to see the results of depression treatment studies portrayed with all the separate symptom categories broken down (i.e. to see how the treatment changed each item on the HDRS). Many researchers or statisticians would complain that to portray, or make conclusions, about so many results at once, would reduce the statistical significance. Statistically, a so-called "Bonferroni correction" is necessary if multiple hypotheses are being made simultaneously: if n hypotheses are made, the statistical significance is reduced by a factor of 1/n. Based on this statistical idea, most researchers prefer to analyze just a single quantity, such as the HDRS score, instead of looking at each component of the score separately.
But, this analysis dilutes the data from any study, in the same way that the analysis of artworks in a museum would be diluted if each piece were summarized only by its mass or area.
A more complete analysis would portray every category at once. A graphical presentation would be reasonable, perhaps taking the form of a 3-d surface (once again). The x-axis could represent the different symptom areas (or scores on each item on the HDRS); the y-axis could represent time; and the z-axis could represent the severity. With this analysis, we could say that we are not actually making n hypotheses--we are making a single hypothesis, that the multifactorial pattern of symptom results, manifest as a 3-d surface, is changing over time. Each individual patient's symptom changes, in every symptom category, could be represented on the graph. In this way, no data, or analytic possibility, would be lost or diluted. The reader would be able to inspect every part of the data from the study, and perhaps notice interesting relationships which the original researchers had not considered.
Some patterns of change with different treatment could present in the following ways, as shown in such as 3-d surface:
1) some symptoms improve dramatically with time, while others are much slower to change, or don't change at all. In depression treatment studies, sleep or appetite might change very quickly with a potent antihistaminic drug...this would immediately lead to pronounced improvement on the overall HDRS score, but might not be associated with any significant improvement in mood, energy, concentration, etc.
2) some symptoms might improve immediately, but deteriorate right back to baseline or worse after a few weeks or months. Benzodiazepine treatment would produce such as pattern, in terms of sleep or anxiety improvement. A medication which is sedating but addictive might cause rapid HDRS improvement, but only a careful look at individual category changes over a long period of time would allow us to see the addiction/tolerance pattern. Some people drink alcohol to treat their anxiety symptoms -- such a behaviour might rapidly improve their HDRS scores! But of course, the scores would return to worse than baseline within a few weeks or months. And the person would probably have new symptoms and problems on top of their original ones. So, we must be cautious about getting too excited about claims of rapid HDRS change!
3) some treatments might cause a global change in most or all symptoms...this would be the goal of most treatment strategies. Such a pattern would imply that the multi-symptom syndrome (in this case, the "major depressive disorder" construct) is in fact valid, all components of which improving together with a single treatment.
4) some combined treatments might work well together...for example, a treatment which helps substantially with energy or concentration (such as a stimulant), together with a treatment which helps with mood, socialization, optimism, or anxiety (such as psychotherapy, or an antidepressant). These treatments on their own might appear to be equivalent if only the total HDRS score is considered (since each would reduce symptom points overall); the synergistic effect would only be apparent by looking at each symptom domain separately.
Finally, I think it is important to look at very broad, simple indicators of quality of life, or of general improvement. The "CGI" scale is one example, although it is awkward and imprecise in design, and most likely prone to bias.
Quality of life scales are important as well, in my opinion, since they look at overall satisfaction with life, rather than merely a collection of symptoms.
In practice, only a discussion with the person receiving the treatment can really assess whether it is worthwhile to continue the treatment or not. In such a discussion, the subjective pros and cons of the treatment can be weighed. Even if the treatment has had a minimal impact on a rating score, it might be subjectively beneficial to the person receiving it. And even if the treatment has produced large rating score changes, it might not be the person's preference to continue. I suppose the role of a prescriber is mainly to facilitate such a dialog, and contradict the patient's wishes only if the treatment is objectively causing harm.
Wednesday, January 13, 2010
Antidepressants only effective in severest depression?
A recent article in JAMA by Fournier et al. is a meta-analysis of antidepressant treatment effects assessed in relation to depression severity. Here's the reference:
http://www.ncbi.nlm.nih.gov/pubmed/20051569
The results show that antidepressants work significantly well, compared to placebo, only for very severe depression (corresponding to Hamilton Depression Rating Scale scores of at least 25).
The analysis is quite well-done, and the results are also presented in a graphical form clearly showing a linear increase in antidepressant effect as baseline depression scores increase.
The authors observe that antidepressants are most commonly prescribed to people who have milder depressions--a population in which they show that medications arguably do not work.
Here are a few of my criticisms of this study:
1) the duration of each trial included in the meta-analysis was between 6 and 11 weeks. In my opinion, depressive disorders are long-term, highly recurrent problems, which have a natural period over at least 6-11 months, not 6-11 weeks. Treatments to address mood disorders of any severity require much longer durations. The short duration could cause a significant under-estimation of treatment effects.
2) the study, like many, looks at "depression alone." In most real-life situations, outside of a research study, individuals have several different problems, such as mild depression + social anxiety, or mild depression + panic attacks, etc. The presence of other symptoms, particularly anxiety symptoms, most likely would increase the likelihood of antidepressants helping.
3) Milder depressions, just like more severe depressions, may actually improve more consistently with a "second step" such as combination with psychotherapy, or combining two different antidepressants. The mildness of a medical syndrome does not necessarily mean that the effective treatments need only to be "mild."
4) Milder depressive syndromes may be more prone to misdiagnosis.
5) current "resolution" to measure treatment effects in depression is quite poor. "Depression" is a very broad category. An analogy could be considering "abdominal pain" to be a diagnostic category. If "abdominal pain" is the only category, and is simply rated on a severity scale (rather than subcategorized to obtain a precise diagnosis), and the treatment offered for "abdominal pain" is appendectomy, then we would probably see no difference in treatment effectiveness between appendectomy and placebo. This is because appendectomy is only effective to treat appendicitis (a subset of the abdominal pain population), and is either ineffective or harmful in treating abdominal pain patients without appendicitis (except, perhaps, for those patients who have a placebo improvement of psychosomatic or factitious abdominal pain, an improvement which they attribute to having surgery).
We currently do not have the science to subcategorize depression in a more clinically meaningful way (there are subcategorization schemes, but they don't have much relevance in terms of treatment).
But we do have a research method which could improve "resolution":
-instead of comparing two populations of depressed individuals, one group receiving antidepressant (or some other treatment), and the other receiving placebo (or some other alternative), the study design could instead be to offer every individual courses of placebo, alternating with antidepressant (or "treatment one" alternating with "treatment two"). Each course of treatment would have to last an adequate length of time. The analysis would aim to show whether there is a subset of individuals who respond to the antidepressant, or a subset of individuals who do better with placebo. The averaged results over the whole group might show that antidepressant effects do not differ from placebo (just like appendectomy might not differ from placebo in treating "abdominal pain"), but the individualized result could show that some individuals improve substantially with the antidepressant (just like appendectomy would save the lives of the small group of "abdominal pain" patients who have appendicitis).
---
In the meantime, though, I think it is reasonable to recognize that antidepressants are less consistently helpful when symptoms are less severe.
http://www.ncbi.nlm.nih.gov/pubmed/20051569
The results show that antidepressants work significantly well, compared to placebo, only for very severe depression (corresponding to Hamilton Depression Rating Scale scores of at least 25).
The analysis is quite well-done, and the results are also presented in a graphical form clearly showing a linear increase in antidepressant effect as baseline depression scores increase.
The authors observe that antidepressants are most commonly prescribed to people who have milder depressions--a population in which they show that medications arguably do not work.
Here are a few of my criticisms of this study:
1) the duration of each trial included in the meta-analysis was between 6 and 11 weeks. In my opinion, depressive disorders are long-term, highly recurrent problems, which have a natural period over at least 6-11 months, not 6-11 weeks. Treatments to address mood disorders of any severity require much longer durations. The short duration could cause a significant under-estimation of treatment effects.
2) the study, like many, looks at "depression alone." In most real-life situations, outside of a research study, individuals have several different problems, such as mild depression + social anxiety, or mild depression + panic attacks, etc. The presence of other symptoms, particularly anxiety symptoms, most likely would increase the likelihood of antidepressants helping.
3) Milder depressions, just like more severe depressions, may actually improve more consistently with a "second step" such as combination with psychotherapy, or combining two different antidepressants. The mildness of a medical syndrome does not necessarily mean that the effective treatments need only to be "mild."
4) Milder depressive syndromes may be more prone to misdiagnosis.
5) current "resolution" to measure treatment effects in depression is quite poor. "Depression" is a very broad category. An analogy could be considering "abdominal pain" to be a diagnostic category. If "abdominal pain" is the only category, and is simply rated on a severity scale (rather than subcategorized to obtain a precise diagnosis), and the treatment offered for "abdominal pain" is appendectomy, then we would probably see no difference in treatment effectiveness between appendectomy and placebo. This is because appendectomy is only effective to treat appendicitis (a subset of the abdominal pain population), and is either ineffective or harmful in treating abdominal pain patients without appendicitis (except, perhaps, for those patients who have a placebo improvement of psychosomatic or factitious abdominal pain, an improvement which they attribute to having surgery).
We currently do not have the science to subcategorize depression in a more clinically meaningful way (there are subcategorization schemes, but they don't have much relevance in terms of treatment).
But we do have a research method which could improve "resolution":
-instead of comparing two populations of depressed individuals, one group receiving antidepressant (or some other treatment), and the other receiving placebo (or some other alternative), the study design could instead be to offer every individual courses of placebo, alternating with antidepressant (or "treatment one" alternating with "treatment two"). Each course of treatment would have to last an adequate length of time. The analysis would aim to show whether there is a subset of individuals who respond to the antidepressant, or a subset of individuals who do better with placebo. The averaged results over the whole group might show that antidepressant effects do not differ from placebo (just like appendectomy might not differ from placebo in treating "abdominal pain"), but the individualized result could show that some individuals improve substantially with the antidepressant (just like appendectomy would save the lives of the small group of "abdominal pain" patients who have appendicitis).
---
In the meantime, though, I think it is reasonable to recognize that antidepressants are less consistently helpful when symptoms are less severe.
Thursday, November 19, 2009
Physical Warmth promotes Interpersonal Warmth
In an amusing study by LE Williams and JA Bargh, published in Science in 2008, subjects exposed to warm objects behaved in a manner which was more interpersonally warm. Here is the reference:
http://www.ncbi.nlm.nih.gov/pubmed/18948544
In the first experiment described by the authors, subjects in the elevator on the way to the study lab were asked to hold an experimenter's drink cup for a moment, while the experimenter wrote some identifying information down on a clipboard. The experimenter in the elevator did not have knowledge of the study's hypotheses. In the study lab afterward, the subjects were given a brief written description of a person (the same description given to all subjects), and were asked to rate that person in terms of a variety of personality dimensions. The subjects who briefly had held a cup of hot coffee gave personality ratings that were significantly "warmer," compared to the subjects who had held a cup of iced coffee. The ratings for warmth were 4.71 out of 7 for the "hot coffee" group, compared to 4.25 out of 7 for the "iced coffee" group; these differed with a p value of 0.05. "Warmth" in this sense refers to traits such as friendliness, helpfulness, and trustworthiness.
The second experiment was more blinded, in that the experimenters did not know whether the subjects were handling a warm or cold object. This time, subjects were offered a choice of two types of gifts after the experiment: the first type would be for personal use, the second would be a gift for a friend. Those who had handled a warm object were substantially more likely to choose a gift for a friend, rather than for themselves.
Those who had handled a cold object chose a "selfish" gift 75% of the time.
Those who had handled a warm object chose the "selfish" gift 46% of the time.
The authors discuss attachment theory, and suggest that one explanation for these findings, on a neurobiological level, is that the insular cortex in the brain is responsible for processing information about both physical and psychological warmth, therefore the two types of warmth perception may influence each other.
I find this type of cross-sectional social-psychological research fun and a bit lighthearted, but often containing kernels of wisdom.
It would be interesting to do similar studies of this sort, but with different groups of subjects who are stratified according to interpersonal style, depressive symptoms, etc. Perhaps there are subjects who are most sensitive to these environmental effects.
I'm amused and delighted, in any case, that figurative or "metaphorical" warmth seems to match up with literal or physical warmth. A nice meeting of the metaphorical with the literal. Perhaps this is typical of what the brain does.
In any case, this little piece of evidence further supports the recommendation to do sensually pleasing, "warmth-oriented" activities, as part of a regimen for maintaining psychosocial health. There may be something in particular about heat which could be therapeutic. Hot baths are anecdotally helpful for relaxation, pain relief, and to promote deeper sleep. I've encountered a few examples in which people found saunas quite helpful for seasonal depressive symptoms. Maybe a very warm, cozy sweater can be helpful for your mental health, and even have positive effects on others!
Here are references to a few studies showing improvement in insomnia following hot baths:
http://www.ncbi.nlm.nih.gov/pubmed/10566907 {a 1999 study from the journal Sleep, showing improvements in sleep continuity and more slow-wave sleep earlier in the night, in older females with insomnia who had 40-40.5 °C baths 1.5-2 hours before bedtime}
http://www.ncbi.nlm.nih.gov/pubmed/15879585 {a 2005 study in the American Journal of Geriatric Psychiatry showing improved sleep in elderly people with vascular dementia, following 30 minute baths in 40°C water, 2 hours before bedtime}
A precipitant of some seasonal depression, at least in Canada, may be not only the darkness but the cold. The cold may lead not only to a disinclination to go outside, but also to a less generous or a "colder" interpersonal stance, which would further perpetuate a depressive cycle. This is another reason to heed that advice mothers often give young children, to dress warmly in the winter.
Here is a link to the abstract of a study from Japan, published in Psychosomatic Medicine in 2005: http://www.ncbi.nlm.nih.gov/pubmed/16046381
In this study, mildly depressed subjects were randomized to receive one of two treatments, 5 days per week, for 4 weeks, in addition to daily physical and occupational therapy:
1) "thermal therapy" in a 60 °C sauna for 15 minutes, followed by 30 minutes wrapped in a blanket, in a 28 °C room.
2) "non-thermal therapy" of 45 minutes in a 24°C room
The thermal therapy group had a 33% reduction in psychological symptoms, compared to a 14% reduction in the non-thermal therapy group.
The thermal group had a 42% reduction in somatic complaints, compared to an 8% reduction in the non-thermal group.
The research literature on this subject is quite limited, but there is some evidence that warmth--physical and psychological--is therapeutic!
http://www.ncbi.nlm.nih.gov/pubmed/18948544
In the first experiment described by the authors, subjects in the elevator on the way to the study lab were asked to hold an experimenter's drink cup for a moment, while the experimenter wrote some identifying information down on a clipboard. The experimenter in the elevator did not have knowledge of the study's hypotheses. In the study lab afterward, the subjects were given a brief written description of a person (the same description given to all subjects), and were asked to rate that person in terms of a variety of personality dimensions. The subjects who briefly had held a cup of hot coffee gave personality ratings that were significantly "warmer," compared to the subjects who had held a cup of iced coffee. The ratings for warmth were 4.71 out of 7 for the "hot coffee" group, compared to 4.25 out of 7 for the "iced coffee" group; these differed with a p value of 0.05. "Warmth" in this sense refers to traits such as friendliness, helpfulness, and trustworthiness.
The second experiment was more blinded, in that the experimenters did not know whether the subjects were handling a warm or cold object. This time, subjects were offered a choice of two types of gifts after the experiment: the first type would be for personal use, the second would be a gift for a friend. Those who had handled a warm object were substantially more likely to choose a gift for a friend, rather than for themselves.
Those who had handled a cold object chose a "selfish" gift 75% of the time.
Those who had handled a warm object chose the "selfish" gift 46% of the time.
The authors discuss attachment theory, and suggest that one explanation for these findings, on a neurobiological level, is that the insular cortex in the brain is responsible for processing information about both physical and psychological warmth, therefore the two types of warmth perception may influence each other.
I find this type of cross-sectional social-psychological research fun and a bit lighthearted, but often containing kernels of wisdom.
It would be interesting to do similar studies of this sort, but with different groups of subjects who are stratified according to interpersonal style, depressive symptoms, etc. Perhaps there are subjects who are most sensitive to these environmental effects.
I'm amused and delighted, in any case, that figurative or "metaphorical" warmth seems to match up with literal or physical warmth. A nice meeting of the metaphorical with the literal. Perhaps this is typical of what the brain does.
In any case, this little piece of evidence further supports the recommendation to do sensually pleasing, "warmth-oriented" activities, as part of a regimen for maintaining psychosocial health. There may be something in particular about heat which could be therapeutic. Hot baths are anecdotally helpful for relaxation, pain relief, and to promote deeper sleep. I've encountered a few examples in which people found saunas quite helpful for seasonal depressive symptoms. Maybe a very warm, cozy sweater can be helpful for your mental health, and even have positive effects on others!
Here are references to a few studies showing improvement in insomnia following hot baths:
http://www.ncbi.nlm.nih.gov/pubmed/10566907 {a 1999 study from the journal Sleep, showing improvements in sleep continuity and more slow-wave sleep earlier in the night, in older females with insomnia who had 40-40.5 °C baths 1.5-2 hours before bedtime}
http://www.ncbi.nlm.nih.gov/pubmed/15879585 {a 2005 study in the American Journal of Geriatric Psychiatry showing improved sleep in elderly people with vascular dementia, following 30 minute baths in 40°C water, 2 hours before bedtime}
A precipitant of some seasonal depression, at least in Canada, may be not only the darkness but the cold. The cold may lead not only to a disinclination to go outside, but also to a less generous or a "colder" interpersonal stance, which would further perpetuate a depressive cycle. This is another reason to heed that advice mothers often give young children, to dress warmly in the winter.
Here is a link to the abstract of a study from Japan, published in Psychosomatic Medicine in 2005: http://www.ncbi.nlm.nih.gov/pubmed/16046381
In this study, mildly depressed subjects were randomized to receive one of two treatments, 5 days per week, for 4 weeks, in addition to daily physical and occupational therapy:
1) "thermal therapy" in a 60 °C sauna for 15 minutes, followed by 30 minutes wrapped in a blanket, in a 28 °C room.
2) "non-thermal therapy" of 45 minutes in a 24°C room
The thermal therapy group had a 33% reduction in psychological symptoms, compared to a 14% reduction in the non-thermal therapy group.
The thermal group had a 42% reduction in somatic complaints, compared to an 8% reduction in the non-thermal group.
The research literature on this subject is quite limited, but there is some evidence that warmth--physical and psychological--is therapeutic!
Thursday, November 5, 2009
More evidence about the impact of nutrition on mood
An important paper was just published by Akbaraly et al. in The British Journal of Psychiatry, in which 3486 people were followed prospectively for 5 years, with an analysis of nutritional habits and depression symptoms. Here's a link to the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/19880930
The data showed that individuals consuming a diet rich in "processed foods" (such as sweetened desserts, fried food, processed meat, refined grains, and high-fat dairy products) had a much higher rate of depression compared to those consuming a diet heavily loaded with vegetables, fruits, and fish.
The analysis controlled for confounding factors such as gender, age, caloric intake, marital status, employment grade, education, smoking, physical activity, hypertension, diabetes, and cardiovascular disease. A component of the analysis also strongly suggests that the association is not due to reverse causation, of depression leading to worse nutrition. Rather, the analysis strongly suggests that poor diet is a component of causation: that is, poor diet directly increases the risk of becoming depressed, or of having worse depressive symptoms.
Those in the third of people with diets highest in processed foods had a 58% higher chance of having clinical depression compared to the third of people with the healthiest diets.
So, once again, more evidence-based advice to eat healthily in order to protect your mental health:
-more vegetables, fruits, and fish
-less sweets, fried foods, white flour, whole milk, ice cream, etc.
http://www.ncbi.nlm.nih.gov/pubmed/19880930
The data showed that individuals consuming a diet rich in "processed foods" (such as sweetened desserts, fried food, processed meat, refined grains, and high-fat dairy products) had a much higher rate of depression compared to those consuming a diet heavily loaded with vegetables, fruits, and fish.
The analysis controlled for confounding factors such as gender, age, caloric intake, marital status, employment grade, education, smoking, physical activity, hypertension, diabetes, and cardiovascular disease. A component of the analysis also strongly suggests that the association is not due to reverse causation, of depression leading to worse nutrition. Rather, the analysis strongly suggests that poor diet is a component of causation: that is, poor diet directly increases the risk of becoming depressed, or of having worse depressive symptoms.
Those in the third of people with diets highest in processed foods had a 58% higher chance of having clinical depression compared to the third of people with the healthiest diets.
So, once again, more evidence-based advice to eat healthily in order to protect your mental health:
-more vegetables, fruits, and fish
-less sweets, fried foods, white flour, whole milk, ice cream, etc.
Thursday, October 29, 2009
Spread of psychological phenomena in social networks
Here is a link to the abstract of an interesting article by Fowler & Christakis, published in the British Medical Journal in December 2008:
http://www.ncbi.nlm.nih.gov/pubmed/19056788
I think it is a delightful statistical analysis of social networks, based on a cohort of about 5000 people from the Framingham Heart Study, followed over 20 years. This article should really be read in its entirety, in order to appreciate the sophistication of the techniques.
They showed that happiness "spreads" in a manner analogous to contagion. Having happy same-sex friends or neighbours who live nearby, increases one's likelihood of being, or becoming, happy. Interestingly, spouses and coworkers did not have a pronounced effect.
Also, the findings show that having "unhappy" friends does not cause a similar increase in likelihood of being or becoming "unhappy" -- it is happiness, not unhappiness, in the social network, which appears to "spread."
So the message here is not that people should avoid unhappy friends: in fact the message can be that befriending an unhappy person can be helpful not only to that unhappy individual, but to that unhappy person's social network.
There has been some criticism of the authors' techniques, but overall I find the analysis to be very thorough, imaginative, and fascinating.
Here are some practical applications suggested by these findings:
1) sharing positive emotions can have a substantial positive, lasting emotional impact on people near you, including friends and neighbours.
2) nurturing friendships with happier people who live close to you may help to improve subjective happiness
3) this does not mean that friendships with unhappy people have a negative emotional impact, unless all of your friendships are with unhappy people.
4) in the treatment of depression, consideration of the health of social networks can be very important. Here, the "quantity" of the extended social network is not relevant (so the number of "facebook friends" doesn't matter). Rather, the relevant effects are due to the characteristics of the close social network, of 2-6 people or so, particularly those who have close geographic proximity. As I look at the data, I see that having two "happy friends" has a significantly larger positive effect than having only one, but there was not much further effect from having more than two.
5) I have to wonder whether the value of group therapy for depression is diminished if all members of the group are severely depressed. I could see group therapy being much more effective if some of the members were in a recovered, or recovering, state. This reminds me of some of the research about social learning theory (see my previous post: http://garthkroeker.blogspot.com/2008/12/social-learning-therapy.html)
6) on a public health level, the expense involved in treating individual cases of depression should be considered not only on the basis of considering that individual's improved health, function, and well-being, but also on the basis of considering that individual's positive health impact on his or her social network.
7) There is individual variability in social extroversion, or social need. Some individuals prefer a very active social life, others prefer relative social isolation. Others desire social activity, but are isolated or socially anxious. Those who live in relative social isolation might still have a positive reciprocal experience of this social network effect, provided that relationships with people living nearby (such as next-door neighbours or family) are positive.
I should conclude that, despite the strength of the authors' analysis, involving a very large epidemiological cohort, my inferences and proposed applications mentioned above could only really be proven definitively through randomized prospective studies. Yet, such studies would be virtually impossible to do! I think some of the social psychology literature attempts to address this, but I think manages to do so only in a more limited and cross-sectional manner.
http://www.ncbi.nlm.nih.gov/pubmed/19056788
I think it is a delightful statistical analysis of social networks, based on a cohort of about 5000 people from the Framingham Heart Study, followed over 20 years. This article should really be read in its entirety, in order to appreciate the sophistication of the techniques.
They showed that happiness "spreads" in a manner analogous to contagion. Having happy same-sex friends or neighbours who live nearby, increases one's likelihood of being, or becoming, happy. Interestingly, spouses and coworkers did not have a pronounced effect.
Also, the findings show that having "unhappy" friends does not cause a similar increase in likelihood of being or becoming "unhappy" -- it is happiness, not unhappiness, in the social network, which appears to "spread."
So the message here is not that people should avoid unhappy friends: in fact the message can be that befriending an unhappy person can be helpful not only to that unhappy individual, but to that unhappy person's social network.
There has been some criticism of the authors' techniques, but overall I find the analysis to be very thorough, imaginative, and fascinating.
Here are some practical applications suggested by these findings:
1) sharing positive emotions can have a substantial positive, lasting emotional impact on people near you, including friends and neighbours.
2) nurturing friendships with happier people who live close to you may help to improve subjective happiness
3) this does not mean that friendships with unhappy people have a negative emotional impact, unless all of your friendships are with unhappy people.
4) in the treatment of depression, consideration of the health of social networks can be very important. Here, the "quantity" of the extended social network is not relevant (so the number of "facebook friends" doesn't matter). Rather, the relevant effects are due to the characteristics of the close social network, of 2-6 people or so, particularly those who have close geographic proximity. As I look at the data, I see that having two "happy friends" has a significantly larger positive effect than having only one, but there was not much further effect from having more than two.
5) I have to wonder whether the value of group therapy for depression is diminished if all members of the group are severely depressed. I could see group therapy being much more effective if some of the members were in a recovered, or recovering, state. This reminds me of some of the research about social learning theory (see my previous post: http://garthkroeker.blogspot.com/2008/12/social-learning-therapy.html)
6) on a public health level, the expense involved in treating individual cases of depression should be considered not only on the basis of considering that individual's improved health, function, and well-being, but also on the basis of considering that individual's positive health impact on his or her social network.
7) There is individual variability in social extroversion, or social need. Some individuals prefer a very active social life, others prefer relative social isolation. Others desire social activity, but are isolated or socially anxious. Those who live in relative social isolation might still have a positive reciprocal experience of this social network effect, provided that relationships with people living nearby (such as next-door neighbours or family) are positive.
I should conclude that, despite the strength of the authors' analysis, involving a very large epidemiological cohort, my inferences and proposed applications mentioned above could only really be proven definitively through randomized prospective studies. Yet, such studies would be virtually impossible to do! I think some of the social psychology literature attempts to address this, but I think manages to do so only in a more limited and cross-sectional manner.
Tuesday, October 20, 2009
"Positive Psychotherapy" (PPT) for depression
This post is a continuation of my earlier post on the psychology of happiness. I'm trying to look at each of the references in more detail.
PPT (positive psychotherapy) is a technique described in a paper by Seligman et al. Here's a reference, from American Psychologist in 2006:
http://www.ncbi.nlm.nih.gov/pubmed/17115810
In this paper the technique was tested on two groups. The more important finding concerns the application of PPT with severely depressed adults. PPT was compared with "treatment as usual" (mainly supportive therapy), and "treatment as usual plus antidepressant". The trial lasted 12 weeks, and there was follow-up over 1 year.
The PPT group showed significant improvement in depression scores, and significantly increased happiness, compared to the two control groups.
More controlled studies need to be done on the technique, but in the meantime, the ideas are simple, valuable, potentially enjoyable, and easily incorporated into other therapy styles such as CBT. Here are some of the exercises recommended in PPT, as described in the paper mentioned above:
1) Write a 300-word positive autobiographical introduction, which includes a concrete story illustrating character strengths
2) Identify "signature strengths" based on exercise (1), and discuss situations in which these have helped. Consider ways to use these strengths more in daily life
3) Write a journal describing 3 good things (large or small) that happen each day
4) Describe 3 bad memories, associated anger, and their impact on maintaining depression (this exercise to be done just once or a few times, not every day)
5) Write a letter of forgiveness describing a transgression from the past, with a pledge to forgive (the letter need not be actually sent)
6) Write a letter of gratitude to someone who was never properly thanked
7) Avoiding an attitude of "maximizing" as a goal, rather focusing on meaningfully engaging with what is enough (i.e. avoiding addictive hedonism, in terms of materialism or achievement). The authors use the term "satisficing", which led me to look this word up--here's a good article I found: http://en.wikipedia.org/wiki/Satisficing). I think this idea is really important for those of us who are very perfectionistic or who have very specific, fixed standards for the way they believe life should be, and who therefore feel that real life is always lagging behind these expectations or requirements, or that real life could at any moment crash into a state of failure.
8) Identification of 3 negative life events ("doors closed") which led to 3 positives ("doors opened").
9) Identification of the "signature strengths" of a significant other.
10) Give enthusiastic positive feedback to positive events reported by others, at least once per day
11) Arrange a date to celebrate the strengths of oneself and of a significant other
12) Analyze "signature strengths" among family members
13) Plan and engage with a "savoring" activity, in which something pleasurable is done, with conscious attention given to how pleasurable it is, and with plenty of time reserved to do it
14) "Giving a gift of time" by contributing to another person, or to the community, a substantial amount of time, using one of your signature strengths. This could include volunteering.
Here's a link to a blog devoted to positive psychology techniques:
http://blog.happier.com/
This blog is connected to a site in which they want you to sign up and pay for a membership. I'm always a bit jarred when an altruistic psychotherapeutic system is marketed for financial profit. Would it not be more satisfying to everyone to offer this for free? Also I think the photograph of an ecstatic woman in a flowery meadow is a bit over-the-top as advertising for the site. I find the marketing excessively aggressive, it looks like an infomercial. Some of this stuff could really be off-putting to weary, understandably cynical individuals with chronic depression who have tried many other types of therapy already. And there can be a sort of religious fervor among enthusiastic adherents of a new technique, which can skew reason.
Yet, these ideas are worth looking at. And I certainly agree that in psychiatry, and in therapy, we often focus excessively on the negative side of things, and do not attend enough to nurturing the positive.
PPT (positive psychotherapy) is a technique described in a paper by Seligman et al. Here's a reference, from American Psychologist in 2006:
http://www.ncbi.nlm.nih.gov/pubmed/17115810
In this paper the technique was tested on two groups. The more important finding concerns the application of PPT with severely depressed adults. PPT was compared with "treatment as usual" (mainly supportive therapy), and "treatment as usual plus antidepressant". The trial lasted 12 weeks, and there was follow-up over 1 year.
The PPT group showed significant improvement in depression scores, and significantly increased happiness, compared to the two control groups.
More controlled studies need to be done on the technique, but in the meantime, the ideas are simple, valuable, potentially enjoyable, and easily incorporated into other therapy styles such as CBT. Here are some of the exercises recommended in PPT, as described in the paper mentioned above:
1) Write a 300-word positive autobiographical introduction, which includes a concrete story illustrating character strengths
2) Identify "signature strengths" based on exercise (1), and discuss situations in which these have helped. Consider ways to use these strengths more in daily life
3) Write a journal describing 3 good things (large or small) that happen each day
4) Describe 3 bad memories, associated anger, and their impact on maintaining depression (this exercise to be done just once or a few times, not every day)
5) Write a letter of forgiveness describing a transgression from the past, with a pledge to forgive (the letter need not be actually sent)
6) Write a letter of gratitude to someone who was never properly thanked
7) Avoiding an attitude of "maximizing" as a goal, rather focusing on meaningfully engaging with what is enough (i.e. avoiding addictive hedonism, in terms of materialism or achievement). The authors use the term "satisficing", which led me to look this word up--here's a good article I found: http://en.wikipedia.org/wiki/Satisficing). I think this idea is really important for those of us who are very perfectionistic or who have very specific, fixed standards for the way they believe life should be, and who therefore feel that real life is always lagging behind these expectations or requirements, or that real life could at any moment crash into a state of failure.
8) Identification of 3 negative life events ("doors closed") which led to 3 positives ("doors opened").
9) Identification of the "signature strengths" of a significant other.
10) Give enthusiastic positive feedback to positive events reported by others, at least once per day
11) Arrange a date to celebrate the strengths of oneself and of a significant other
12) Analyze "signature strengths" among family members
13) Plan and engage with a "savoring" activity, in which something pleasurable is done, with conscious attention given to how pleasurable it is, and with plenty of time reserved to do it
14) "Giving a gift of time" by contributing to another person, or to the community, a substantial amount of time, using one of your signature strengths. This could include volunteering.
Here's a link to a blog devoted to positive psychology techniques:
http://blog.happier.com/
This blog is connected to a site in which they want you to sign up and pay for a membership. I'm always a bit jarred when an altruistic psychotherapeutic system is marketed for financial profit. Would it not be more satisfying to everyone to offer this for free? Also I think the photograph of an ecstatic woman in a flowery meadow is a bit over-the-top as advertising for the site. I find the marketing excessively aggressive, it looks like an infomercial. Some of this stuff could really be off-putting to weary, understandably cynical individuals with chronic depression who have tried many other types of therapy already. And there can be a sort of religious fervor among enthusiastic adherents of a new technique, which can skew reason.
Yet, these ideas are worth looking at. And I certainly agree that in psychiatry, and in therapy, we often focus excessively on the negative side of things, and do not attend enough to nurturing the positive.
Mindfulness actually works
So-called "mindfulness" techniques have been recommended in the treatment of a variety of problems, including chronic physical pain, emotional lability, anxiety, borderline personality symptoms, etc.
I do not think mindfulness training is a complete answer to any of these complex problems, but it could be an extremely valuable, essential component in therapy and growth.
I think now of a metaphor of a growing seedling, or a baby bird: these creatures require stable environments in order to grow. Internal and external environments may not always be stable, though. This instability may be caused by many internal and external biological, environmental, social, or psychological factors. In an unstable environment, growth cannot occur--it gets disrupted, uprooted, or drowned, over and over again, by painful waves of symptoms. Mindfulness techniques can be a way to deal with this type of pain, by taking away from the pain its power to disrupt, uproot, or drown. In itself it may not lead to psychological health, but it may permit a stable ground on which to start growing and building health.
Mindfulness on its own may not always stop pain, but it may lay the groundwork for an environment in which the causes of the pain may finally be dealt with and relieved. In this way mindfulness can be more a catalyst for change than a force of change.
Here is some research evidence:
http://www.ncbi.nlm.nih.gov/pubmed/1609875
http://www.ncbi.nlm.nih.gov/pubmed/7649463
This is a link to two of Kabat-Zinn's papers: the first describes the results of an 8-week mindfulness meditation course on anxiety symptoms in a cohort of 22 patients, and the second describes a 3-year follow-up on these same patients. The results show persistent, substantial reductions in all anxiety symptoms. The studies are weakened by the lack of placebo groups and randomization. But the initial cohort had quite chronic and severe anxiety symptoms (of average duration 6.8 years). Symptom scores declined by about 50%, which is very significant for chronic anxiety disorder patients, and represent a radical improvement in quality of life.
These papers suggest that mindfulness does not merely "increase acceptance of pain"--they suggest that mindfulness also leads to direct reduction of symptoms.
http://www.ncbi.nlm.nih.gov/pubmed/3897551
This is a link to one of Kabat-Zinn's original papers showing substantial symptom improvement and quality-of-life improvement in 90 chronic pain patients who did a 10-week mindfulness meditation course.
http://www.ncbi.nlm.nih.gov/pubmed/15256293
This is a 2004 meta-analysis concluding that mindfulness training, for a variety of different syndromes of emotional or physical pain, has an average effect size of about 0.5, which strongly suggests a very significant clinical benefit. It does come from a potentially biased source, "the Freiburg Institute for Mindfulness Research." But the study itself appears to be well put-together.
http://www.ncbi.nlm.nih.gov/pubmed/17544212
This randomized, controlled 8 week study showed slight improvements in various symptoms among elderly subjects with chronic low back pain. Pain scores (i.e. quantified measures of subjective pain) did not actually change significantly. And quality of life scores didn't change very much either. So I think the results of this study should not be overstated.
I do think that 8 weeks is too short. Also the degree of "immersion" for a technique like this is likely to be an extremely important factor. I think 8 weeks of 6 hours per day would be much more effective. Or a 1-year study of 1-hour per day. Techniques such as meditation are similar to learning languages or musical skills, and these types of abilities require much more lengthy, immersive practice in order to develop.
In the meantime, I encourage people to inform themselves about mindfulness techniques, and consider reserving some time to develop mindfulness skills.
I do not think mindfulness training is a complete answer to any of these complex problems, but it could be an extremely valuable, essential component in therapy and growth.
I think now of a metaphor of a growing seedling, or a baby bird: these creatures require stable environments in order to grow. Internal and external environments may not always be stable, though. This instability may be caused by many internal and external biological, environmental, social, or psychological factors. In an unstable environment, growth cannot occur--it gets disrupted, uprooted, or drowned, over and over again, by painful waves of symptoms. Mindfulness techniques can be a way to deal with this type of pain, by taking away from the pain its power to disrupt, uproot, or drown. In itself it may not lead to psychological health, but it may permit a stable ground on which to start growing and building health.
Mindfulness on its own may not always stop pain, but it may lay the groundwork for an environment in which the causes of the pain may finally be dealt with and relieved. In this way mindfulness can be more a catalyst for change than a force of change.
Here is some research evidence:
http://www.ncbi.nlm.nih.gov/pubmed/1609875
http://www.ncbi.nlm.nih.gov/pubmed/7649463
This is a link to two of Kabat-Zinn's papers: the first describes the results of an 8-week mindfulness meditation course on anxiety symptoms in a cohort of 22 patients, and the second describes a 3-year follow-up on these same patients. The results show persistent, substantial reductions in all anxiety symptoms. The studies are weakened by the lack of placebo groups and randomization. But the initial cohort had quite chronic and severe anxiety symptoms (of average duration 6.8 years). Symptom scores declined by about 50%, which is very significant for chronic anxiety disorder patients, and represent a radical improvement in quality of life.
These papers suggest that mindfulness does not merely "increase acceptance of pain"--they suggest that mindfulness also leads to direct reduction of symptoms.
http://www.ncbi.nlm.nih.gov/pubmed/3897551
This is a link to one of Kabat-Zinn's original papers showing substantial symptom improvement and quality-of-life improvement in 90 chronic pain patients who did a 10-week mindfulness meditation course.
http://www.ncbi.nlm.nih.gov/pubmed/15256293
This is a 2004 meta-analysis concluding that mindfulness training, for a variety of different syndromes of emotional or physical pain, has an average effect size of about 0.5, which strongly suggests a very significant clinical benefit. It does come from a potentially biased source, "the Freiburg Institute for Mindfulness Research." But the study itself appears to be well put-together.
http://www.ncbi.nlm.nih.gov/pubmed/17544212
This randomized, controlled 8 week study showed slight improvements in various symptoms among elderly subjects with chronic low back pain. Pain scores (i.e. quantified measures of subjective pain) did not actually change significantly. And quality of life scores didn't change very much either. So I think the results of this study should not be overstated.
I do think that 8 weeks is too short. Also the degree of "immersion" for a technique like this is likely to be an extremely important factor. I think 8 weeks of 6 hours per day would be much more effective. Or a 1-year study of 1-hour per day. Techniques such as meditation are similar to learning languages or musical skills, and these types of abilities require much more lengthy, immersive practice in order to develop.
In the meantime, I encourage people to inform themselves about mindfulness techniques, and consider reserving some time to develop mindfulness skills.
Monday, October 19, 2009
The Importance of Two-Sided Arguments
This is a topic I was meaning to write a post about for some time. I encountered this topic while doing some social psychology reading last year, and it touches upon a lot of other posts I've written, having to do with decision-making and persuasion. It touches on the huge issue of bias which appears in so much of the medical and health literature.
Here is what some of the social psychology research has to say on this:
1) If someone already agrees on an issue, then a one-sided appeal is most effective. So, for example, if I happen to recommend a particular brand of toothpaste, or a particular political candidate, and I simply give a list of reasons why my particular recommendation is best, then I am usually "preaching to the converted." Perhaps more people will go out to buy that toothpaste brand, or vote for that candidate, but they would mostly be people who would have made those choices anyway. The only others who would be most persuaded by my advice would be those who do not have a strong personal investment or attachment to the issue.
2) If people are already aware of opposing arguments, a two-sided presentation is more persuasive and enduring. And if people disagree with a certain issue, a two-sided presentation is more persuasive to change their minds. People are likely to dismiss as biased a one-sided presentation which disagrees with their point of view, even if the presentation contains accurate and well-organized information. This is one of my complaints about various types of media and documentary styles: sometimes there is an overt left-wing or right-wing political bias that is immediately apparent, particularly to a person holding the opposing stance. I can think of numerous examples in local and international newspapers and television. The information from such media or documentary presentations would therefore have little educational or persuasive impact except with individuals who probably agree with the information and the point of view in advance. The strongest documentary or journalistic style has to be one which presents both sides of a debate, otherwise it is probably almost worthless to effect meaningful change--in fact it could entrench the points of view of opposing camps.
It has also been found that if people are already committed to a certain belief or position, than a mild attack or challenge of this position causes people to strengthen their initial position. Ineffective persuasion may "inoculate" people attitudinally, causing them to be more committed to their initial positions. In an educational sense, children could be "inoculated" against negative persuasion, such as from television ads or peer pressure to smoke, etc. by exploring, analyzing, and discussing such persuasive tactics, with parents or teachers.
However, such "inoculation" may be an instrument of attitudinal entrenchment and stubbornness: a person who has anticipated arguments against his or her committed position is more likely to hold that position more tenaciously. Or an individual who has been taught a delusional belief system may have been taught the various challenges to the belief system to expect: this may "inoculate" the person against challenging this belief system, and cause the delusions to become more entrenched.
An adversarial justice system reminds me to some degree of an efficient process, from a psychological point of view, to seek the least biased truth. However, the problem here is that both sides "inoculate" themselves against the evidence presented by the other. The opposing camps do not seek "resolution"--they seek to win, which is quite different. Also, the prosecution and the defense do not EACH present a balanced analysis of pro & con regarding their cases. There is information possibly withheld--the defense may truly know the guilt of the accused, yet this may not be shared openly in court. Presumably the prosecution would not prosecute if the innocence of the accused was known for sure.
Here are some applications of these ideas, which I think are relevant in psychiatry:
1) Depression, anxiety, and other types of mental illness, tend to feature entrenched thinking. Thoughts which are very negative, hostile, or pessimistic--about self, world, or future--may have been consolidated over a period of years or decades, often reinforced by negative experiences. In this setting, one-sided optimistic advice--even if accurate-- could be very counterproductive. It could further entrench the depressive cognitive stance. Standard "Burns style" cognitive therapy can also be excessively "rosy", in my opinion, and may be very ineffective for similar reasons. I think of the smiling picture of the author on the cover of a cognitive therapy workbook as an instant turn-off (for many) which would understandably strengthen the consolidation of many chronic depressive thoughts.
But I do think that a cognitive therapy approach could be very helpful, provided it includes the depressive or negative thinking in an honest, thorough, systematic debate or dialectic. That is, the work has to involve "two-sided argument".
2) In medical literature, there is a great deal of bias going on. Many of my previous postings have been about this. On other internet sites, there are various points of view, some of which are quite extreme. Those sites which are invariably about "pharmaceutical industry bias", etc. I think are actually quite ineffectual, if they merely are covering the same theme, over and over again. They are likely to be sites which are "preaching to the converted", and are likely to be viewed as themselves biased or extreme by someone looking for balanced advice. They may cause individuals with an already biased point of view to unreasonably entrench their positions further.
Also, I suspect the authors of sites like this, may themselves have become quite biased. If their site has repeatedly criticized the inadequacy of the research data about some drug intended to treat depression or bipolar disorder, etc., they may be less likely to consider or publish contrary evidence that the drug actually works. Once we commit ourselves to a position, we all have a tendency to cling to that position, even when evidence should sway us.
On the other hand, if there is a site which consistently gives medication advice of one sort or the other, I think it is unlikely to change very many opinions on this issue, except among those who are already trying out different medications.
So, in my opinion, it is a healthy practice when analyzing issues, including health care decisions, to carefully consider both sides of an argument. If the issue has to do with a treatment, including a medication, a style of psychotherapy, an alternative health care modality, or of doing nothing at all, then I encourage the habit of analyzing the evidence in two ways:
1) gather all evidence which supports the modality
2) gather all evidence which opposes it
Then I encourage a weighing, and a synthesis, of these points of view, before making a decision.
I think that this is the most reliable way to minimize biases. If such a system is applied to one's own attitudes, thoughts, values, and behaviours, I think it is the most effective to promote change and growth.
References:
Myers, David. Social Psychology, fourth edition. New York: McGraw-Hill; 1993. p. 275; 294-297.
Here is what some of the social psychology research has to say on this:
1) If someone already agrees on an issue, then a one-sided appeal is most effective. So, for example, if I happen to recommend a particular brand of toothpaste, or a particular political candidate, and I simply give a list of reasons why my particular recommendation is best, then I am usually "preaching to the converted." Perhaps more people will go out to buy that toothpaste brand, or vote for that candidate, but they would mostly be people who would have made those choices anyway. The only others who would be most persuaded by my advice would be those who do not have a strong personal investment or attachment to the issue.
2) If people are already aware of opposing arguments, a two-sided presentation is more persuasive and enduring. And if people disagree with a certain issue, a two-sided presentation is more persuasive to change their minds. People are likely to dismiss as biased a one-sided presentation which disagrees with their point of view, even if the presentation contains accurate and well-organized information. This is one of my complaints about various types of media and documentary styles: sometimes there is an overt left-wing or right-wing political bias that is immediately apparent, particularly to a person holding the opposing stance. I can think of numerous examples in local and international newspapers and television. The information from such media or documentary presentations would therefore have little educational or persuasive impact except with individuals who probably agree with the information and the point of view in advance. The strongest documentary or journalistic style has to be one which presents both sides of a debate, otherwise it is probably almost worthless to effect meaningful change--in fact it could entrench the points of view of opposing camps.
It has also been found that if people are already committed to a certain belief or position, than a mild attack or challenge of this position causes people to strengthen their initial position. Ineffective persuasion may "inoculate" people attitudinally, causing them to be more committed to their initial positions. In an educational sense, children could be "inoculated" against negative persuasion, such as from television ads or peer pressure to smoke, etc. by exploring, analyzing, and discussing such persuasive tactics, with parents or teachers.
However, such "inoculation" may be an instrument of attitudinal entrenchment and stubbornness: a person who has anticipated arguments against his or her committed position is more likely to hold that position more tenaciously. Or an individual who has been taught a delusional belief system may have been taught the various challenges to the belief system to expect: this may "inoculate" the person against challenging this belief system, and cause the delusions to become more entrenched.
An adversarial justice system reminds me to some degree of an efficient process, from a psychological point of view, to seek the least biased truth. However, the problem here is that both sides "inoculate" themselves against the evidence presented by the other. The opposing camps do not seek "resolution"--they seek to win, which is quite different. Also, the prosecution and the defense do not EACH present a balanced analysis of pro & con regarding their cases. There is information possibly withheld--the defense may truly know the guilt of the accused, yet this may not be shared openly in court. Presumably the prosecution would not prosecute if the innocence of the accused was known for sure.
Here are some applications of these ideas, which I think are relevant in psychiatry:
1) Depression, anxiety, and other types of mental illness, tend to feature entrenched thinking. Thoughts which are very negative, hostile, or pessimistic--about self, world, or future--may have been consolidated over a period of years or decades, often reinforced by negative experiences. In this setting, one-sided optimistic advice--even if accurate-- could be very counterproductive. It could further entrench the depressive cognitive stance. Standard "Burns style" cognitive therapy can also be excessively "rosy", in my opinion, and may be very ineffective for similar reasons. I think of the smiling picture of the author on the cover of a cognitive therapy workbook as an instant turn-off (for many) which would understandably strengthen the consolidation of many chronic depressive thoughts.
But I do think that a cognitive therapy approach could be very helpful, provided it includes the depressive or negative thinking in an honest, thorough, systematic debate or dialectic. That is, the work has to involve "two-sided argument".
2) In medical literature, there is a great deal of bias going on. Many of my previous postings have been about this. On other internet sites, there are various points of view, some of which are quite extreme. Those sites which are invariably about "pharmaceutical industry bias", etc. I think are actually quite ineffectual, if they merely are covering the same theme, over and over again. They are likely to be sites which are "preaching to the converted", and are likely to be viewed as themselves biased or extreme by someone looking for balanced advice. They may cause individuals with an already biased point of view to unreasonably entrench their positions further.
Also, I suspect the authors of sites like this, may themselves have become quite biased. If their site has repeatedly criticized the inadequacy of the research data about some drug intended to treat depression or bipolar disorder, etc., they may be less likely to consider or publish contrary evidence that the drug actually works. Once we commit ourselves to a position, we all have a tendency to cling to that position, even when evidence should sway us.
On the other hand, if there is a site which consistently gives medication advice of one sort or the other, I think it is unlikely to change very many opinions on this issue, except among those who are already trying out different medications.
So, in my opinion, it is a healthy practice when analyzing issues, including health care decisions, to carefully consider both sides of an argument. If the issue has to do with a treatment, including a medication, a style of psychotherapy, an alternative health care modality, or of doing nothing at all, then I encourage the habit of analyzing the evidence in two ways:
1) gather all evidence which supports the modality
2) gather all evidence which opposes it
Then I encourage a weighing, and a synthesis, of these points of view, before making a decision.
I think that this is the most reliable way to minimize biases. If such a system is applied to one's own attitudes, thoughts, values, and behaviours, I think it is the most effective to promote change and growth.
References:
Myers, David. Social Psychology, fourth edition. New York: McGraw-Hill; 1993. p. 275; 294-297.
Monday, October 5, 2009
Pregnancy & Depressive Relapse
I was looking at an article in JAMA from 2006, which was about pregnant women taking antidepressants. They were followed through pregnancy, and depressive relapses were related to changes in antidepressant dose. Here's a link to the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/16449615
The study is too weakly designed to allow strong conclusions. Yet the abstract makes a statement about "pregnancy not being protective" which--while possibly true--is not directly related to the findings from the study. This criticism was wisely conceived by the author of "The Last Psychiatrist" blog:
http://thelastpsychiatrist.com/2006/10/jama_deludes.html
Yet the JAMA study is not uninformative.
And the criticism mentioned above goes a bit too far, in my opinion. The critique itself makes overly strong statements in its own title & abstract.
It appears quite clear that pregnant women with a history of depressive illness, who are taking antidepressants, but decrease or discontinue their medication during the pregnancy, have a substantially higher risk of depressive relapse.
Because the study was not randomized, we cannot know for sure that this association is causal. But causation would be reasonably suggested. It does not seem likely that this large effect would have been caused by women whose "unstable" depressive symptoms led them to discontinue their antidepressants (i.e. it does not seem likely to me that "reverse causation" would be a prominent cause for this finding). I think this could happen in some cases, but not frequently. Nor does it seem likely to me that a woman already taking an antidepressant, who becomes more depressed during the pregnancy, would therefore stop taking her medication. This, too, could happen (I can think of clinical examples), but I don't think it would be common. It seems most likely to me that the causation is quite simple: stabilized depressive illness during pregnancy is likely to become less stable, and more prone to relapse, if antidepressant medication is discontinued.
The critique of this article also discusses the fact that women in the study who increased their doses of medication also had higher rates of depressive relapse, yet this fact is not mentioned very much in the abstract or conclusion. This finding is also not surprising--what other reason would a pregnant woman have to increase a dose of medication which she was already taking during her pregnancy, other than an escalation of symptoms? In this case, depressive relapse (which can happen despite medication treatment) is likely the cause of the increased dose--the increased dose is unlikely to have caused the depressive relapse.
Yet, as I said above, the study only allows us to infer these conclusions, as it was not randomized. And I agree that the authors overstate their conclusions in the abstract. In order to more definitively answer these questions, a randomized prospective study would need to be done.
http://www.ncbi.nlm.nih.gov/pubmed/16449615
The study is too weakly designed to allow strong conclusions. Yet the abstract makes a statement about "pregnancy not being protective" which--while possibly true--is not directly related to the findings from the study. This criticism was wisely conceived by the author of "The Last Psychiatrist" blog:
http://thelastpsychiatrist.com/2006/10/jama_deludes.html
Yet the JAMA study is not uninformative.
And the criticism mentioned above goes a bit too far, in my opinion. The critique itself makes overly strong statements in its own title & abstract.
It appears quite clear that pregnant women with a history of depressive illness, who are taking antidepressants, but decrease or discontinue their medication during the pregnancy, have a substantially higher risk of depressive relapse.
Because the study was not randomized, we cannot know for sure that this association is causal. But causation would be reasonably suggested. It does not seem likely that this large effect would have been caused by women whose "unstable" depressive symptoms led them to discontinue their antidepressants (i.e. it does not seem likely to me that "reverse causation" would be a prominent cause for this finding). I think this could happen in some cases, but not frequently. Nor does it seem likely to me that a woman already taking an antidepressant, who becomes more depressed during the pregnancy, would therefore stop taking her medication. This, too, could happen (I can think of clinical examples), but I don't think it would be common. It seems most likely to me that the causation is quite simple: stabilized depressive illness during pregnancy is likely to become less stable, and more prone to relapse, if antidepressant medication is discontinued.
The critique of this article also discusses the fact that women in the study who increased their doses of medication also had higher rates of depressive relapse, yet this fact is not mentioned very much in the abstract or conclusion. This finding is also not surprising--what other reason would a pregnant woman have to increase a dose of medication which she was already taking during her pregnancy, other than an escalation of symptoms? In this case, depressive relapse (which can happen despite medication treatment) is likely the cause of the increased dose--the increased dose is unlikely to have caused the depressive relapse.
Yet, as I said above, the study only allows us to infer these conclusions, as it was not randomized. And I agree that the authors overstate their conclusions in the abstract. In order to more definitively answer these questions, a randomized prospective study would need to be done.
Wednesday, September 16, 2009
Perils of Positive Thinking?
Joanne Wood et al. had an article published in Psychological Science in June 2009. It was a study in which subjects with low self-esteem felt worse after doing various "positive thinking" exercises. Subjects with higher self-esteem felt better with self-affirming statements.
Here is a link to the abstract: http://www.ncbi.nlm.nih.gov/pubmed/19493324
So the study seems to suggest that it could be detrimental to engage in "positive thinking" if you are already having depressive thoughts, or negative thoughts about yourself or your situation. The authors theorize that if you if have a negative view of yourself, then it may simply draw more attention in your mind to your own negative self-view, if you force yourself to make a positive statement about yourself. The positive statement may simply seem ridiculous, unrealistic, unattainable, perhaps a reminder of something you don't have or feel that you cannot ever have.
However, the study is weak, and demonstrates something that most of us could see to be obviously true. The study is cross-sectional, and looks at the effect of a single episode of forced "positive thinking." This is like measuring the effect of marathon training after one single workout, and finding that those already in good shape really enjoyed their workout, while those who hadn't run before felt awful afterward.
Any exercise to change one's mind has to be practiced and repeated over a period of months or years. A single bout of exercise will usually accomplish very little. In fact, it will probably lead to soreness or injury, especially if the exercise is too far away from your current fitness level. I suppose if the initial "exercise" is a gentle and encouraging introduction, without overdoing it, then much more could be accomplished, as it could get one started into a new habit, and encourage hope.
"Positive thinking" exercises would, in my opinion, have to feel realistic and honest in order to be helpful. They may feel somewhat contrived, but I think this is also normal, just as phrases in a new language may initially feel contrived as you practice them.
And, following a sort of language-learning or athletic metaphor again, I think that "positive thinking" exercises cannot simply be repeating trite phrases such as "I am a good person!" Rather, they need to be dialogs in your mind, or with other people -- in which you challenge yourself to generate self-affirming statements, perhaps then listen to your mind rail against them, then generate a new affirming response. It becomes an active conversation in your mind rather than bland repetition of statements you don't find meaningful. This is just like how learning a language requires active conversation.
Self-affirmation may initially be yet another tool which at times helps you get through the hour or the day. But I believe that self-affirming language will gradually become incorporated deeply into your identity, as you practice daily, over a period of years. Actually, I think the "language" itself is not entirely the source of identity change; I think such language acts as a catalyst which resonates with a core of positive identity which already exists within you, and allows it to develop and grow with greater ease. This core of positivity may have been suppressed due to years of depression, environmental adversity, or other stresses.
Here is a link to the abstract: http://www.ncbi.nlm.nih.gov/pubmed/19493324
So the study seems to suggest that it could be detrimental to engage in "positive thinking" if you are already having depressive thoughts, or negative thoughts about yourself or your situation. The authors theorize that if you if have a negative view of yourself, then it may simply draw more attention in your mind to your own negative self-view, if you force yourself to make a positive statement about yourself. The positive statement may simply seem ridiculous, unrealistic, unattainable, perhaps a reminder of something you don't have or feel that you cannot ever have.
However, the study is weak, and demonstrates something that most of us could see to be obviously true. The study is cross-sectional, and looks at the effect of a single episode of forced "positive thinking." This is like measuring the effect of marathon training after one single workout, and finding that those already in good shape really enjoyed their workout, while those who hadn't run before felt awful afterward.
Any exercise to change one's mind has to be practiced and repeated over a period of months or years. A single bout of exercise will usually accomplish very little. In fact, it will probably lead to soreness or injury, especially if the exercise is too far away from your current fitness level. I suppose if the initial "exercise" is a gentle and encouraging introduction, without overdoing it, then much more could be accomplished, as it could get one started into a new habit, and encourage hope.
"Positive thinking" exercises would, in my opinion, have to feel realistic and honest in order to be helpful. They may feel somewhat contrived, but I think this is also normal, just as phrases in a new language may initially feel contrived as you practice them.
And, following a sort of language-learning or athletic metaphor again, I think that "positive thinking" exercises cannot simply be repeating trite phrases such as "I am a good person!" Rather, they need to be dialogs in your mind, or with other people -- in which you challenge yourself to generate self-affirming statements, perhaps then listen to your mind rail against them, then generate a new affirming response. It becomes an active conversation in your mind rather than bland repetition of statements you don't find meaningful. This is just like how learning a language requires active conversation.
Self-affirmation may initially be yet another tool which at times helps you get through the hour or the day. But I believe that self-affirming language will gradually become incorporated deeply into your identity, as you practice daily, over a period of years. Actually, I think the "language" itself is not entirely the source of identity change; I think such language acts as a catalyst which resonates with a core of positive identity which already exists within you, and allows it to develop and grow with greater ease. This core of positivity may have been suppressed due to years of depression, environmental adversity, or other stresses.
Friday, September 11, 2009
Making it through a difficult day or night
It can be hard to make it through the next hour, if you are feeling desperately unhappy, agitated, empty, worthless, or isolated, especially if you also feel disconnected from love, meaning, community, "belongingness," or relationships with others.
Such desperate places of mind can yet be familiar places, and a certain set of coping tactics may evolve. Sometimes social isolation or sleep can help the time pass; other times there can be addictive or compulsive behaviours of different sorts. These tactics may either be distractions from pain or distress, or may serve to anesthetize the symptoms in some way, to help the time pass.
Time can become an oppressive force to be battled continuously, one minute after the next.
I'd like to work on a set of ideas to help with situations like this. I realize a lot of these ideas may be things that are already very familiar, or that may seem trite or irrelevant. Maybe things that are much easier said than done. But I'd like to just sort of brainstorm here for a moment:
1) One of the most important things, I think, is to be able to hold onto something positive or good (large or small), in your mind, to focus on it, to rehearse it, to nurture its mental image, even if that good thing is not immediately present. The "good thing" could be anything -- a friend or loved one, a song, a place, a memory, a sensation, a dream, a goal, an idea. In the darkest of moments we are swept into the immediacy of suffering, and may lose touch with the internalized anchors which might help us to hold on, or to help us direct our behaviour safely through the next 24 hours.
In order to practice "holding on" I guess one would have to get over the skepticism many would have that such a tactic could actually help.
In order to address that, I would say that "covert imagery" is a well-established technique, with an evidence base in such areas as the treatment of phobias, learning new physical activities, practicing skills, even athletic training (imagining doing reps will actually strengthen muscles). The pianist Glenn Gould used covert imagery to practice the piano, and preferred to do much of his practice and rehearsal away from any keyboard; he preferred to learn new pieces entirely away from the piano. There is nothing mystical about the technique -- it is just a different way of exercising your brain, and therefore your body (which is an extension of your brain).
In order for covert imagery to work, it really does help to believe in it though (skepticism is highly demotivating).
Relationships can be "covertly imagined" as well -- and I think this is a great insight from the psychoanalysts. An internalized positive relationship can stay with us, consciously or unconsciously, even when we are physically alone. If you have not had many positive relationships, or your relationships have not been trustworthy, safe, or stable, then you may not have a positive internalized relationship to comfort you when you are in distress. You may feel comforted in the moment, if the situation is right, but when alone, you may be right back to a state of loneliness or torment.
The more trust and closeness that develops in your relationship life, the easier it will be to self-soothe, as you "internalize" these relationships.
Here are some ways to develop these ideas in practical ways:
-journaling, not just about distress, but about any healthy relationship or force in your life which helps soothe you and comfort you
-using healthy "transitional objects" which symbolize things which are soothing or comforting, without those things literally being present. These objects may serve to cue your memory, and help interrupt a cycle of depressive thinking or action.
-if there is a healthy, positive, or soothing relationship with someone in your life, imagine what that person might say to comfort or guide you in the present moment; and "save up" or "put aside" some of your immediate distress to discuss with that person when you next meet.
2) Healthy distraction.
e.g. music (listening or performing); reading (silently or aloud, or being read to); exercise (in healthy moderation); hobbies (e.g. crafts, knitting, art); baking
-consider starting a new hobby (e.g. photography)
3) Planning healthy structured activities
e.g. with community centres, organized hikes, volunteering, deliberately and consciously phoning friends
4) Creating healthy comforts
e.g. hot baths, aromatherapy, getting a massage, preparing or going out for a nice meal
5) Recognizing and blocking addictive behaviours
-there may be a lot of ambivalence about this, as the addictive behaviours may have a powerful or important role in your life; but freeing oneself from an addiction, or from recurrent harmful behaviour patterns, can be one of the most satisfying and liberating of therapeutic life changes.
An addictive process often "convinces" one that its presence is necessary and helpful, and that its absence would cause even worse distress.
6) Humour
-can anyone or anything make you laugh?
-can you make someone laugh?
7) Meditation
-takes a lot of practice, but can be a powerful tool for dealing safely with extreme pain
-could start with a few Kabat-Zinn books & tapes, or consider taking a class or seminar (might need to be patient to find a variety of meditation which suits you)
8) Being with animals (dogs, cats, horses, etc.). If you don't or can't have a pet, then volunteering with animals (e.g. at the SPCA) could be an option.
9) Caring for other living things (e.g. pets, plants, gardens)
10) Arranging for someone else to take care of you for a while (e.g. by friends, family, or in hospital if necessary)
11) Visiting psychiatry blogs
-(in moderation)
...I'm just writing this on the spur of the moment, I'll have to do some editing later, feel free to comment...
Such desperate places of mind can yet be familiar places, and a certain set of coping tactics may evolve. Sometimes social isolation or sleep can help the time pass; other times there can be addictive or compulsive behaviours of different sorts. These tactics may either be distractions from pain or distress, or may serve to anesthetize the symptoms in some way, to help the time pass.
Time can become an oppressive force to be battled continuously, one minute after the next.
I'd like to work on a set of ideas to help with situations like this. I realize a lot of these ideas may be things that are already very familiar, or that may seem trite or irrelevant. Maybe things that are much easier said than done. But I'd like to just sort of brainstorm here for a moment:
1) One of the most important things, I think, is to be able to hold onto something positive or good (large or small), in your mind, to focus on it, to rehearse it, to nurture its mental image, even if that good thing is not immediately present. The "good thing" could be anything -- a friend or loved one, a song, a place, a memory, a sensation, a dream, a goal, an idea. In the darkest of moments we are swept into the immediacy of suffering, and may lose touch with the internalized anchors which might help us to hold on, or to help us direct our behaviour safely through the next 24 hours.
In order to practice "holding on" I guess one would have to get over the skepticism many would have that such a tactic could actually help.
In order to address that, I would say that "covert imagery" is a well-established technique, with an evidence base in such areas as the treatment of phobias, learning new physical activities, practicing skills, even athletic training (imagining doing reps will actually strengthen muscles). The pianist Glenn Gould used covert imagery to practice the piano, and preferred to do much of his practice and rehearsal away from any keyboard; he preferred to learn new pieces entirely away from the piano. There is nothing mystical about the technique -- it is just a different way of exercising your brain, and therefore your body (which is an extension of your brain).
In order for covert imagery to work, it really does help to believe in it though (skepticism is highly demotivating).
Relationships can be "covertly imagined" as well -- and I think this is a great insight from the psychoanalysts. An internalized positive relationship can stay with us, consciously or unconsciously, even when we are physically alone. If you have not had many positive relationships, or your relationships have not been trustworthy, safe, or stable, then you may not have a positive internalized relationship to comfort you when you are in distress. You may feel comforted in the moment, if the situation is right, but when alone, you may be right back to a state of loneliness or torment.
The more trust and closeness that develops in your relationship life, the easier it will be to self-soothe, as you "internalize" these relationships.
Here are some ways to develop these ideas in practical ways:
-journaling, not just about distress, but about any healthy relationship or force in your life which helps soothe you and comfort you
-using healthy "transitional objects" which symbolize things which are soothing or comforting, without those things literally being present. These objects may serve to cue your memory, and help interrupt a cycle of depressive thinking or action.
-if there is a healthy, positive, or soothing relationship with someone in your life, imagine what that person might say to comfort or guide you in the present moment; and "save up" or "put aside" some of your immediate distress to discuss with that person when you next meet.
2) Healthy distraction.
e.g. music (listening or performing); reading (silently or aloud, or being read to); exercise (in healthy moderation); hobbies (e.g. crafts, knitting, art); baking
-consider starting a new hobby (e.g. photography)
3) Planning healthy structured activities
e.g. with community centres, organized hikes, volunteering, deliberately and consciously phoning friends
4) Creating healthy comforts
e.g. hot baths, aromatherapy, getting a massage, preparing or going out for a nice meal
5) Recognizing and blocking addictive behaviours
-there may be a lot of ambivalence about this, as the addictive behaviours may have a powerful or important role in your life; but freeing oneself from an addiction, or from recurrent harmful behaviour patterns, can be one of the most satisfying and liberating of therapeutic life changes.
An addictive process often "convinces" one that its presence is necessary and helpful, and that its absence would cause even worse distress.
6) Humour
-can anyone or anything make you laugh?
-can you make someone laugh?
7) Meditation
-takes a lot of practice, but can be a powerful tool for dealing safely with extreme pain
-could start with a few Kabat-Zinn books & tapes, or consider taking a class or seminar (might need to be patient to find a variety of meditation which suits you)
8) Being with animals (dogs, cats, horses, etc.). If you don't or can't have a pet, then volunteering with animals (e.g. at the SPCA) could be an option.
9) Caring for other living things (e.g. pets, plants, gardens)
10) Arranging for someone else to take care of you for a while (e.g. by friends, family, or in hospital if necessary)
11) Visiting psychiatry blogs
-(in moderation)
...I'm just writing this on the spur of the moment, I'll have to do some editing later, feel free to comment...
Wednesday, July 29, 2009
Low-dose atypical antipsychotics for treating non-psychotic anxiety or mood symptoms
Atypical antipsychotics are frequently prescribed to treat symptoms of anxiety and depression. They can be used in the treatment of generalized anxiety, panic disorder, OCD, major depressive disorder, PTSD, bipolar disorder, personality disorders, etc. At this point, such use could be considered "off-label", since the primary use of antipsychotics is treating schizophrenia or major mood disorders with psychotic features.
But there is an expanding evidence base showing that atypicals can be useful in "off-label" situations. Here is a brief review of some of the studies:
http://www.ncbi.nlm.nih.gov/pubmed/19470174
{this is a good recent study comparing low-dose risperidone -- about 0.5 mg -- with paroxetine, for treating panic disorder over 8 weeks. The risperidone group did well, with equal or better symptom relief, also possibly faster onset. But 8 weeks is very brief -- it would be important to look at results over a year or more, and to assess the possibility of withdrawal or rebound symptoms if the medication is stopped. Also is would be important to determine if the medication is synergistic with psychological therapies, or whether it could undermine psychological therapy (there is some evidence that benzodiazepines may undermine the effectiveness of psychological therapies) }
http://www.ncbi.nlm.nih.gov/pubmed/16649823
{an open study from 2006 showing significant improvements in anxiety when low doses of risperidone, of about 1 mg, were added to an antidepressant, over an 8 week trial}
http://www.ncbi.nlm.nih.gov/pubmed/18455360
{this 2008 study shows significant improvement in generalized anxiety with 12 weeks of adjunctive quetiapine. It was not "low-dose" though -- the average dose was almost 400 mg per day. There is potential bias in this study due to conflict-of-interest, also there was no adjunctive placebo group}
http://www.ncbi.nlm.nih.gov/pubmed/16889446
{in this 2006 study. patients with a borderline personality diagnosis were given quetiapine 200-400 mg daily, for a 12 week trial. As I look at the results in the article itself, I see that the most substantial improvement was in anxiety symptoms, without much change in other symptom areas. The authors state that patients with prominent impulsive or aggressive symptoms responded best}
http://www.ncbi.nlm.nih.gov/pubmed/17110817
{in this large 2006 study (the BOLDER II study), quetiapine alone was used to treat bipolar depression. Doses were 300 mg/d, 600 mg/d, or placebo. There was significant, clinically relevant improvement in the quetiapine groups, with the 300 mg group doing best. Improvements were in anxiety symptoms, depressive symptoms, suicidal ideation, sleep, and overall quality of life.}
Here's a reference to a lengthy and detailed report from the FDA about quetiapine safety when used to treat depression or anxiety:
http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4424b2-01-FDA.pdf
In summary, I support the use of atypical antipsychotics as adjuncts for treating various symptoms including anxiety, irritability, etc. But as with any treatment (or non-treatment), there needs to be a close review of benefits vs. risks. The risks of using antipsychotics for treating anxiety are probably underestimated, because the existing studies are of such short duration. Also the benefits over long-term use are not clearly established either.
For risk data, it would be relevant to look at groups who have taken antipsychotics for long periods of time. In this group, antipsychotic use is associated with reduced mortality rates (see the following 2009 reference from Lancet: http://www.ncbi.nlm.nih.gov/pubmed/19595447, which looks at a cohort of over 60 000 schizophrenic patients, showing reduced mortality rates in those who took antipsychotics long-term, compared to those taking shorter courses of antipsychotics, or none at all--the mortality rate was most dramatically reduced in those taking clozapine. Overall, the life expectancy of schizophrenic patients was shown to have increased over a 10-year period, alongside substantial increases in atypical antipsychotic use)
It is certainly clear to me that all other treatments for anxiety (especially behavioural therapies, lifestyle changes, other forms of psychotherapy) be optimized, in an individualized way, before medication adjuncts be used.
But I recognize that suffering from anxiety or other psychiatric symptoms can be severely debilitating, can delay or obstruct progress in relationships, work, school, quality of life, etc. The risks of non-treatment should be taken very seriously. My view of the existing evidence is that adjunctive low-dose antipsychotics can have significant benefits, which can outweigh risks for many patients with non-psychotic disorders. As with any medical treatment decision, it is important for you and your physician to regularly monitor or discuss risks vs. benefits of ongoing medication therapies, and be open to discuss new evidence which is coming out.
But there is an expanding evidence base showing that atypicals can be useful in "off-label" situations. Here is a brief review of some of the studies:
http://www.ncbi.nlm.nih.gov/pubmed/19470174
{this is a good recent study comparing low-dose risperidone -- about 0.5 mg -- with paroxetine, for treating panic disorder over 8 weeks. The risperidone group did well, with equal or better symptom relief, also possibly faster onset. But 8 weeks is very brief -- it would be important to look at results over a year or more, and to assess the possibility of withdrawal or rebound symptoms if the medication is stopped. Also is would be important to determine if the medication is synergistic with psychological therapies, or whether it could undermine psychological therapy (there is some evidence that benzodiazepines may undermine the effectiveness of psychological therapies) }
http://www.ncbi.nlm.nih.gov/pubmed/16649823
{an open study from 2006 showing significant improvements in anxiety when low doses of risperidone, of about 1 mg, were added to an antidepressant, over an 8 week trial}
http://www.ncbi.nlm.nih.gov/pubmed/18455360
{this 2008 study shows significant improvement in generalized anxiety with 12 weeks of adjunctive quetiapine. It was not "low-dose" though -- the average dose was almost 400 mg per day. There is potential bias in this study due to conflict-of-interest, also there was no adjunctive placebo group}
http://www.ncbi.nlm.nih.gov/pubmed/16889446
{in this 2006 study. patients with a borderline personality diagnosis were given quetiapine 200-400 mg daily, for a 12 week trial. As I look at the results in the article itself, I see that the most substantial improvement was in anxiety symptoms, without much change in other symptom areas. The authors state that patients with prominent impulsive or aggressive symptoms responded best}
http://www.ncbi.nlm.nih.gov/pubmed/17110817
{in this large 2006 study (the BOLDER II study), quetiapine alone was used to treat bipolar depression. Doses were 300 mg/d, 600 mg/d, or placebo. There was significant, clinically relevant improvement in the quetiapine groups, with the 300 mg group doing best. Improvements were in anxiety symptoms, depressive symptoms, suicidal ideation, sleep, and overall quality of life.}
Here's a reference to a lengthy and detailed report from the FDA about quetiapine safety when used to treat depression or anxiety:
http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4424b2-01-FDA.pdf
In summary, I support the use of atypical antipsychotics as adjuncts for treating various symptoms including anxiety, irritability, etc. But as with any treatment (or non-treatment), there needs to be a close review of benefits vs. risks. The risks of using antipsychotics for treating anxiety are probably underestimated, because the existing studies are of such short duration. Also the benefits over long-term use are not clearly established either.
For risk data, it would be relevant to look at groups who have taken antipsychotics for long periods of time. In this group, antipsychotic use is associated with reduced mortality rates (see the following 2009 reference from Lancet: http://www.ncbi.nlm.nih.gov/pubmed/19595447, which looks at a cohort of over 60 000 schizophrenic patients, showing reduced mortality rates in those who took antipsychotics long-term, compared to those taking shorter courses of antipsychotics, or none at all--the mortality rate was most dramatically reduced in those taking clozapine. Overall, the life expectancy of schizophrenic patients was shown to have increased over a 10-year period, alongside substantial increases in atypical antipsychotic use)
It is certainly clear to me that all other treatments for anxiety (especially behavioural therapies, lifestyle changes, other forms of psychotherapy) be optimized, in an individualized way, before medication adjuncts be used.
But I recognize that suffering from anxiety or other psychiatric symptoms can be severely debilitating, can delay or obstruct progress in relationships, work, school, quality of life, etc. The risks of non-treatment should be taken very seriously. My view of the existing evidence is that adjunctive low-dose antipsychotics can have significant benefits, which can outweigh risks for many patients with non-psychotic disorders. As with any medical treatment decision, it is important for you and your physician to regularly monitor or discuss risks vs. benefits of ongoing medication therapies, and be open to discuss new evidence which is coming out.
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