There have been a variety of studies in the literature showing that pregabalin is effective for treating generalized anxiety.
The latest of such studies I have seen is published by Mark Boschen in the September 2011 issue of The Canadian Journal of Psychiatry (p.558-565).
This article is a meta-analysis, and shows generally that pregabalin is effective compared to placebo, and has similar, if not greater, effectiveness than other medication options for treating generalized anxiety, such as SSRIs, venlafaxine, and benzodiazepines.
The most common doses have been in the 600 mg/day range, which I consider quite high, particularly since a reasonable dose range for pregabalin could be around 75-300 mg/day.
The "limitations" admitted by the author include issues about dosing, and the fact that Pfizer has funded every published randomized study quoted in the article.
I believe that pregabalin could be a very useful option to try, if a medication trial is being considered for generalized anxiety treatment (of course, the first lines of therapy for generalized anxiety are CBT, relaxation-oriented therapies, meditation, exercise, etc.--but for many people these approaches are not sufficiently helpful). Pregabalin has the advantage of having a quite different--and generally mild--side effect profile compared to other medications, and a what appears to be a fairly low (but I do not think zero) risk of addictiveness/dependence problems, particularly compared to benzodiazepines.
However -- the most obvious limitation of the literature findings is only mentioned briefly in passing by the author in the discussion: it is hard to make a good conclusion about a treatment for anxiety when the duration of follow-up is only 4-8 weeks! I believe that a study for this problem needs to extend for a year or more. First of all, many treatments for anxiety can be acutely helpful, but then wear off substantially over time. Arguably, having a beer every 4 hours could reduce GAD scores over a 4-week trial--but obviously this is not an acceptable long-term treatment! (not only would there be multiple physical harms caused by this over a period of many months or years, but there would be substantial tolerance to anxiety reduction effects, which might only become apparent over many months; furthermore,there would be new psychiatric symptoms induced over a period of months and beyond).
It is not clear from the literature whether the acute benefits over 4-8 weeks from pregabalin would persist over a year or more, whether there would be tolerance, whether there would be longer-term emergent physical or psychiatric side-effects, dependence phenomena, trouble with withdrawal or discontinuation, etc.
Research of this type could be used --spuriously--to justify giving GAD patients benzodiazepines on a routine basis as well, despite the frequent and obvious problem of tolerance, dependence, cognitive problems, etc. Most benzodiazepine studies are of similarly short duration, hence have very limited value to guide us for the long-term treatment decisions which are most important.
Yet, I do think that pregabalin is promising, and could be worth a cautious try, particularly if other approaches are not working well.
Friday, September 30, 2011
Thursday, September 29, 2011
Multi-dimensional nature of borderline personality symptom structure
Chmielewski et al. have published an article in the September 2011 edition of the Canadian Journal of Psychiatry in which they show that borderline personality is better described as having several separate symptom dimensions.
The benefit of having several dimensions instead of one could be illustrated by way of analogy: suppose we are talking about heart disease. One could simply describe all patients suffering a "heart attack" according to a single severity scale, perhaps including information of the amount of pain, degree of disability afterwards, etc. This scale could be quite useful, but it would obscure a great deal of information about the group, and reduce the efficiency of treatment. A multi-dimensional scale would instead look at several domains separately, such as perfusion abnormalities, rhythm abnormalities, and structural abnormalities. Abnormal perfusion might be treated specifically with bypass surgery, rhythm problems with a pacemaker, and structural problems with a valve replacement etc. Thus the management could become more meaningfully specific.
The authors of this paper about borderline personality show that a 3-factor model fit well to describe symptoms in borderline patients; a 1-dimensional model fit much more poorly. The 3 factors are "affective dysregulation," "behavioural dysregulation," and "disturbed relations." Affective dysregulation would refer to high intensity and lability of negative emotion, inappropriate anger, etc. Behavioural dysregulation would refer to self-injurious behaviour, excessive or out-of-control behaviours such as binge eating, or I might add any sort of chemical or behavioural addiction. Disturbed relations of course refers to interpersonal relationship problems. One could see that these three domains would each influence the others, but part of a theoretical model is to consider to what degree problems in each domain could be considered primary. (similarly, a blocked coronary artery would be a primary perfusion problem, but could in turn cause a secondary rhythm and structural problem in the heart).
A particularly relevant remark from the authors comes in the discussion: "...the current pattern of associations suggests that the glue that holds the BPD construct together may largely represent the general dysfunction or misery common across all forms of psychopathology and not just BPD." So, the authors are hinting that we could perhaps do away with the BPD construct altogether, without any loss of insight, and instead simply describe in succinct terms what the core symptoms are. This makes sense to me. I do believe that some of these core symptoms are extremely important to examine and address directly. "Affective dysregulation" would be almost automatically addressed in any therapy environment, and "relationship dysfunction" is perhaps the most frequent topic of discussion (and perhaps transferential work) done in therapy. But the "behavioural dysregulation"domain I think is not quite so well-addressed in much therapeutic work. I see this domain as the most common severe problem relatively more unique to those who fit into a "borderline personality" spectrum. It is my own view to consider this domain through a type of addiction-medicine lens, as a set of problems which are highly destructive and addictive behavioural habits, often engaged in to cope with other symptoms, but which become independent problems with time. This is similar to any other addiction; alcoholism, for example, may begin as alcohol consumption intended to calm nerves, deal with boredom, or to facilitate socialization, but in time becomes more and more a separate, self-contained behavioural and physiological addiction.
In my browsing through the literature as I was writing this post just now, I encountered a psychology master's thesis published online (by Edward Selby, M.Sc. 2007). Here's a link:
http://etd.lib.fsu.edu/theses/available/etd-07092007-164107/unrestricted/SelbyMastersThesisFinal.pdf
Selby makes the case well that negative emotional cascades leading to behavioural dyregulation are strongly fuelled by rumination. The events of behavioural dysregulation, such as self-injury, serve to distract one from the intense discomfort of rumination. Here is a quote from the conclusion:
"the findings of this study provide preliminary evidence for an
emotional cascade model of dysregulated behavior. In this model high levels of rumination may cause extremely intense states of negative affect, which result in dysregulated behaviors that distract from rumination and reduce that state of negative affect. This study specifically linked rumination to drinking to cope, binge-eating behaviors, reassurance seeking, and urgency, and it is likely that rumination is linked to a variety of other deregulated behaviors. "
Rumination, of course, is another phenomenon common to much "general dysfunction or misery." I am reminded how important it can be, as a practical therapeutic project with patients, to work on ways to move away from, or to let go of, rumination. (see my previous post on rumination: http://garthkroeker.blogspot.com/2011/08/chronic-pain-rumination.html)
The benefit of having several dimensions instead of one could be illustrated by way of analogy: suppose we are talking about heart disease. One could simply describe all patients suffering a "heart attack" according to a single severity scale, perhaps including information of the amount of pain, degree of disability afterwards, etc. This scale could be quite useful, but it would obscure a great deal of information about the group, and reduce the efficiency of treatment. A multi-dimensional scale would instead look at several domains separately, such as perfusion abnormalities, rhythm abnormalities, and structural abnormalities. Abnormal perfusion might be treated specifically with bypass surgery, rhythm problems with a pacemaker, and structural problems with a valve replacement etc. Thus the management could become more meaningfully specific.
The authors of this paper about borderline personality show that a 3-factor model fit well to describe symptoms in borderline patients; a 1-dimensional model fit much more poorly. The 3 factors are "affective dysregulation," "behavioural dysregulation," and "disturbed relations." Affective dysregulation would refer to high intensity and lability of negative emotion, inappropriate anger, etc. Behavioural dysregulation would refer to self-injurious behaviour, excessive or out-of-control behaviours such as binge eating, or I might add any sort of chemical or behavioural addiction. Disturbed relations of course refers to interpersonal relationship problems. One could see that these three domains would each influence the others, but part of a theoretical model is to consider to what degree problems in each domain could be considered primary. (similarly, a blocked coronary artery would be a primary perfusion problem, but could in turn cause a secondary rhythm and structural problem in the heart).
A particularly relevant remark from the authors comes in the discussion: "...the current pattern of associations suggests that the glue that holds the BPD construct together may largely represent the general dysfunction or misery common across all forms of psychopathology and not just BPD." So, the authors are hinting that we could perhaps do away with the BPD construct altogether, without any loss of insight, and instead simply describe in succinct terms what the core symptoms are. This makes sense to me. I do believe that some of these core symptoms are extremely important to examine and address directly. "Affective dysregulation" would be almost automatically addressed in any therapy environment, and "relationship dysfunction" is perhaps the most frequent topic of discussion (and perhaps transferential work) done in therapy. But the "behavioural dysregulation"domain I think is not quite so well-addressed in much therapeutic work. I see this domain as the most common severe problem relatively more unique to those who fit into a "borderline personality" spectrum. It is my own view to consider this domain through a type of addiction-medicine lens, as a set of problems which are highly destructive and addictive behavioural habits, often engaged in to cope with other symptoms, but which become independent problems with time. This is similar to any other addiction; alcoholism, for example, may begin as alcohol consumption intended to calm nerves, deal with boredom, or to facilitate socialization, but in time becomes more and more a separate, self-contained behavioural and physiological addiction.
In my browsing through the literature as I was writing this post just now, I encountered a psychology master's thesis published online (by Edward Selby, M.Sc. 2007). Here's a link:
http://etd.lib.fsu.edu/theses/available/etd-07092007-164107/unrestricted/SelbyMastersThesisFinal.pdf
Selby makes the case well that negative emotional cascades leading to behavioural dyregulation are strongly fuelled by rumination. The events of behavioural dysregulation, such as self-injury, serve to distract one from the intense discomfort of rumination. Here is a quote from the conclusion:
"the findings of this study provide preliminary evidence for an
emotional cascade model of dysregulated behavior. In this model high levels of rumination may cause extremely intense states of negative affect, which result in dysregulated behaviors that distract from rumination and reduce that state of negative affect. This study specifically linked rumination to drinking to cope, binge-eating behaviors, reassurance seeking, and urgency, and it is likely that rumination is linked to a variety of other deregulated behaviors. "
Rumination, of course, is another phenomenon common to much "general dysfunction or misery." I am reminded how important it can be, as a practical therapeutic project with patients, to work on ways to move away from, or to let go of, rumination. (see my previous post on rumination: http://garthkroeker.blogspot.com/2011/08/chronic-pain-rumination.html)
Thursday, August 18, 2011
"Anti-psychiatry"
I'm just bumping up this post, originally from July 2008, because there have been some new comments.
There are a lot of strong opinions out there about psychiatry.
Some people are concerned that the practice of psychiatry has caused harm, perhaps by "over-medicalizing" issues that should be considered matters of personal challenge, character, individual choice & responsibility, spirituality, or normal human experience. Other concerns are that psychiatry is overly influenced by large pharmaceutical companies, whose agenda is to earn larger profits by selling more medication. Critics holding these concerns often consider the results of research studies to be biased, since they have often been sponsored by drug companies.
I think these concerns need to be heard and respected. There are specific examples about some of the concerns having some validity to them. In the history of psychiatry, as in the history of all other human endeavour, mistakes have been made. Small mistakes and large mistakes. On a systemic level, I think some of the core theories about psychiatry over the past hundred years have been laden with huge inaccuracies, despite the many nuggets of wisdom contained within them (Freud's ideas are one example). Many times, attempts at treatment have not helped, or perhaps have reduced a symptom at a very great expense to other aspects of the patient's life. There have been trends and fashions in treatment, such as the widespread use of anxiolytic drugs in past decades--while only later do we discover that these treatments can cause entrenched problems with addiction.
Conversely, there are some testimonial accounts of individuals who have had long histories of conventional psychiatric therapies, who have gone on to thrive once leaving all of these behind (perhaps pursuing alternative or naturopathic medicine, or making some other lifestyle change).
I think it is important to step back and examine the evidence closely, with a critical eye (in future posts I will refer to some of the evidence). I hold that there is a vast body of evidence about psychiatry to look at. And the evidence shows that the treatments are truly helpful. The evidence also shows that the treatments are not perfect, and that typically 30% of people do not have a good response from a given psychiatric treatment. The evidence also shows that up to 30% of patients respond to "placebo treatments". These facts lead to several criticisms about psychiatric treatment: first, there are many (perhaps in the first group of 30%) who have tried "conventional psychiatry" and have found that it hasn't worked for them. Second, there are those who have tried "non-psychiatric" treatments, and found that these HAVE worked for them (perhaps these people are in the 30% "placebo" group). Both of these groups may have a tendency to criticize psychiatry; yet there is another 40% -- a group whose ailments have resolved as a direct result of their psychiatric treatments.
This has always reminded me a bit of other areas of medicine, such as cardiology or oncology: the treatments in these specialties can be remarkably curative for some, only palliative for others, and may not work at all for others still.
I do agree that we must never "over-medicalize" any human ailment. It is rare for a problem to be truly cured by a pill. Usually, for any human concern or challenge, any therapy that helps has to be accompanied by holistic changes in lifestyle & behaviour. For the cardiac patient, this means rehabilitative exercise, healthy diet, no smoking, etc. For the mind, just as for the heart, there are many lifestyle habits that are healthy, restorative, and protective against recurrent illness.
Yet, very often people are too ill to be able to institute the "healthy lifestyle habits". The cardiac patient may require medication to control blood pressure and angina before being able to safely or comfortably exercise. Similarly, there are medical treatments in psychiatry that can hopefully provide enough symptom relief to allow the patient to energetically change their life for the better.
I have observed that the "anti-psychiatry" group can be very vocal. I could understand that the individuals among this group could have good reasons to hold such strong, forceful opinions. But I don't want this site to be a forum to spend a lot of time on this debate, I would rather focus on my own beliefs about ways to manage the mind's symptoms in the healthiest possible ways.
There are a lot of strong opinions out there about psychiatry.
Some people are concerned that the practice of psychiatry has caused harm, perhaps by "over-medicalizing" issues that should be considered matters of personal challenge, character, individual choice & responsibility, spirituality, or normal human experience. Other concerns are that psychiatry is overly influenced by large pharmaceutical companies, whose agenda is to earn larger profits by selling more medication. Critics holding these concerns often consider the results of research studies to be biased, since they have often been sponsored by drug companies.
I think these concerns need to be heard and respected. There are specific examples about some of the concerns having some validity to them. In the history of psychiatry, as in the history of all other human endeavour, mistakes have been made. Small mistakes and large mistakes. On a systemic level, I think some of the core theories about psychiatry over the past hundred years have been laden with huge inaccuracies, despite the many nuggets of wisdom contained within them (Freud's ideas are one example). Many times, attempts at treatment have not helped, or perhaps have reduced a symptom at a very great expense to other aspects of the patient's life. There have been trends and fashions in treatment, such as the widespread use of anxiolytic drugs in past decades--while only later do we discover that these treatments can cause entrenched problems with addiction.
Conversely, there are some testimonial accounts of individuals who have had long histories of conventional psychiatric therapies, who have gone on to thrive once leaving all of these behind (perhaps pursuing alternative or naturopathic medicine, or making some other lifestyle change).
I think it is important to step back and examine the evidence closely, with a critical eye (in future posts I will refer to some of the evidence). I hold that there is a vast body of evidence about psychiatry to look at. And the evidence shows that the treatments are truly helpful. The evidence also shows that the treatments are not perfect, and that typically 30% of people do not have a good response from a given psychiatric treatment. The evidence also shows that up to 30% of patients respond to "placebo treatments". These facts lead to several criticisms about psychiatric treatment: first, there are many (perhaps in the first group of 30%) who have tried "conventional psychiatry" and have found that it hasn't worked for them. Second, there are those who have tried "non-psychiatric" treatments, and found that these HAVE worked for them (perhaps these people are in the 30% "placebo" group). Both of these groups may have a tendency to criticize psychiatry; yet there is another 40% -- a group whose ailments have resolved as a direct result of their psychiatric treatments.
This has always reminded me a bit of other areas of medicine, such as cardiology or oncology: the treatments in these specialties can be remarkably curative for some, only palliative for others, and may not work at all for others still.
I do agree that we must never "over-medicalize" any human ailment. It is rare for a problem to be truly cured by a pill. Usually, for any human concern or challenge, any therapy that helps has to be accompanied by holistic changes in lifestyle & behaviour. For the cardiac patient, this means rehabilitative exercise, healthy diet, no smoking, etc. For the mind, just as for the heart, there are many lifestyle habits that are healthy, restorative, and protective against recurrent illness.
Yet, very often people are too ill to be able to institute the "healthy lifestyle habits". The cardiac patient may require medication to control blood pressure and angina before being able to safely or comfortably exercise. Similarly, there are medical treatments in psychiatry that can hopefully provide enough symptom relief to allow the patient to energetically change their life for the better.
I have observed that the "anti-psychiatry" group can be very vocal. I could understand that the individuals among this group could have good reasons to hold such strong, forceful opinions. But I don't want this site to be a forum to spend a lot of time on this debate, I would rather focus on my own beliefs about ways to manage the mind's symptoms in the healthiest possible ways.
Wednesday, August 10, 2011
Chronic Pain & Rumination
I was planning to write separate posts on chronic pain and on rumination; but I have found that these subjects are related to each other, so I thought I would combine them.
In this article, I am defining "rumination" as frequent, repetitive thoughts about symptoms or problems. Such recurrent thinking can consume so much time and energy, that little is left in the mind to permit quality of life. And the ruminations, while understandable in the context of troubling symptoms or problems, do not help to resolve the problems at all. Rumination can also refer to a gastrointestinal problem, which I am not discussing here.
Chronic physical pain obviously has a huge negative impact on quality of life. The presence of physical pain symptoms is a strong risk factor for suicide. (references: http://www.ncbi.nlm.nih.gov/pubmed/21668756 ; http://www.ncbi.nlm.nih.gov/pubmed/16420727 )
If physical pain and depression are combined, the severity of both problems is substantially elevated.
Treatment of chronic pain requires good comprehensive medical care. Investigation and treatment of underlying medical causes is obviously important. Coordinated involvement of a mutlidisciplinary team is ideal, though often lacking in many people's experience.
In the psychiatric realm, a variety of therapies can help:
1) mindfulness meditation. Jon Kabat-Zinn developed much of his work on mindfulness meditation with patients suffering from physical pain. In my opinion, meditation is extremely important, since it carries no risk, has a variety of possible and probable benefits, and is likely to help with both emotional and physical symptoms.
This study shows similar reductions in pain from a mindfulness program vs. a multidisciplinary pain program without a meditation focus:
http://www.ncbi.nlm.nih.gov/pubmed/21753729
This study shows improvements in various types of chronic pain conditions, with greater improvements in symptoms when subjects practiced more at home:
http://www.ncbi.nlm.nih.gov/pubmed/20004298
This study showed that mindfulness strategies probably work best for those who already have higher levels of mindfulness to begin with, as a type of character trait:
http://www.ncbi.nlm.nih.gov/pubmed/21254055
This study shows a slight advantage for a mindfulness meditation program to treat back pain:
http://www.ncbi.nlm.nih.gov/pubmed/17544212
An interesting study showing improvement in distressing intrusive thoughts and images following a meditation program. This shows that mindfulness exercises can substantially improve symptoms of rumination and even psychosis. In chronic pain, ruminations and intrusive thoughts about the pain itself are a very common feature, and an element of the vicious cycle of pain perpetuation and reduced quality of life. The study was of good quality, and the effect was quite substantial and robust:
http://www.ncbi.nlm.nih.gov/pubmed/19545481
Similarly, a study showing the mindfulness training specifically increases ability to "let go" (in this case, of OCD thoughts). "Letting go" of ruminations about pain is very helpful in managing chronic pain conditions:
http://www.ncbi.nlm.nih.gov/pubmed/18852623
Here's another study once again showing that mindfulness is specifically helpful to reduce rumination:
http://www.ncbi.nlm.nih.gov/pubmed/17291166
2) Cognitive-behavioural therapy
There is a significant research literature showing the effectiveness of CBT for managing pain conditions. Here are some research examples:
non-cardiac chest pain: http://www.ncbi.nlm.nih.gov/pubmed/21262413
chronic TMJ (jaw) pain: http://www.ncbi.nlm.nih.gov/pubmed/20655662
fibromyalgia: http://www.ncbi.nlm.nih.gov/pubmed/20521308
severe back pain: http://www.ncbi.nlm.nih.gov/pubmed/19967572
vulvodynia: http://www.ncbi.nlm.nih.gov/pubmed/19022580
back pain (here, active behavioural/physical therapy was necessary for optimal improvement in performance, as expected): http://www.ncbi.nlm.nih.gov/pubmed/16426449
chronic headaches: http://www.ncbi.nlm.nih.gov/pubmed/17690017
3) Medications
a) antidepressants:
Several antidepressant types could help with chronic pain: tricyclics such as amitriptyline have been used in this way for decades, with reasonable evidence-based support. Cymbalta (duloxetine) has been marketed for this, and is reasonable to try. However, venlafaxine (Effexor) is probably just as effective for pain symptoms.
There have been no studies comparing venlafaxine with duloxetine in pain patients; I suspect that there would be little difference. Currently, duloxetine is more expensive, so I do not believe it should be a first-line agent. SSRI antidepressants or bupropion appear not to be consistently helpful for treating physical pain.
Here`s an animal study showing a difference favoring a tricyclic over an SSRI or bupropion for pain management: http://www.ncbi.nlm.nih.gov/pubmed/20689938
Here`s a negative study on moclobemide for physical pain: http://www.ncbi.nlm.nih.gov/pubmed/7549169
This study shows equivalent benefits from amitriptyline and duloxetine, with over 50% of patients having good pain relief in diabetic neuropathy: http://www.ncbi.nlm.nih.gov/pubmed/21355098
This study shows benefits from duloxetine in fibromyalgia; again with over 50% of patients feeling much better, compared to about 30% with placebo: http://www.ncbi.nlm.nih.gov/pubmed/20843911
This study shows significant benefit in treating osteoarthritis pain with duloxetine; the pain relief was not related to any change in depression scores (which, in this population, were quite low and did not change very much with either duloxetine or placebo). I find this study quite significant, in that it is looking at a different variety of pain than most of the other research: http://www.ncbi.nlm.nih.gov/pubmed/19625125
This study shows relief attributable to duloxetine in depressed patients with idiopathic pain symptoms: http://www.ncbi.nlm.nih.gov/pubmed/18052564
Here, venlafaxine is shown to be an effective agent to prevent migraine headaches: http://www.ncbi.nlm.nih.gov/pubmed/15705120
Venlafaxine shown to be effective in treating functional chest pain:
http://www.ncbi.nlm.nih.gov/pubmed/20332772
A 2007 Cochrane review concluding that venlafaxine and tricyclics are effective for chronic pain:
http://www.ncbi.nlm.nih.gov/pubmed/17943857
b) anticonvulsants, e.g. gabapentin, pregabalin, carbamazapine, topiramate
A comparison of gabapentin, pregabalin, and amitriptyline in treating neuropathic cancer pain. All of these drugs clearly helped, with pregabalin probably the best. Aside from direct relief, these drugs resulted in lower doses of opiates being needed: http://www.ncbi.nlm.nih.gov/pubmed/21745832
A review of gabapentin treatment for neuropathic pain, affirming its usefulness, particularly at higher doses of 1800-3600 mg per day: http://www.ncbi.nlm.nih.gov/pubmed/12637113
This is a negative review article, showing that lamotrigine is unfortunately not likely to be useful in treating chronic pain: http://www.ncbi.nlm.nih.gov/pubmed/21328280
An interesting study showing that pregabalin can reduce postoperative morphine requirement acutely: http://www.ncbi.nlm.nih.gov/pubmed/21786524
This is an example, and a review article, part of the large literature showing that topiramate is an agent of choice to prevent or treat recurrent or chronic migraine. There is preliminary evidence at a case-report level that topiramate could help with other types of pain: http://www.ncbi.nlm.nih.gov/pubmed/19838625
c) opiates, such as codeine or morphine -- outside of the scope of this posting. These may have a role in managing non-malignant chronic pain, but supervision is needed from someone with experience prescribing opiates, a pain clinic, etc. Long-acting opiates such as methadone are being used more often in acute or chronic non-malignant pain conditions. Of course, there is a balance here between pain relief and addictive risk.
Here is a recent review, which basically affirms that the use of opiates for chronic non-cancer pain is an "iffy" practice, yet I do affirm that in some cases it may be necessary. In any case I think that experienced and specialized prescribers, such as those at a pain clinic, would be highly preferred:
http://www.ncbi.nlm.nih.gov/pubmed/21412367
d) Atypical opiate: tramadol. This is an interesting drug, for various reasons, including that it has antidepressant activity as well as being a physical analgesic. It is an opiate, but a significant portion of its analgesic properties come from non-opioid mechanisms, such as neurotransmitter reuptake inhibition. It does a potential for addictive problems, but the risk is clearly less than other opiates. For this reason, I think it is reasonable to think of using tramadol before using other opiates (such as codeine or morphine) in treating pain syndromes.
Chronic CNS effects of tramadol differ from those of morphine, supporting the evidence that tramadol has a smaller risk of inducing opiate dependence/addiction:
http://www.ncbi.nlm.nih.gov/pubmed/17401159
Tramadol can be identified subjectively as having opiate-like effects, but mainly at higher doses:
http://www.ncbi.nlm.nih.gov/pubmed/21467190
Here are animal studies using a mouse model of depression, suggesting effectiveness of tramadol.. However, I would want to see longer-term studies of this sort, as the acute beneficial action of any therapy does not necessarily prove that the benefits will last, in fact many acutely beneficial things can become harmful if used long-term (e.g. benzodiazepines):
http://www.ncbi.nlm.nih.gov/pubmed/9749830
http://www.ncbi.nlm.nih.gov/pubmed/12417248
An animal study suggesting that tramadol and anticonvulsants (in this case, specifically topiramate) can work synergestically (cooperatively) in relieving neuropathic pain: http://www.ncbi.nlm.nih.gov/pubmed/17532139
Treatment of refractory major depression with tramadol monotherapy: http://www.ncbi.nlm.nih.gov/pubmed/11305709
Rapid remission of ocd with tramadol:
http://www.ncbi.nlm.nih.gov/pubmed/10200754
http://www.ncbi.nlm.nih.gov/pubmed/9559288
Restless legs treatment with tramadol:
http://www.ncbi.nlm.nih.gov/pubmed/10221285
Treating catalepsy with tramadol:
http://www.ncbi.nlm.nih.gov/pubmed/14504345
Tramadol dependence : in general these articles show that tramadol dependence occurs, but is significantly less likely than with stronger opiates:
http://www.ncbi.nlm.nih.gov/pubmed/19827010
http://www.ncbi.nlm.nih.gov/pubmed/21467190
http://www.ncbi.nlm.nih.gov/pubmed/20589494
http://www.ncbi.nlm.nih.gov/pubmed/16716877
There is a risk of serotonin syndrome with tramadol, particularly if combined with other serotonergic drugs, such as SSRI antidepressants:
http://www.ncbi.nlm.nih.gov/pubmed/21147393
Other direct approaches to treat rumination:
Here is a study showing effectiveness using a modified form of cognitive therapy called competitive memory training. It basically involves teaching techniques to either accept, or become indifferent to, the themes of the rumination:
http://www.ncbi.nlm.nih.gov/pubmed/21784413
Here`s a similar recent study showing improved relief in chronic depression with a CBT style modified to target rumination:
http://www.ncbi.nlm.nih.gov/pubmed/21778171
An interesting study from the psychology literature which shows that rumination is associated with a type of cognitive deficit involving reduced ability to manage negative material in working memory. This suggests to me that cognitive exercises, ones which train working memory, could have a role in treating depression and rumination. Conversely, it suggests to me that practicing ways of "letting go" such as via CBT or meditation, could improve working memory (by freeing working memory space of irrelevant, ruminative, or intrusive negative material), and therefore improve intellectual functioning, academic performance, etc. http://www.ncbi.nlm.nih.gov/pubmed/21742932
Here's one of many articles discussing rumination as a risk factor for depressive relapse or chronicity. Clearly, tactics to help manage or prevent rumination are very important in both acute treatment and in prevention:
http://www.ncbi.nlm.nih.gov/pubmed/19899844
Another article discussing the role of rumination as a sort of emotional amplifier, which causes "impaired down-regulation of negative feelings" -- thus preventing the maintenance of positivity or relationship health after a stressor. Such a dynamic would be a recipe for life disappointments to consistently derail one's emotional life. Once again, practicing ways to manage rumination directly could therefore help with emotional resilience, and prevent a recurrent depressive cycle:
http://www.ncbi.nlm.nih.gov/pubmed/21432690
In summary, there are a variety of ways to treat or manage chronic pain and rumination. Rumination itself may be an important perpetuating factor in pain syndromes. Due to the presence of many symptoms in such syndromes, affecting both physical and emotional domains, it is important to have a cohesive, integrated treatment plan. There is a risk of having multiple sources of therapy, each of which targeting only part of the symptom complex, which potentially could complicate or confound efficient treatment efforts. In physical pain, emotional pain, or rumination, it can be extremely valuable to practice ways of "letting go."
In this article, I am defining "rumination" as frequent, repetitive thoughts about symptoms or problems. Such recurrent thinking can consume so much time and energy, that little is left in the mind to permit quality of life. And the ruminations, while understandable in the context of troubling symptoms or problems, do not help to resolve the problems at all. Rumination can also refer to a gastrointestinal problem, which I am not discussing here.
Chronic physical pain obviously has a huge negative impact on quality of life. The presence of physical pain symptoms is a strong risk factor for suicide. (references: http://www.ncbi.nlm.nih.gov/pubmed/21668756 ; http://www.ncbi.nlm.nih.gov/pubmed/16420727 )
If physical pain and depression are combined, the severity of both problems is substantially elevated.
Treatment of chronic pain requires good comprehensive medical care. Investigation and treatment of underlying medical causes is obviously important. Coordinated involvement of a mutlidisciplinary team is ideal, though often lacking in many people's experience.
In the psychiatric realm, a variety of therapies can help:
1) mindfulness meditation. Jon Kabat-Zinn developed much of his work on mindfulness meditation with patients suffering from physical pain. In my opinion, meditation is extremely important, since it carries no risk, has a variety of possible and probable benefits, and is likely to help with both emotional and physical symptoms.
This study shows similar reductions in pain from a mindfulness program vs. a multidisciplinary pain program without a meditation focus:
http://www.ncbi.nlm.nih.gov/pubmed/21753729
This study shows improvements in various types of chronic pain conditions, with greater improvements in symptoms when subjects practiced more at home:
http://www.ncbi.nlm.nih.gov/pubmed/20004298
This study showed that mindfulness strategies probably work best for those who already have higher levels of mindfulness to begin with, as a type of character trait:
http://www.ncbi.nlm.nih.gov/pubmed/21254055
This study shows a slight advantage for a mindfulness meditation program to treat back pain:
http://www.ncbi.nlm.nih.gov/pubmed/17544212
An interesting study showing improvement in distressing intrusive thoughts and images following a meditation program. This shows that mindfulness exercises can substantially improve symptoms of rumination and even psychosis. In chronic pain, ruminations and intrusive thoughts about the pain itself are a very common feature, and an element of the vicious cycle of pain perpetuation and reduced quality of life. The study was of good quality, and the effect was quite substantial and robust:
http://www.ncbi.nlm.nih.gov/pubmed/19545481
Similarly, a study showing the mindfulness training specifically increases ability to "let go" (in this case, of OCD thoughts). "Letting go" of ruminations about pain is very helpful in managing chronic pain conditions:
http://www.ncbi.nlm.nih.gov/pubmed/18852623
Here's another study once again showing that mindfulness is specifically helpful to reduce rumination:
http://www.ncbi.nlm.nih.gov/pubmed/17291166
2) Cognitive-behavioural therapy
There is a significant research literature showing the effectiveness of CBT for managing pain conditions. Here are some research examples:
non-cardiac chest pain: http://www.ncbi.nlm.nih.gov/pubmed/21262413
chronic TMJ (jaw) pain: http://www.ncbi.nlm.nih.gov/pubmed/20655662
fibromyalgia: http://www.ncbi.nlm.nih.gov/pubmed/20521308
severe back pain: http://www.ncbi.nlm.nih.gov/pubmed/19967572
vulvodynia: http://www.ncbi.nlm.nih.gov/pubmed/19022580
back pain (here, active behavioural/physical therapy was necessary for optimal improvement in performance, as expected): http://www.ncbi.nlm.nih.gov/pubmed/16426449
chronic headaches: http://www.ncbi.nlm.nih.gov/pubmed/17690017
3) Medications
a) antidepressants:
Several antidepressant types could help with chronic pain: tricyclics such as amitriptyline have been used in this way for decades, with reasonable evidence-based support. Cymbalta (duloxetine) has been marketed for this, and is reasonable to try. However, venlafaxine (Effexor) is probably just as effective for pain symptoms.
There have been no studies comparing venlafaxine with duloxetine in pain patients; I suspect that there would be little difference. Currently, duloxetine is more expensive, so I do not believe it should be a first-line agent. SSRI antidepressants or bupropion appear not to be consistently helpful for treating physical pain.
Here`s an animal study showing a difference favoring a tricyclic over an SSRI or bupropion for pain management: http://www.ncbi.nlm.nih.gov/pubmed/20689938
Here`s a negative study on moclobemide for physical pain: http://www.ncbi.nlm.nih.gov/pubmed/7549169
This study shows equivalent benefits from amitriptyline and duloxetine, with over 50% of patients having good pain relief in diabetic neuropathy: http://www.ncbi.nlm.nih.gov/pubmed/21355098
This study shows benefits from duloxetine in fibromyalgia; again with over 50% of patients feeling much better, compared to about 30% with placebo: http://www.ncbi.nlm.nih.gov/pubmed/20843911
This study shows significant benefit in treating osteoarthritis pain with duloxetine; the pain relief was not related to any change in depression scores (which, in this population, were quite low and did not change very much with either duloxetine or placebo). I find this study quite significant, in that it is looking at a different variety of pain than most of the other research: http://www.ncbi.nlm.nih.gov/pubmed/19625125
This study shows relief attributable to duloxetine in depressed patients with idiopathic pain symptoms: http://www.ncbi.nlm.nih.gov/pubmed/18052564
Here, venlafaxine is shown to be an effective agent to prevent migraine headaches: http://www.ncbi.nlm.nih.gov/pubmed/15705120
Venlafaxine shown to be effective in treating functional chest pain:
http://www.ncbi.nlm.nih.gov/pubmed/20332772
A 2007 Cochrane review concluding that venlafaxine and tricyclics are effective for chronic pain:
http://www.ncbi.nlm.nih.gov/pubmed/17943857
b) anticonvulsants, e.g. gabapentin, pregabalin, carbamazapine, topiramate
A comparison of gabapentin, pregabalin, and amitriptyline in treating neuropathic cancer pain. All of these drugs clearly helped, with pregabalin probably the best. Aside from direct relief, these drugs resulted in lower doses of opiates being needed: http://www.ncbi.nlm.nih.gov/pubmed/21745832
A review of gabapentin treatment for neuropathic pain, affirming its usefulness, particularly at higher doses of 1800-3600 mg per day: http://www.ncbi.nlm.nih.gov/pubmed/12637113
This is a negative review article, showing that lamotrigine is unfortunately not likely to be useful in treating chronic pain: http://www.ncbi.nlm.nih.gov/pubmed/21328280
An interesting study showing that pregabalin can reduce postoperative morphine requirement acutely: http://www.ncbi.nlm.nih.gov/pubmed/21786524
This is an example, and a review article, part of the large literature showing that topiramate is an agent of choice to prevent or treat recurrent or chronic migraine. There is preliminary evidence at a case-report level that topiramate could help with other types of pain: http://www.ncbi.nlm.nih.gov/pubmed/19838625
c) opiates, such as codeine or morphine -- outside of the scope of this posting. These may have a role in managing non-malignant chronic pain, but supervision is needed from someone with experience prescribing opiates, a pain clinic, etc. Long-acting opiates such as methadone are being used more often in acute or chronic non-malignant pain conditions. Of course, there is a balance here between pain relief and addictive risk.
Here is a recent review, which basically affirms that the use of opiates for chronic non-cancer pain is an "iffy" practice, yet I do affirm that in some cases it may be necessary. In any case I think that experienced and specialized prescribers, such as those at a pain clinic, would be highly preferred:
http://www.ncbi.nlm.nih.gov/pubmed/21412367
d) Atypical opiate: tramadol. This is an interesting drug, for various reasons, including that it has antidepressant activity as well as being a physical analgesic. It is an opiate, but a significant portion of its analgesic properties come from non-opioid mechanisms, such as neurotransmitter reuptake inhibition. It does a potential for addictive problems, but the risk is clearly less than other opiates. For this reason, I think it is reasonable to think of using tramadol before using other opiates (such as codeine or morphine) in treating pain syndromes.
Chronic CNS effects of tramadol differ from those of morphine, supporting the evidence that tramadol has a smaller risk of inducing opiate dependence/addiction:
http://www.ncbi.nlm.nih.gov/pubmed/17401159
Tramadol can be identified subjectively as having opiate-like effects, but mainly at higher doses:
http://www.ncbi.nlm.nih.gov/pubmed/21467190
Here are animal studies using a mouse model of depression, suggesting effectiveness of tramadol.. However, I would want to see longer-term studies of this sort, as the acute beneficial action of any therapy does not necessarily prove that the benefits will last, in fact many acutely beneficial things can become harmful if used long-term (e.g. benzodiazepines):
http://www.ncbi.nlm.nih.gov/pubmed/9749830
http://www.ncbi.nlm.nih.gov/pubmed/12417248
An animal study suggesting that tramadol and anticonvulsants (in this case, specifically topiramate) can work synergestically (cooperatively) in relieving neuropathic pain: http://www.ncbi.nlm.nih.gov/pubmed/17532139
Treatment of refractory major depression with tramadol monotherapy: http://www.ncbi.nlm.nih.gov/pubmed/11305709
Rapid remission of ocd with tramadol:
http://www.ncbi.nlm.nih.gov/pubmed/10200754
http://www.ncbi.nlm.nih.gov/pubmed/9559288
Restless legs treatment with tramadol:
http://www.ncbi.nlm.nih.gov/pubmed/10221285
Treating catalepsy with tramadol:
http://www.ncbi.nlm.nih.gov/pubmed/14504345
Tramadol dependence : in general these articles show that tramadol dependence occurs, but is significantly less likely than with stronger opiates:
http://www.ncbi.nlm.nih.gov/pubmed/19827010
http://www.ncbi.nlm.nih.gov/pubmed/21467190
http://www.ncbi.nlm.nih.gov/pubmed/20589494
http://www.ncbi.nlm.nih.gov/pubmed/16716877
There is a risk of serotonin syndrome with tramadol, particularly if combined with other serotonergic drugs, such as SSRI antidepressants:
http://www.ncbi.nlm.nih.gov/pubmed/21147393
Other direct approaches to treat rumination:
Here is a study showing effectiveness using a modified form of cognitive therapy called competitive memory training. It basically involves teaching techniques to either accept, or become indifferent to, the themes of the rumination:
http://www.ncbi.nlm.nih.gov/pubmed/21784413
Here`s a similar recent study showing improved relief in chronic depression with a CBT style modified to target rumination:
http://www.ncbi.nlm.nih.gov/pubmed/21778171
An interesting study from the psychology literature which shows that rumination is associated with a type of cognitive deficit involving reduced ability to manage negative material in working memory. This suggests to me that cognitive exercises, ones which train working memory, could have a role in treating depression and rumination. Conversely, it suggests to me that practicing ways of "letting go" such as via CBT or meditation, could improve working memory (by freeing working memory space of irrelevant, ruminative, or intrusive negative material), and therefore improve intellectual functioning, academic performance, etc. http://www.ncbi.nlm.nih.gov/pubmed/21742932
Here's one of many articles discussing rumination as a risk factor for depressive relapse or chronicity. Clearly, tactics to help manage or prevent rumination are very important in both acute treatment and in prevention:
http://www.ncbi.nlm.nih.gov/pubmed/19899844
Another article discussing the role of rumination as a sort of emotional amplifier, which causes "impaired down-regulation of negative feelings" -- thus preventing the maintenance of positivity or relationship health after a stressor. Such a dynamic would be a recipe for life disappointments to consistently derail one's emotional life. Once again, practicing ways to manage rumination directly could therefore help with emotional resilience, and prevent a recurrent depressive cycle:
http://www.ncbi.nlm.nih.gov/pubmed/21432690
In summary, there are a variety of ways to treat or manage chronic pain and rumination. Rumination itself may be an important perpetuating factor in pain syndromes. Due to the presence of many symptoms in such syndromes, affecting both physical and emotional domains, it is important to have a cohesive, integrated treatment plan. There is a risk of having multiple sources of therapy, each of which targeting only part of the symptom complex, which potentially could complicate or confound efficient treatment efforts. In physical pain, emotional pain, or rumination, it can be extremely valuable to practice ways of "letting go."
Wednesday, July 27, 2011
Optimal Sleep Duration
The best study which examines the relationship between sleep duration and mortality risk was published in 2007 by Hublin et al in the journal Sleep. Here's a link to the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/17969458
It is part of the Finnish twin study, which followed over 20 000 twins over a 22 year period. This is an extremely large cohort, and the study had very high response rates. The analysis was thoughtful and comprehensive.
They showed that mortality rates were lowest for those who sleep between 7 and 8 hours per day. For those sleeping less than 7 hours per day, or more than 8, the mortality rates were about 20-25% higher. The results were adjusted for the covariates of education, marital status, age, working status, BMI, social class, drinking behavior, physical activity, smoking, and life satisfaction. Interestingly, and unexpectedly, sleep quality was not shown to be associated with differences in mortality risk.
The argument could be made that average sleep duration has a non-causal association with lower mortality. That is, people who happen to be healthier in the first place are more likely to have average sleep length. But another part of this analysis suggests that this is more than a non-causal association: subjects who changed their sleep duration during the course of this 22 year follow-up also changed their mortality rate, after controlling for the measured confounding factors. I suppose it could still be true that some other mortality-increasing factor was the cause of the sleep duration change, and not the other way around.
In conclusion, this data supports the commonly held belief that 7-8 hours of sleep per night is a desirable goal. It may be that particular individuals have a different "set point" for optimal sleep, and for those individuals optimal health might result from more or less hours than this average. Yet I do not actually see firm evidence of this in the research I've seen.
A 2010 meta-analysis supports the same conclusion: http://www.ncbi.nlm.nih.gov/pubmed/20469800 but I think the authors understate their findings. In particular, while a lot of the data showing increased mortality in short sleepers defined short sleep to be under 7 hours, the authors state in their discussion that "consistently sleeping 6 to 8 h per night may therefore be optimal for health." I think there is a significant difference between 6 and 7 hours, particularly due to pressures in the culture where many people are sleeping only 6 hours because of a busy schedule, while really needing 7 or 8.
Knutson in 2007 published a good article showing that sleep deprivation causes impairments in glucose tolerance (similar to the changes which occur in the development of type II diabetes), and impairments in the hormones associated with appetite regulation: http://www.ncbi.nlm.nih.gov/pubmed/185162
Here's one of the articles in the literature showing that sleep deprivation leads to an increase in proinflammatory cytokines and abnormal immune activation: http://www.ncbi.nlm.nih.gov/pubmed/19240794
I think it is especially true that if one has signs or symptoms related to sleep duration (e.g. feeling sleepy in the daytime after sleeping only 6 hours per night) then this could be taken as strong evidence that sleep duration should be increased up to the average (7-8 hours), if circumstances permit.
Patterns of sleeping long hours (above average) could be approached similarly, but of course if the reason for the long sleeping duration is medical illness or medication effects, etc. it would not be healthy to force oneself into a shorter (average) sleep regimen.
http://www.ncbi.nlm.nih.gov/pubmed/17969458
It is part of the Finnish twin study, which followed over 20 000 twins over a 22 year period. This is an extremely large cohort, and the study had very high response rates. The analysis was thoughtful and comprehensive.
They showed that mortality rates were lowest for those who sleep between 7 and 8 hours per day. For those sleeping less than 7 hours per day, or more than 8, the mortality rates were about 20-25% higher. The results were adjusted for the covariates of education, marital status, age, working status, BMI, social class, drinking behavior, physical activity, smoking, and life satisfaction. Interestingly, and unexpectedly, sleep quality was not shown to be associated with differences in mortality risk.
The argument could be made that average sleep duration has a non-causal association with lower mortality. That is, people who happen to be healthier in the first place are more likely to have average sleep length. But another part of this analysis suggests that this is more than a non-causal association: subjects who changed their sleep duration during the course of this 22 year follow-up also changed their mortality rate, after controlling for the measured confounding factors. I suppose it could still be true that some other mortality-increasing factor was the cause of the sleep duration change, and not the other way around.
In conclusion, this data supports the commonly held belief that 7-8 hours of sleep per night is a desirable goal. It may be that particular individuals have a different "set point" for optimal sleep, and for those individuals optimal health might result from more or less hours than this average. Yet I do not actually see firm evidence of this in the research I've seen.
A 2010 meta-analysis supports the same conclusion: http://www.ncbi.nlm.nih.gov/pubmed/20469800 but I think the authors understate their findings. In particular, while a lot of the data showing increased mortality in short sleepers defined short sleep to be under 7 hours, the authors state in their discussion that "consistently sleeping 6 to 8 h per night may therefore be optimal for health." I think there is a significant difference between 6 and 7 hours, particularly due to pressures in the culture where many people are sleeping only 6 hours because of a busy schedule, while really needing 7 or 8.
Knutson in 2007 published a good article showing that sleep deprivation causes impairments in glucose tolerance (similar to the changes which occur in the development of type II diabetes), and impairments in the hormones associated with appetite regulation: http://www.ncbi.nlm.nih.gov/pubmed/185162
Here's one of the articles in the literature showing that sleep deprivation leads to an increase in proinflammatory cytokines and abnormal immune activation: http://www.ncbi.nlm.nih.gov/pubmed/19240794
I think it is especially true that if one has signs or symptoms related to sleep duration (e.g. feeling sleepy in the daytime after sleeping only 6 hours per night) then this could be taken as strong evidence that sleep duration should be increased up to the average (7-8 hours), if circumstances permit.
Patterns of sleeping long hours (above average) could be approached similarly, but of course if the reason for the long sleeping duration is medical illness or medication effects, etc. it would not be healthy to force oneself into a shorter (average) sleep regimen.
Subscribe to:
Posts (Atom)