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.
Thursday, August 18, 2011
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.
Monday, June 27, 2011
Somatoform Disorders & CFS : a discussion
Somatoform disorders could be considered clusters or syndromes of physical symptoms which have a psychological cause.
Here are some examples:
1) somatization disorder -- a syndrome of multiple physical symptoms--typically pain symptoms-- which have a psychological cause
2) conversion disorder -- typically there is a complaint of paralysis or loss of sensation (including blindness) despite an absence of neurological signs; the symptoms may be generated without conscious intent, but may be profoundly disabling. With modern examination techniques and tests, these symptoms are easily demonstrated to be of non-neurological origin.
3) somatic delusions, in the context of psychotic depression or schizophreniform disorders. These have a wide variety of manifestations, though are most commonly bizarre in nature. Arguably, cases of somatization or conversion could be treated as somatic delusions.
4) somatic manifestations of anxiety -- this is extremely familiar to us all: tremor, sweating, bowel problems, etc. can all occur as a direct obvious consequence of anxiety. At times this physical component becomes the dominant feature, leading to behaviours intended to relieve the physical complaint, leading in turn to worsened avoidance, withdrawal, and exacerbation of the underlying problem.
This whole subject requires a lot of care, in my opinion. I believe that somatization is very common, and exists in a wide range of extremity--from minor symptoms to syndromes that can be almost totally disabling--yet it is also true that undiagnosed medical ailments of non-psychological origin can often be misdiagnosed as psychosomatic or somatoform. Therefore, thorough physical medical assessment and care is needed as a multidisciplinary strategy to manage these problems. These types of problems do indeed tend to be handled poorly by the conventional medical system--either through excessive and harmful medical interventions (e.g. in Munchausen's Syndrome), or through the dismissive neglect of a frustrated caregiver.
I think it is fair to say--and an observation I certainly find consistently in my experience--that physical symptoms of any cause ALWAYS have a psychological component as well. Often times, the psychological component is simple and direct: recurrent migraine headaches, malignant chronic pain, recurrent seizures, etc. (among hundreds of different causes of physical symptoms) cause a disruption to daily life & function, and their unpredictable patterns can leave one in a nearly constant state of anxiety. It can be hard to plan activities, time for relationships, work schedules, etc. when symptoms may come at any moment. So there is obvious direct psychological stress. This stress understandably can cause a feedback loop which may exacerbate the underlying medical condition.
Other times, I believe that the psychological effects of medical conditions can be more subtle or indirect. Chronic conditions can come to have a lot of power to redefine one's sense of self, often in a way which pronounces one to be more disabled than the medical problems necessitate. Some types of symptom clusters may be sufficiently common as to allow a community of fellow sufferers to form. While this may permit the supportive care of a community, it may also consolidate or entrench the aspects of the phenomenon which have to do with identity. The relief that one may find in a group of people experiencing something similar may sometimes be so compelling that entrenched factitious beliefs about disability are deepened, at the expense of therapeutic growth.
Some currently unexplained diagnostic entities, such as chronic fatigue syndrome (CFS), may in some cases be examples of complex somatoform illness. I acknowledge that in other cases--perhaps even in the majority--there may well be some as yet unexplained physical pathology driving the symptoms. A physiologic disposition towards fatigue may cause a cascade of behavioural changes (including withdrawal from activities), leading to a further cascade of cognitions about illness, mood change (which can often present itself, for many people, in a further somatized set of symptoms), and perpetuating of underlying symptoms. The worldwide network of fellow sufferers may lead to perpetuation of symptoms, rather than relief, because the group consolidates some of the beliefs and identity formation which individuals may have about the condition, and also may agitate against what is seen as a dismissive or ineffectual medical system. The group dynamics may also foster the spread of various spurious alternative therapies, whose evidence base would often consist of glowing testimonial accounts rather than careful randomized data. Factitious therapies could sometimes be quite effective for factitious illnesses, since the therapeutic effort would permit the sufferer a psychological opportunity to move away from the illness symptoms, and attribute the improvement to something external, rather than to psychological change. Such is, in my opinion, the basis for most stories of so-called "faith healing" which have been around for millenia.
It is helpful to have observed extreme examples of somatoform illness. Case examples include individuals who have had recurrent factitious seizures (pseudoseizures), often leading to dangerous and harmfully inappropriate medical interventions. Many persons with a history of pseudoseizures also have neurologically-based epilepsy as well: somatized, factitious, or conversion symptoms often co-exist with their non-psychiatric counterparts. Other case examples include situations where individuals are delusionally convinced that they are paralyzed (due to a conversion disorder) causing them to have lived in a wheelchair for years. Such individuals often have networks of people in their lives who support them in their paralyzed role; such supporters often include physicians and other caregivers. Yet, it has been an amazing experience for me to witness cases of this type--cases where there has never been any objective sign of neurologic disease, but where the impact of the problem has been extreme; if a very careful neuropsychiatric evaluation is done, with strongly structured psychiatric and rehabilitative therapy, I have seen situations where a person experiencing paralysis is able to walk home after a hospital stay.
But cases like these are inevitably complex. If a person has lived in a certain way for years, the behaviours themselves, and the associated thoughts, become integrated into identity. If you live as a paralyzed person for many years, it will not be so easy to get up and walk, even if you are neurologically healthy. There are physical barriers, but obvious psychological and social ones as well.
I believe this is a theme which epitomizes our understanding of brain function: repeated behaviour entrenches neural pathways. If "illness behaviour" exists despite "no illness", the brain learns to function "as if" a physical injury were present. It is just like language learning--with immersive experience over a course of months or years, the brain will speak the new language with ever greater fluency. It is a difficult task for the brain to "unlearn" such experience.
But this suggests a therapeutic imperative: for all cases of this type, immersive physical rehabilitation is necessary. In every single case I have ever seen of severe conversion, for example, the cure required intensive, prolonged, structured involvement of physiotherapists, in addition to whatever medications (typically antidepressants and antipsychotics) and psychotherapeutic work the person needed.
I believe this theme crosses over into the realm of ALL chronic disease, regardless of cause. Management of chronic disability or chronic diseases is greatly assisted by physical rehabilitation. In the language of narrative therapy, if we consider the illness or symptom to be like a negative character in our lives, that character is constantly telling us to do less and less--part of the therapy to challenge this is to find a structured and safe manner in which to do more and more, or to optimize our fitness so that we can do the most despite the limitations imposed by the disease.
Another interesting modality of therapy for conversion, one which can illustrate very compellingly the existence of a structure of drives and defenses first suggested by Freud, is the so-called "amytal interview." In the version I have seen, a patient with a conversion syndrome (following informed consent, of course) is given a dose of ritalin (which allows more amytal to be given without loss of consciousness), followed by intravenous sodium amytal (a barbiturate), with the supervision of an anesthetist in a well-equipped medical setting. The dose is titrated just to the point before the patient loses consciousness. The effect of the medication is to cause disinhibition. In this condition, the psychological forces necessary to continue the conversion symptom are weakened, so for example a person describing paralysis of an arm can be guided to raise the paralyzed arm in the air, and flex it, etc. This event can be videotaped. When the effects of the drug wear off, the person may not remember the scene, but when presented with the video footage (of the non-paralyzed limb in action), the person's psychological defense of conversion will be substantially weakened. As a result, often times a strong emotional reaction takes place, usually the overt emotions or affects consistent with a severe underlying depression which had previously shown itself through "paralysis." In this way, "conversion" operates as a psychological defense, a way in which the brain deals emotionally or behaviourally with a painful symptom. These defenses can be vital ways to survive in the world, but sometimes--as in conversion disorders--the defense system goes awry, and becomes the core problem.
Here are some examples:
1) somatization disorder -- a syndrome of multiple physical symptoms--typically pain symptoms-- which have a psychological cause
2) conversion disorder -- typically there is a complaint of paralysis or loss of sensation (including blindness) despite an absence of neurological signs; the symptoms may be generated without conscious intent, but may be profoundly disabling. With modern examination techniques and tests, these symptoms are easily demonstrated to be of non-neurological origin.
3) somatic delusions, in the context of psychotic depression or schizophreniform disorders. These have a wide variety of manifestations, though are most commonly bizarre in nature. Arguably, cases of somatization or conversion could be treated as somatic delusions.
4) somatic manifestations of anxiety -- this is extremely familiar to us all: tremor, sweating, bowel problems, etc. can all occur as a direct obvious consequence of anxiety. At times this physical component becomes the dominant feature, leading to behaviours intended to relieve the physical complaint, leading in turn to worsened avoidance, withdrawal, and exacerbation of the underlying problem.
This whole subject requires a lot of care, in my opinion. I believe that somatization is very common, and exists in a wide range of extremity--from minor symptoms to syndromes that can be almost totally disabling--yet it is also true that undiagnosed medical ailments of non-psychological origin can often be misdiagnosed as psychosomatic or somatoform. Therefore, thorough physical medical assessment and care is needed as a multidisciplinary strategy to manage these problems. These types of problems do indeed tend to be handled poorly by the conventional medical system--either through excessive and harmful medical interventions (e.g. in Munchausen's Syndrome), or through the dismissive neglect of a frustrated caregiver.
I think it is fair to say--and an observation I certainly find consistently in my experience--that physical symptoms of any cause ALWAYS have a psychological component as well. Often times, the psychological component is simple and direct: recurrent migraine headaches, malignant chronic pain, recurrent seizures, etc. (among hundreds of different causes of physical symptoms) cause a disruption to daily life & function, and their unpredictable patterns can leave one in a nearly constant state of anxiety. It can be hard to plan activities, time for relationships, work schedules, etc. when symptoms may come at any moment. So there is obvious direct psychological stress. This stress understandably can cause a feedback loop which may exacerbate the underlying medical condition.
Other times, I believe that the psychological effects of medical conditions can be more subtle or indirect. Chronic conditions can come to have a lot of power to redefine one's sense of self, often in a way which pronounces one to be more disabled than the medical problems necessitate. Some types of symptom clusters may be sufficiently common as to allow a community of fellow sufferers to form. While this may permit the supportive care of a community, it may also consolidate or entrench the aspects of the phenomenon which have to do with identity. The relief that one may find in a group of people experiencing something similar may sometimes be so compelling that entrenched factitious beliefs about disability are deepened, at the expense of therapeutic growth.
Some currently unexplained diagnostic entities, such as chronic fatigue syndrome (CFS), may in some cases be examples of complex somatoform illness. I acknowledge that in other cases--perhaps even in the majority--there may well be some as yet unexplained physical pathology driving the symptoms. A physiologic disposition towards fatigue may cause a cascade of behavioural changes (including withdrawal from activities), leading to a further cascade of cognitions about illness, mood change (which can often present itself, for many people, in a further somatized set of symptoms), and perpetuating of underlying symptoms. The worldwide network of fellow sufferers may lead to perpetuation of symptoms, rather than relief, because the group consolidates some of the beliefs and identity formation which individuals may have about the condition, and also may agitate against what is seen as a dismissive or ineffectual medical system. The group dynamics may also foster the spread of various spurious alternative therapies, whose evidence base would often consist of glowing testimonial accounts rather than careful randomized data. Factitious therapies could sometimes be quite effective for factitious illnesses, since the therapeutic effort would permit the sufferer a psychological opportunity to move away from the illness symptoms, and attribute the improvement to something external, rather than to psychological change. Such is, in my opinion, the basis for most stories of so-called "faith healing" which have been around for millenia.
It is helpful to have observed extreme examples of somatoform illness. Case examples include individuals who have had recurrent factitious seizures (pseudoseizures), often leading to dangerous and harmfully inappropriate medical interventions. Many persons with a history of pseudoseizures also have neurologically-based epilepsy as well: somatized, factitious, or conversion symptoms often co-exist with their non-psychiatric counterparts. Other case examples include situations where individuals are delusionally convinced that they are paralyzed (due to a conversion disorder) causing them to have lived in a wheelchair for years. Such individuals often have networks of people in their lives who support them in their paralyzed role; such supporters often include physicians and other caregivers. Yet, it has been an amazing experience for me to witness cases of this type--cases where there has never been any objective sign of neurologic disease, but where the impact of the problem has been extreme; if a very careful neuropsychiatric evaluation is done, with strongly structured psychiatric and rehabilitative therapy, I have seen situations where a person experiencing paralysis is able to walk home after a hospital stay.
But cases like these are inevitably complex. If a person has lived in a certain way for years, the behaviours themselves, and the associated thoughts, become integrated into identity. If you live as a paralyzed person for many years, it will not be so easy to get up and walk, even if you are neurologically healthy. There are physical barriers, but obvious psychological and social ones as well.
I believe this is a theme which epitomizes our understanding of brain function: repeated behaviour entrenches neural pathways. If "illness behaviour" exists despite "no illness", the brain learns to function "as if" a physical injury were present. It is just like language learning--with immersive experience over a course of months or years, the brain will speak the new language with ever greater fluency. It is a difficult task for the brain to "unlearn" such experience.
But this suggests a therapeutic imperative: for all cases of this type, immersive physical rehabilitation is necessary. In every single case I have ever seen of severe conversion, for example, the cure required intensive, prolonged, structured involvement of physiotherapists, in addition to whatever medications (typically antidepressants and antipsychotics) and psychotherapeutic work the person needed.
I believe this theme crosses over into the realm of ALL chronic disease, regardless of cause. Management of chronic disability or chronic diseases is greatly assisted by physical rehabilitation. In the language of narrative therapy, if we consider the illness or symptom to be like a negative character in our lives, that character is constantly telling us to do less and less--part of the therapy to challenge this is to find a structured and safe manner in which to do more and more, or to optimize our fitness so that we can do the most despite the limitations imposed by the disease.
Another interesting modality of therapy for conversion, one which can illustrate very compellingly the existence of a structure of drives and defenses first suggested by Freud, is the so-called "amytal interview." In the version I have seen, a patient with a conversion syndrome (following informed consent, of course) is given a dose of ritalin (which allows more amytal to be given without loss of consciousness), followed by intravenous sodium amytal (a barbiturate), with the supervision of an anesthetist in a well-equipped medical setting. The dose is titrated just to the point before the patient loses consciousness. The effect of the medication is to cause disinhibition. In this condition, the psychological forces necessary to continue the conversion symptom are weakened, so for example a person describing paralysis of an arm can be guided to raise the paralyzed arm in the air, and flex it, etc. This event can be videotaped. When the effects of the drug wear off, the person may not remember the scene, but when presented with the video footage (of the non-paralyzed limb in action), the person's psychological defense of conversion will be substantially weakened. As a result, often times a strong emotional reaction takes place, usually the overt emotions or affects consistent with a severe underlying depression which had previously shown itself through "paralysis." In this way, "conversion" operates as a psychological defense, a way in which the brain deals emotionally or behaviourally with a painful symptom. These defenses can be vital ways to survive in the world, but sometimes--as in conversion disorders--the defense system goes awry, and becomes the core problem.
A negative study on vitamin d supplementation
http://www.ncbi.nlm.nih.gov/pubmed/21525520
this 2011 randomized, controlled, prospective study from the British Journal of Psychiatry shows that vitamin d supplementation did not improve well-being in a group of over 1000 elderly women compared to a similar-sized control group.
This is a good study, with negative results. I don't think it means that vitamin d is of no use, but rather that it cannot be assumed to have obvious positive effects for everyone. Some of the effects measured in other vitamin d studies may be the result of non-causative associations (e.g. those with various healthier habits and health paramaters may be more likely to have higher vitamin d levels, but the vitamin d is not the cause of this healthiness, it results from it)
However, the data on this issue continues to evolve. There is some good positive data on vitamin d as well, though not enough in terms of randomized, prospective studies. It will be important, for example, to look at whether vitamin d could obviously be an effective adjunct to other therapies for treating depression. Or whether vitamin d alone has little effect, unless combined with other positive factors.
Meanwhile, I still believe that the standard recommended daily dose of 400 IU for vitamin D is too low, and that 1000-2000 IU per day is better.
See my previous post on vitamin d, http://garthkroeker.blogspot.com/2009/02/vitamin-d-other-vitamins.html
this 2011 randomized, controlled, prospective study from the British Journal of Psychiatry shows that vitamin d supplementation did not improve well-being in a group of over 1000 elderly women compared to a similar-sized control group.
This is a good study, with negative results. I don't think it means that vitamin d is of no use, but rather that it cannot be assumed to have obvious positive effects for everyone. Some of the effects measured in other vitamin d studies may be the result of non-causative associations (e.g. those with various healthier habits and health paramaters may be more likely to have higher vitamin d levels, but the vitamin d is not the cause of this healthiness, it results from it)
However, the data on this issue continues to evolve. There is some good positive data on vitamin d as well, though not enough in terms of randomized, prospective studies. It will be important, for example, to look at whether vitamin d could obviously be an effective adjunct to other therapies for treating depression. Or whether vitamin d alone has little effect, unless combined with other positive factors.
Meanwhile, I still believe that the standard recommended daily dose of 400 IU for vitamin D is too low, and that 1000-2000 IU per day is better.
See my previous post on vitamin d, http://garthkroeker.blogspot.com/2009/02/vitamin-d-other-vitamins.html
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