Wednesday, March 25, 2009

Long-term antidepressant therapy to prevent relapse

Maintenance antidepressant therapy is likely to reduce the probability of depressive relapse. This would involve continuing to take an antidepressant, long-term, even when feeling better. I would restrict such a recommendation to those who have had recurrent or severe depressions. Such maintenance therapy is best indicated for those who have actually had an acute benefit from a specific antidepressant.

I emphasize the importance of psychotherapy and healthy lifestyle change, which also reduce relapse rates (in the case of CBT, for example, the reduction in relapse rate persists long after the course of CBT is over).

This is a 2008 link to findings from the so-called PREVENT study, which showed that 67% of patients on venlafaxine remained well over 2.5 years of follow-up, compared to 41% of patients on placebo:

A weakness of this study is that they did not allow for an extremely gradual taper of venlafaxine in the group randomized to receive placebo maintenance; therefore the worse outcome in the placebo maintenance group could have partly been due to withdrawal symptoms. However, there is a brief discussion of this possibility in some letters from the Journal of Clinical Psychiatry (2008 May; 69(5): 865-866) , and the authors of the PREVENT study make some good points about why withdrawal symptoms are not likely to account for the worse outcome in the placebo group.

There are a variety of older studies showing reduced relapse rates in patients taking long-term antidepressant maintenance. Here is an example, using imipramine:

Withdrawal effects are unlikely to account for the worse outcome in the control group, because the control group actually still received the active antidepressant, but just at a lower dose. The point of this study is that a full dose of the antidepressant is probably required in a long-term maintenance phase.

Here is another study from 1992 in Archives of General Psychiatry, showing significant preventative effects from taking full-dose imipramine over 5 years of follow-up, with or without adjunctive psychotherapy:

Here is a link to a 1990 study in Archives of General Psychiatry showing that full-dose imipramine had substantial preventative effects, moreso than interpersonal therapy, over 3 years of follow-up:

For this study, I need to go back and look carefully over the full text, which I can't find at this moment.

This study is another compelling piece of evidence, from JAMA in 1999, supporting antidepressant maintenance, and it had an excellent design:

It showed that elderly patients who had recovered from a bout of recurrent depression, who then received placebo, had a relapse rate of 90% over 3 years. Treatment with interpersonal psychotherapy alone reduced the relapse rate to 64% over 3 years. Treatment with the antidepressant nortriptyline alone reduced this relapse rate to 43% over 3 years. Nortriptyline plus interpersonal therapy combined, led to a relapse rate of only 20% over 3 years. Withdrawal effects from notriptyline are unlikely to have substantially favoured the nortriptyline group, since the follow-up was over a 3 year period, which is way beyond any period of withdrawal effects.

Here is another 2007 review paper, from The Canadian Journal of Psychiatry, summarizing strong research support that long-term antidepressant therapy reduces relapse rate in major depression by about 50%:

St. John's Wort

St. John's Wort is a herbal antidepressant. Its mechanism is not well-understood, and at this point is in the realm of speculation, but may involve multiple compounds rather than just a single ingredient (one of the many ingredients in St. John's Wort extracts, for example, is hyperforin).

There is an evidence base in the research literature, supporting its use. However, I find many of the articles to be published in minor journals, and to be of questionable quality.

I will restrict my present survey to a few studies that I consider to be of higher quality:

Here is an article abstract discussing possible mechanisms of action:

This is a reference to a Cochrane review from 2008.

It supports the use of St. John's Wort for treating major depression, and concludes that response rates were similar, compared to SSRIs and tricyclic antidepressants. It also concludes that St. John's Wort was much better-tolerated than other antidepressants, with a greatly reduced risk of side-effects or of discontinuing the medication due to side-effects. The authors note that studies from German-speaking countries tend to report a greater benefit from St. John's Wort.

I note that this review was written by authors from a "Centre for Complementary Medicine Research" in Germany. It may be that researchers at such a site could have a biased view in favour of complementary therapies.

This review from the major journal BMJ in 2005 gives much less enthusiastic conclusions about St. John's Wort:

It gives a rigorous analysis of the data, and concludes that there is evidence, mainly from older, smaller, lower-quality studies, that St. John's Wort is beneficial compared to placebo, particularly for mild to moderate depression. More recent, larger, more rigorous studies, and studies including patients with more severe depression, show smaller treatment effects.

It does strongly emphasize that different preparations of St. John's Wort may differ in quality, especially since it is an over-the-counter product in most places, and therefore may lack the guaranteed quality control of regulated pharmaceutical products.

Here are links to 2 carefully done studies from 2001 and 2002, published in JAMA, showing no therapeutic benefit of St. John's Wort. The first study compared only with placebo, the second study also compared with sertraline, an SSRI--in the latter study the sertraline actually didn't do well against placebo either! I have to wonder if particular samplings of depressed patients are relatively less treatment-responsive compared to placebo, for a variety of reasons. Also, it may be that some preparations of St. John's Wort are more effective than others:

Here is a link to a recent German study showing that people who respond to St. John's Wort have lower rates of relapse, compared to placebo, if they continue to take it for a year:

There are some interactions St. John's Wort may have with other drugs; mainly the concern is that St. John's Wort induces the liver to metabolize other drugs more actively, therefore reducing the levels of other drugs. This could be a danger for some people. Here is a reference about this:

There are case reports of St. John's Wort causing mania, so it would need to be used carefully in persons with bipolar disorder. But there are no studies that I can find, which give clear estimates of risk for St. John's Wort to cause mania or rapid cycling, particular when compared to other treatments for depression in bipolar disorder.

There is a poor evidence base looking at the safety of combining St. John's Wort with other antidepressants, but there are a few case reports of possibly dangerous states such as serotonin syndrome.

I will add to this posting later, but for now I would say that St. John's Wort is probably quite safe for most people, and is probably easier to tolerate (in terms of side-effects) than prescription antidepressants. It may be effective, for some people, to treat or reduce symptoms of depression and anxiety. It may reduce levels of other medications, including contraceptives, and may interact with other drugs, so these possibilities have to be considered very carefully, and discussed with your prescribing physician.

Also, I should add that different brands of St. John's Wort may differ in quality, differ in the extraction method used, etc. So if you are going to give St. John's Wort a try, it may be worthwhile to try several different brands. Given the abundance of positive research studies from Germany, it might be worthwhile to try a German brand.

Wednesday, March 18, 2009

How to Quit Smoking

It is difficult to quit smoking.

Here is my summary of the evidence about things that help:

The single most effective treatment to help smokers quit is a new drug called varenicline. This drug works by mildly stimulating a nicotine receptor, while blocking nicotine itself from interacting with the receptor: in this way it is a "nicotine receptor partial agonist." Varenicline is quite well-tolerated, the most common side-effects being nausea and insomnia. Usually these settle with time, and are less a problem if the dose is started low, and built up gradually. There have been reports of adverse psychiatric side effects (e.g. agitation, worsened insomnia, worsened depression) so it would have to be used cautiously in those with mental illnesses. I have reviewed a few studies below which affirm its usefulness among patients with psychiatric problems.

Evidence shows that there is only about a 10% chance of being able to quit smoking on your own (by quitting, we mean staying abstinent for at least a year).

A 3-month course of bupropion (an antidepressant) approximately doubles your chance of being able to quit. However, this raises your chance only to about 20%.

Tricyclic antidepressants such as nortriptyline can increase abstinence rates, probably comparable to bupropion.

Nicotine replacement (e.g. gum or patch) is less effective than bupropion. But it does increase your chances of quitting to about 15%.

Varenicline is most effective of all; a 3-month course increases your chance of quitting to about 25%.

Probably, combinations of the above pharmacological treatments increase your chances further.

Also I should note that many of the studies looking at pharmacological treatments for smoking addiction only used the active treatment for three months. It seems to me that longer courses of treatment would be more likely to help people maintain sustained abstinence; addictions and other long-standing phenomena in the brain persist, or change, over a course of years, not just months.

Psychotherapeutic strategies (e.g. CBT and other behavioural therapies) may help, but the evidence is weaker. The evidence that is available suggests that if psychotherapeutic or motivational strategies are to be effective, they need to be maintained over the long-term (perhaps permanently). In this regard, it reminds me of a "12-step" philosophy, which emphasizes the permanence of an addictive problem, and emphasizes that lifelong vigilance is needed to prevent relapse.

The following study published in CMAJ showed 54% 1-year abstinence in a group of smokers who had suffered an heart attack (MI), and who were given an "intensive anti-smoking intervention" (advice, an hour of counseling, and 7 telephone follow-up sessions over 60 days). The counseling employed "Marlatt and Gordon's relapse prevention model." A similar group of smokers not receiving this intervention had a 35% 1-year abstinence rate. Interestingly, medications were permitted in this study, and were associated with markedly worse abstinence rates. But the medications were administered more or less ad lib, so the effect of medications would be very confounded and unclear (for example, perhaps only the patients struggling most would have opted for medications--the reason they didn't do as well is because they were more severely addicted in the first place, not because of the medications. Also, with a haphazard administration of medications, patients might not realize the need to continue medications longer-term to maintain a therapeutic effect).
In my opinion, the level of "intervention" here actually seems quite minimal, yet it seems impressive that an organized effort of any kind to help prevent smoking through counseling methods would produce good results.

This is the best review article about medication treatments to date, in my opinion; it is from The Canadian Medical Association Journal (July 2008):
A current study by Michael Steinberg et al. in Annals of Internal Medicine (2009;150:447-454) shows that combination therapy with bupropion + nicotine patch + nicotine inhaler, increased abstinence rates at 26 weeks to 35% in a group of medically ill smokers, compared to 19% in a group receiving only a nicotine patch. Those in the combination group were encouraged to use the treatments as long as they felt necessary, then to taper and discontinue as they felt able. This instruction, in my opinion, would have discouraged the participants from considering that bupropion could work to prevent relapse in the long-term, therefore they would probably have chosen to discontinue the bupropion as soon as they felt free of their smoking habit for a short time. As I look at the study in detail, I see that most of the combination group indeed did not maintain the bupropion beyond the 3 month mark. I suspect that if people were strongly encouraged to continue the treatments longer, on a preventative basis, then the abstinence rates could have been much higher than 35%.

Here is a 2005 meta-analysis showing that the tricyclic antidepressant nortriptyline can be effective. Once again, the effects were significant but modest. Most of the studies used only a standard 3-month course of treatment, followed by a taper and discontinuing the nortriptyline. In the one study allowing a full year of nortriptyline treatment, the abstinence rate was much higher (40%):$=relatedreviews&logdbfrom=pubmed

Similarly, in a study maintaining varenicline for 52 weeks, the abstinence rate was 36.7%, compared to 7.9% with placebo. However, while the existing evidence about the safety of using varenicline on a long-term basis is generally reassuring, more long-term experience is necessary with this drug to know for sure. I think the potential risks would have to be weighed against the risks of continuing to smoke. Here is a link to the study:$=relatedarticles&logdbfrom=pubmed

Similarly again, in the one long-term study of bupropion (a full year of medication), there were considerably higher abstinence rates:

The following small study showed that varenicline helped reduce smoking in patients with schizophrenia, and appeared to have some beneficial cognitive effects in this group.

The following small study showed possible increased abstinence rates when varenicline and bupropion therapy was combined:

Another study supporting the idea that combination therapy (e.g. varenicline + nicotine replacement) is more effective than one treatment alone, for helping smokers quit:

The following study shows that varenicline is similarly tolerated and effective in patients with depression, compared with patients without a history of depression. Stress and mood scores improved slightly with time:

This 2009 study from Biological Psychiatry suggests that varenicline could also reduce alcohol consumption in heavy-drinking smokers:

This is a 2009 Cochrane review of smoking relapse prevention interventions; it supports extended treatment with varenicline to prevent relapse, and concludes that there is insufficient evidence at this point to comment one way or another on specific behaviour therapies:$=relatedreviews&logdbfrom=pubmed

This study looked at 20 weeks of adjunctive CBT, and found no significant difference in abstinence rates after a year. But it did find an advantage in the CBT group in the shorter term, during the course of CBT (45% abstinence in the CBT group vs. 29% in the control group, at the 20 week mark). This suggests that long-term, ongoing, continuous CBT may be helpful to boost abstinence rates, but the therapy loses its effectiveness if it is not maintained:

All of these studies support the idea that smoking addiction is a long-term problem. Short-term strategies (typically over a few months) definitely help, but long-term, continuing effort or treatment is needed to maintain abstinence for most people. These strategies could include medications such as varenicline, bupropion, or nortriptyline; and they could include psychotherapeutic approaches such as CBT.

Individuals with psychiatric illnesses such as depression, bipolar disorder, ADHD, and especially schizophrenia, have much higher rates of smoking. Here is a reference:$=relatedarticles&logdbfrom=pubmed

There is evidence that nicotine can acutely improve elements of cognitive performance and to reduce impulsivity, particularly in those with illnesses such as schizophrenia and ADHD. This may be one of the reasons why individuals with these problems are more drawn to cigarette smoking. Here is some evidence:

Also there is evidence that nicotine can improve performance in attention tests in elderly people with dementia:$=relatedarticles&logdbfrom=pubmed

Yet, of course, nicotine has numerous harmful effects. And it is likely that nicotine could cause long-term harm to cognitive function, through several mechanisms, even if it causes short-term enhancement. A medication such as varenicline, due to its agonist effect on nicotine receptors, may be especially helpful to address some of the cognitive or attentional problems in persons with mental illnesses.

In terms of health care policy, I am puzzled about why effective therapies to improve smoking cessation are not publicly funded. Smoking is one of the largest public health problems in the world, and causes an enormous burden of premature disease and death, as well as an enormous financial drain on the health care system. I believe that all proven therapies for smoking cessation should be freely available.

Unfortunately, varenicline -- and other anti-smoking therapies -- are expensive, and they are often not covered by health plans.

Tuesday, March 17, 2009

Psychoanalysis & Neuroplasticity

This post is based in part on my thoughts regarding Doidge's book on neuroplasticity.

Psychoanalysis is a type of psychotherapy in which patients usually attend sessions almost every day (3-5 days per week, 50 minutes each time). The details of theory and practice vary, but in general psychoanalysts tend to believe that early childhood events and memories are very important to examine and understand, and that these events (e.g. relationships with mother) have direct causal links to adult personality traits and psychological symptoms. Also psychoanalysts tend to believe that the relationship with the therapist is a setting in which prior relationship dynamics recur, in the form of "transference." Most psychoanalysts assume a relatively quiet or passive stance, tending not to have active conversation or "problem solving" dialogs with patients. Also most psychoanalysts would tend to interpret various types of phenomena, such as dreams, behavioural habits, etc. as laden with meaning. A course of psychoanalysis might take years, and in general the model would be that the patient would "work through" various childhood conflicts, including as they might be transferentially manifest in the therapy, and that the patient might come to understand the various themes at play in their lives, as manifest in dreams, habits, and interpersonal behaviour. This process of understanding and "working through" is thought to lead to symptom relief and life change.

Doidge himself is a psychoanalyst. One of the chapters in his book describes psychoanalysis as a "neuroplastic therapy." (chapter 9, Turning our Ghosts into Ancestors). Part of the support for his claim comes from a case study (a type of evidence characteristic of psychoanalytic thinking). And part of his support comes from briefly describing the life and work of Eric Kandel, the great nobel laureate neuroscientist.

Kandel's work brilliantly demonstrated some of the specific anatomic and molecular changes that happen in neurons as memories are formed.

Kandel himself has been an advocate of incorporating recent biological scientific knowledge into the practice of psychiatry and psychoanalysis (see:, and had apparently planned to become a psychoanalyst himself.

I consider it not to be particularly relevant to mention Kandel at all, other than to quote someone important who probably considers psychoanalysis a good thing. It is a common sales tactic to mention an important person's name while trying to convince someone of something. Also it is common in medicine and psychiatry--but especially in alternative medicine--for there to be some mention of something that sounds "scientific" to bolster the public opinion of a product, while the science itself, if looked at closely, is only obliquely related. For example, many questionably effective naturopathic remedies, sold at quite a profit, include advertising laden with some kind of biochemical jargon, much of which, at close examination, lacks substance, but which sounds impressive.

I believe that psychoanalysis can be a powerful and transformative experience. However,I also strongly suspect that there are elements of dogma contained within the theory which are irrelevant to its beneficial effects, and which at times could make it an inefficient therapy.

Consider this thought experiment:

Suppose the beneficial effects of psychoanalysis are due to the following factors:
1) meeting with someone for an hour per day, who will listen and try to understand life problems
2) finding an "explanation" for symptoms. In the case of psychoanalysis this explanation tends to come from an examination of early life events.

Suppose that it is the belief in the explanation that causes symptom improvement, therefore that if some alternative "explanation" for symptoms could be developed, then it would lead to the same symptom improvement. Therefore, suppose that the psychoanalytic theory of character and symptom development is actually a fiction, akin to a dogmatic religious belief system, but that adherence to this belief system, and the resultant faith and conviction, would be the causes of symptom relief and character change.

A way to test this would be to conduct a randomized study of two types of intensive, long-term psychotherapy. Both would be 5 sessions per week, 50 minutes per session, lasting 5 years.

Group 1 patients would have psychoanalysis.
Group 2 patients would receive the same intensive, empathic, sessions, with intelligent and thoughtful, well-boundaried therapists. But let us imagine that some other belief system would underlie the therapy for group 2. For example, astrology. Or some form of religious fundamentalism (of any variety). Here, interpretations would be based on the positions of stars & planets, or on passages from religious texts.

A condition for this type of experiment would be that the patients in both groups would have to lack any differences in bias for or against the style of therapy. So, for example, patients in group 1 would have to have a similar level of belief that psychoanalysis is a valid and culturally-accepted system of thought, and have similar respect for the therapist, compared to the beliefs about therapist and therapy style of patients in group 2 (regarding astrology or fundamentalism, etc.).

In both groups, I suspect that subject matter would come up in the sessions, which would require the therapists to respond either empathically or interpretively. There would probably be dreams that would come up, probably interpreted quite differently--or not at all-- in both groups. The process of therapy, dream interpretation, feelings of closeness with therapist, etc. might well be experienced similarly between groups.

My hypothesis is that both the groups would show similar improvement in a 5 year course of therapy, with only a slight advantage for group 1. I believe this is because the core effect of such therapy is not from the theoretical belief system, but from the process, which is caring, consistent, empathic, understanding, and interpretive. Failed therapy experiences may happen in both groups, some of which because the patients do not like the style or belief system which is being introduced, some of which because life problems can be treatment-resistant at times, some of which because the patient did not feel well-matched with the therapist. I think group 1 would do very slightly better than group 2, because despite the dogma involved in psychoanalytic theory, the underlying process is more intellectually open (at its best).

Unfortunately, I think there is a substantial risk for people in both groups to come out of the experience with stronger dogmatic beliefs, irrespective of any therapeutic improvement. In a more mature psychoanalytic frame, I think this risk would be diminished, as the process would hopefully be more intellectually open.

I do believe that we as intelligent creatures should always seek the "truth" as best we can know it, and therefore we need to challenge our dogmas. The best therapies, in my opinion, need to seek such truths without being restricted by dogma. This is consistent with the underlying theme of psychoanalysis, which I think is about liberation (liberation from symptoms, liberation from past harms or traumas, etc.).

I am reminded now of Joseph Campbell, the comparative mythologist, who might argue that the different styles of therapy are something like different mythologies, none of which are literally "true", but perhaps all of which might contain core aspects of wisdom about the human condition. He might also argue that dogmatic, literalistic adherence to any system of belief could obstruct its underlying message. But he would also agree, I think, that one has to have "faith"--a sense of trust, engagement, and belief--in order to have a transformative experience from anything.

In psychoanalysis, I think it is immensely valuable to seek meaning by examining early childhood events, and by searching for meaning and themes in dreams and nuances of behaviour. But I think it can be can be obstructive to believe, literally, for example, that specific non-traumatic events or patterns of engagement with one's mother at the age of 2, are the causes of specific adult symptoms. I consider the greatness of psychoanalytic interpretation to lie in its focus upon a human life as though it is a great novel or work of art, and that the therapy is partly an experience of understanding, analyzing themes, interpreting, looking at context, in order to enrichen the experience of the art.

A weakness in psychoanalytic practice can, in my opinion, be due to its passive approach at times, which can render it less efficient. Another weakness can be due to a dogmatic or literalistic over-absorption with the theory, causing the therapy to digress--sometimes for years--into an examination of early childhood events, when the core elements of therapeutic need lie solidly in the present, or in the more recent past. I think modern psychoanalysis needs to much more actively incorporate ideas from cognitive and behavioural therapies, from social psychology, as well as from behavioural genetics, etc., and to actively question its dogma.

From a "neuroplastic" point of view, I think the immense advantage of psychoanalysis is in the frame, which is intense (5 days per week), long-term (over years), intellectually open (anything that passes through one's mind is encouraged to be spoken), and consistent. If one was taking language or music lessons, we would see MUCH more "neuroplastic change" in the brain (and, much more importantly, we would see much more language or music learning), if the lessons took place 5 times a week for 5 years, rather than just once a week for 6 months. The consistency and discipline of the psychoanalytic frame is powerfully motivational, just as is any other consistent and disciplined educational framework.

Drum Circles

Drum circles are groups where people gather to pound drums together: producing, hearing, and appreciating rhythms.

The perception of rhythm is one of the core elements of human experience.

Over hundreds of thousands of years of human evolution--even before the development of culture--the perception of rhythm must have been a very important part of daily life experience.

Here are some examples of rhythms that have been part of life experience for millions of years:

-The rhythmic pounding of ocean waves
-The beating of the heart (as perceived by feeling the pulses through touch, by feeling a throbbing, excited heart in the chest, or sometimes by hearing one's own or someone else's heartbeat)
-The rhythm of breathing (regular and soft in a calm state, rapid or erratic in anxious or excited states, irregular in various particular ways as a person is crying or sobbing; or when a person is dying, e.g. Cheyne Stokes respiration)
-The chirping of crickets or the croaking of frogs (these rhythms being affected by human proximity)
-The rhythm of work tasks (e.g. preparing some kind of meal or building some kind of structure would involve repetitively pounding, picking, or working with a material, and if this was a monotonous, laborious task, a rhythm would naturally form to help the person "get into it")
-The rhythm of human footsteps (steady and strong when feeling confident and certain, rapid or timid when frightened, stomping when angry)
-The rhythms of the human voice. Before the development of languages over 50 000 years ago, probably a great deal of communicative content between humans would have been based on "non-verbal" vocalizations, which would have emphasized tonal quality but also rhythm. Today vocal rhythms are most obviously part of the expressive content in poetry and song.
-Part of rhythm includes silence. It is the "empty space" between sounds. There was a lot more silence in pre-modern cultures.

Upon the development of human culture, starting perhaps 50 000 years ago, rhythms would have been generated spontaneously as a part of creative expression, as celebration, or as ritual.

In modern culture, perhaps a lot of the ancient, prehistoric aspects of rhythmic perception have been "drowned out". In urban environments, we have a lot of cacophonic, industrial sounds, or multiple sources of sounds all coming at us at the same time. There may not be very much silence at all. I suspect that this cacophony is a contributing factor to life stress, and one of the variables increasing the rate of mental illness (there are certainly many studies showing increased prevalence of various mental illnesses in urban environments). As a corollary, I believe that spending time developing one's musical and rhythmic experiences is beneficial to mental health.

As a therapeutic modality, drumming could help people in various ways:
1) as a form of meditative focus
2) it involves physical action: it is a form of exercise as well as a form of tactile stimulation
3) it helps to focus attention: it is a form of mental exercise, as well as a means to distract mental energy away from anxiety or other negative emotions
4) it can be an endless source of intellectual stimulation, with hearing or producing increasingly complex rhythms and cross-rhythms. This can evolve to become a source of esthetic enjoyment, also leading to appreciating rhythm in other aspects of life and music more richly.
5) it can be a social activity, in which other members of the group can be guides or teachers: in drum circles, individuals need not be skilled in drumming or in generating complex rhythms--exposure to the group permits a social learning experience
6) similarly, a drum circle could be a good setting to deal with performance anxiety or social anxiety, in the comfort of an encouraging and accepting group
7) it can simply be a healthy, enjoyable form of stress management
8) drum circles can be a means to build community: the experience combines elements having to do with conformity (maintaining the same rhythm together) and with individuality (each person may have a separate or special rhythmic role or task) -- both such elements are required to have healthy community life

In Vancouver, I know of one regular drum circle group, which has been open to anyone interested. The leader of this group, Lyle Povah, has done interesting work with drum circles as part of an inpatient eating disorders treatment program. Here's his website:

There may be similar groups in other communities across the world, and I encourage people to research this, and to consider checking one out.

Friday, March 13, 2009

Doidge (Neuroplasticity) review - part 3 (Schwartz)

Doidge devotes a chapter to discussing obsessive-compulsive disorder. He claims that a treatment developed by Jeffrey M. Schwartz is "plasticity-based". The implication is that other psychological treatments for OCD are NOT "plasticity-based."

Schwartz has published articles in the literature going back into the 1980's looking at OCD patients using PET imaging.

I do not find any good study in the literature about Schwartz's particular technique, as published in his book, in particular no study comparing his technique with CBT.

Also the theory is presented that OCD is caused by a failure for the caudate nucleus in the brain to "shift gears automatically", and that the therapy described is a means of "shifting gears manually." While there are a variety of brain metabolism changes in OCD, I think it is an overly strong statement to believe that this is literally true. One could use the idea of the "caudate gear box" as a metaphor, but it may be quite inaccurate, or at least poorly supported by clear evidence, to be taken literally.

So it concerns me that the chapter in Doidge's book about the "brain lock" approach is more of a book plug than something founded on solid evidence. Doidge could well have made the case that CBT is a type of "neuroplasticity-based treatment". In fact, there is good data to support such a case--including numerous imaging studies--and including a recent paper which Schwartz himself co-authored, which shows various regional changes in brain metabolism associated with improvement in OCD symptoms from intensive CBT:

Yet, I think it is important to be open about any new therapeutic idea--it may be that the "brain lock" therapy for OCD could be helpful to many people. It's just that Schwartz's book has been given an endorsement by Doidge without a convincing amount of good evidence, while minimizing the robust evidence favouring CBT.

Doidge (Neuroplasticity) review - part 2 (Taub)

Doidge devotes a chapter to the work of Edward Taub. I think Taub's ideas are simple but brilliant. He developed a treatment called "constraint-induced movement therapy" which appears to be remarkably effective to help with recovery from strokes and other injuries.

The simple idea is to restrain the normal limb, almost continuously, for at least weeks at a time, after a neurological injury. Otherwise, the normal limb will compensate for the affected limb. If the normal limb is constrained, the brain itself will develop new pathways to improve the function of the affected limb.

This treatment has good evidence-based support:

{this 2008 study is from Lancet Neurology, one of the top journals in neurology}

{another very important study from 2006 in JAMA}

I'm curious about the applications of this sort of therapeutic idea to psychiatry. Psychiatric symptoms can be like other neurological impairments, and the psychoanalytic phenomenon of "defences" may be analogous to the tendency for a neurologically-injured person to favour the non-affected limb, while the affected limb loses more and more function. A psychological therapy which challenges defences may be something like a Taubian "constraint-induced movement therapy" for the mind.

Importantly, in order for Taub's therapy to work, the constraint has to be applied almost continuously during waking hours, for at least weeks at a time. It is an immersive experience. It is an interesting challenge to find more psychological therapies that can be "immersive" in this way.

Doidge (Neuroplasticity) review - part 1 (Merzenich)

This post begins my review of Doidge's references from his book on neuroplasticity.

The first references I have looked through pertain to the work of Michael Merzenich. He has done very interesting research, dating back 4 decades, a lot of it having to do with studying the auditory cortex, and how it changes in response to stimulation of various sorts during different phases of development. Also he done major work researching and developing cochlear implants for treating hearing loss.

His 2006 article about using a "brain plasticity based training program" to improve memory in older adults ( is interesting and encouraging, yet it warrants a close look at the actual results: the memory improvements from this technique were very modest (though significant), also the control groups were both quite passive (one group just looked at DVD videos, the other had no "intervention" at all). It would have been much more interesting to me to see an active control group in which the individuals would be doing simple memory exercises or other active intellectual stimulation for the same length of time. Because this type of active control was absent, the results may aggrandize the specific form of skill training described in the study; this skill training regimen is now being marketed, and money is surely disappearing from the pockets of many people, including many elderly people who may not have an abundant financial reserve. This makes me especially less enthusiastic about the results. I have no doubt that active mental exercise changes the brain through "plasticity" but I have to wonder if we have to sign up for the deal ("save 20% and get free ground shipping!") with this specific technique to achieve this. Perhaps signing up for a book club, memorizing poetry, and playing chess daily, would accomplish similar results. I would like to see what the evidence has to say about this. His website is interesting to look at, has a few mental exercises to check out, the style of which I think really is quite positive and imaginative. I will be curious to see if his approach--and variations of it-- could be specifically helpful in treating disorders such as autism. But I don't see good clinical data out there yet.

As an amateur musician, I have found that "ear training" is probably the most important, but often least taught or practiced, form of mental development for improving musicianship. Merzenich's exercises clearly focus on "ear training" as a significant component. Here's his website for you to check it out yourself:

Here's a link to a program you can acquire, designed for music students, which develops musical ear-training ability much more thoroughly, in my opinion (I recommend this to all musicians):

Tuesday, March 10, 2009


This is an important book which I highly recommend:
The Brain that Changes Itself, by Norman Doidge (Penguin, 2007).

Doidge is a psychoanalyst who has done a fine job compiling evidence from recent neuroscience research, and from some older but neglected neuroscience research, that the brain has a tremendous capacity--a capacity which is arguably its most basic, core, innate quality-- for change and adaptation.

The idea of the brain as permanently "hard-wired" is refuted, with solid evidence.

Many of these ideas I have always felt to be obvious truths. For example, it seems an obvious necessity that the brain would have to build new connections in order to form any new thought, experience any new feeling, store any new memory, learn any new skill. But the degree to which whole areas of the brain can "re-wire" themselves is extremely interesting, and the evidence Doidge presents is very convincing.

Also, it has always been an obvious truth to me that any kind of sensitive neuroimaging device would of course demonstrate changes following a successful course of therapy (or of any other sort of learning or substantive life change).

The therapeutic applications based on this book are numerous, here are a few I can think of:

1) structured, intensive practice could lead to far greater effects than what has previously been assumed. The brain itself, as well as people in society, informed by culturally-based attitudes, tend to "work around" problems if the situation allows, whereas it can be the case that the problems themselves can be solved directly under the right conditions. For example, if an English-speaking person moves to a small town in a foreign country, that person will quickly learn that new foreign language, if it is necessary in order to survive. But if there are numerous English speakers in that small town, that person may not learn much of the new language at all.
We may need a type of immersive, constrained experience in order to compel our brain to develop a new faculty.

2) structured, intensive activities that have become part of a cultural norm (e.g. internet use, TV watching, etc.) could substantially alter the brain's connectivity and functionality, to optimally adapt to these new media. This could serve us well, culturally--but it may come at a cost of reduced functionality in media away from the TV or internet, particularly with respect to sustained attention, other intellectual and emotional faculties, and various types of social interaction.

3) Addictive processes are fed by the brain's capacity to adapt, to "re-wire" itself to expect a frequently reinforced behavioural pathway. "Un-learning" addictive behaviour once again may require a massive amount of work, akin to learning a new language.

--I have yet to review all of the references cited in this book. I think the primary source data will be important to go through in detail. There are some areas and claims that I think may possibly be overstated, in my opinion. But first I would like to review the evidence directly. I actually find the term "neuroplasticity" somewhat annoying, especially when therapeutic ideas are labeled "neuroplasticity-based treatments", etc. --I would say in response that ALL therapy, of ANY sort, is of course "neuroplasticity-based", so such lingo is unnecessary, and rings of salesmanship to me (indeed, there are several corporate ventures mentioned in the book). What matters most is the new types of therapeutic ideas that have been conceived by some of the researchers cited in the book, and how well they can work for very entrenched problems.

In the meantime, I do recommend Doidge's book highly.

Friday, March 6, 2009

Physicians in need of help

There is a high incidence of psychiatric problems in the medical community. Physicians may have a difficult time finding help. There are a variety of reasons for this, the most common of which is that the sources of help may all involve people the physician knows personally.

In BC we have something called the "physician health program", which is a resource especially for physicians in need of help. Here is the website:

Hopefully other communities have similar programs.

If a hospital admission is needed, it may be desired to arrange this in a different place, if privacy or confidentiality issues are major concerns.

Thursday, March 5, 2009

Exercise benefits Quality of Life

You can click on the chart to expand it; the chart above is from a randomized, controlled, 2009 study by CK Martin et al., published in the major journal Archives of Internal Medicine, in which 6 months of regular aerobic exercise is shown to improve numerous domains of quality of life, including mental health, vitality, and social functioning, in a group of 430 sedentary postmenopausal women.

To interpret the chart, look at each symptom domain. There is a control group (which did not exercise), then groups which exercised approximately 1, 2, and 4 hours per week, with the groups which exercised more represented towards the right-hand side of the chart.

The improvement in quality of life did not depend on any weight loss occurring with the exercise. And it appeared that as little as an hour a week of exercise was beneficial, though 2-4 hours per week were slightly more beneficial than just one. Here's a link to the abstract:

As a cautionary note, I find "exercise addiction" to be another potentially serious problem, which could substantially REDUCE quality of life. The above data support a very modest amount of exercise, in the order of 4 hours PER WEEK , for improving quality of life.

I strongly encourage people to exercise. I believe it is basic self-care, a requirement for health.

It is intuitively obvious that exercise would be beneficial for psychological health, and be a good potential therapy for depression or anxiety.

Yet, there is an important recent study of over 5000 Dutch twins, which shows that exercise did not have a direct influence on anxiety or depression. This is a surprising result, but it needs to be taken seriously. Twin studies are very powerful in research, since they look at individuals who are genetically identical -- any differences in symptoms would have to be caused by environmental factors, as opposed to genes. Twins who exercised more than their co-twins were not in fact any less anxious or depressed. (Actually, as I look at the results directly, I see there was a small association, but it was judged to be "non-significant")

The study did confirm that people who exercise are, on average, less anxious and depressed than those who do not exercise. But the conclusion was that this is not because exercise improves emotional symptoms -- it is because there is a genetic factor which predisposes some people both to exercise more, and to have fewer psychological symptoms.

Here is a link to the study:

On the other hand, there are a few studies which show a therapeutic effect of exercise on psychological symptoms:

The above studies show a beneficial effect of exercise, of at least 3 times per week, 30 minutes per session.

Why are there seeming contradictions with these studies?

It may be because the twin study was looking at individuals' intrinsic exercise behaviours, as determined by their life circumstances & inherited factors. Variations in exercise between twins may have been due mainly to opportunity or chance.

The other studies were looking at exercise as a formally prescribed treatment. This would involve a directed change of behaviour, outside of what the individuals would normally do on their own.

It could be that prescribed changes of behaviour, if adhered to for health reasons, could have a stronger therapeutic effect than the behaviours engaged in for other reasons.

Active Placebo Studies show smaller benefits from Antidepressants

In most of the better clinical studies, a "placebo group" acts as a control. The placebo would consist of something totally inert, such as a capsule with nothing inside, or possibly with a small quantity of a sugar such as lactose.

The idea of an "active placebo" is interesting: in this case, the placebo is an agent shown not to have any beneficial or detrimental effect on the disease in question, but which clearly has side-effects.

An example would be using a tablet of Gravol (dimenhydrinate) as the "placebo". It is not an antidepressant, but it has side-effects (sedation, dry mouth, etc.). In this way, it is a more convincing placebo, since a person taking an agent which produces side effects is more likely to believe that they are taking the "active" agent. If a person is taking a placebo they strongly believe to be a placebo (since it produces no side effects) they are less likely to have any "placebo effect" response, and the whole point of the placebo control will be relatively "unblinded."

There is a body of research literature looking at using "active placebo" vs. antidepressants to treat depression.

{a 1998 meta-analysis from the British Journal of Psychiatry showing that the effect sizes of antidepressant therapy are only about half as large when compared against an active placebo, rather than an inert placebo}

{a 2004 Cochrane review with similar findings}

These results support the evidence that antidepressants work -- but they suggest that probably most of the studies overestimate how well they work, because they are measured against inert placebos in most cases.

I think that more clinical studies need to include active placebos.

I post this not to be cynical, or to discourage the use of antidepressants--as you can see from the rest of this blog, I strongly support medication trials to treat psychiatric problems--but I believe that we have to always search for the most accurate, least biased sources of information. We need to be wary of exaggerated claims about the effectiveness of anything, especially since I see in my practice that many of the treatments don't seem to work quite as well as the ads claim they should.

Wednesday, March 4, 2009


Trazodone is another antidepressant introduced in the early 80's. Once again, its use was fashionable for a time, gradually faded, and at this point it is mainly used adjunctively to treat insomnia.

It is notable among antidepressant choices in not causing sexual side effects (other than the rare incidence of priapism, which is a medically dangerous, painful, abnormally sustained penile erection, which occurs in probably less than 1 in 1000).

The trouble with trazodone is that for many people, it causes too much daytime sedation. However, it can be worth a try, to treat insomnia associated with depression or antidepressant therapy, or possibly as an augmentation to treat depression or OCD.

In my experience, about 50% of people find trazodone a helpful adjuct, but the other 50% find it causes too much tiredness or dizziness the next day to be worth continuing.

Here is a literature review:

{in this 2008 study from a minor journal, trazodone was shown to increase the amount of slow-wave sleep in treating chronic insomnia}

{a 2003 urology article showing evidence that trazodone may help treat erectile dysfunction, especially at higher doses}
{a small 2008 study showing that 50-100 mg of trazodone may reduce SSRI-induced sexual dysfunction}
{a small 2006 study showing equivalence between trazodone and sertraline in treating depression over 6 weeks}
{a small 1999 study from a podiatry journal, showing that trazodone can help with painful diabetic neuropathy symptoms}
{a 1994 American Journal of Psychiatry article showing that trazodone can help with antidepressant-induced insomnia, particularly helping with overall subjective sleep quality, reducing waking in the middle of the night, and reducing early morning waking}

{this awkardly-designed 1996 study suggests that combination treatment including 100 mg of trazodone may help in treatment-resistant depression}

{this quite weak 2001 study nevertheless suggests that trazodone helps to reduce nightmares in PTSD patients}
{an early, 1983 study, of trazodone vs. imipramine for treating moderately to severely depressed outpatients. Despite the weaknesses of the study design, it did have some follow-up over 3 years, showing that trazodone works well for some people, and worked as well as imipramine overall}
{an example of a small study suggesting that adjunctive trazodone could help improve OCD symptoms. Some studies have shown no anti-OCD effect with trazodone alone, but others have shown trazodone alone to be beneficial in refractory OCD. In any case, I think the evidence base suggests that trazodone could at least be worth a try, either together with an SSRI, or even on its own.}

Irrational Numbers Metaphor

This is kind of a whimsical post, perhaps you may find it of very questionable relevance to a psychiatry blog.

I invite some input from any number theory experts out there, perhaps some of my thinking about the following subject is erroneous.

Irrational numbers are numbers which cannot be expressed as a ratio of integers. So, for example, the square root of 2 is irrational (it is approximately, but not exactly 1.414; it can be visualized as the distance diagonally across a square which has each side of length=1). The number pi (the ratio of a circle's circumference to its diameter) is irrational, approximately 3.14. The natural exponential base e is irrational, approximately 2.7. If we attempt to express an irrational number in decimal form, we can only ever get an approximation. The digits will keep on going forever, in a non-repeating fashion.

A hypothesis I have about the digit expansion of an irrational number is that the sequence represents a form of true randomness. At one point I did plot out the frequencies of digits in an expansion of pi to a million digits or so, then performed some statistical tests on this, and determined that the results are consistent with random ordering. They MUST be "random", for if they weren't, the number could not be irrational. I would invite a number theorist to show me a proof of this. My idea about randomness invites a philosophical, or mathematical, discussion, about what the meaning of true randomness really is.

But the digits of irrational numbers are calculable. That is, the millionth, or trillionth, digit, in the decimal expansion of pi, can be determined, systematically, through various algorithms. The number e can be calculated in a number of ways (this is a way I discovered as a child, playing with my calculator: take (1+1/n) multiplied by itself n times, with the calculation becoming more and more accurate as n grows larger--only perfectly accurate, though, when n reaches infinity).

So, I am claiming that the digits are calculable, yet randomly ordered. This is a seeming contradiction.

However, I believe there is no simple formula for the "nth" digit of pi. In order to get the "nth" digit, at least n arithmetic steps must be taken. That is, computational work must be done in order to do the calculation, and more computational work is required in order to reach a more precise result, which is at least linearly proportional to the level of precision desired.

Since all computational work requires energy, and there is a finite amount of energy available in the universe, let us suppose that we use all the mass-energy of the universe to perform computational work to determine as many digits of pi, for example, as is possible. (this would involve, in our thought experiment, harnessing all of the great nuclear energies from the stars, etc. to power a computational device just for this task)

Now, having generated all of these digits (I suspect there would be over 10^1000 digits generated, using all the energy of the universe efficiently for this task), we still only have an approximation to the number pi. The NEXT digits of pi are theoretically calculable, but cannot be calculated or known, because we have used all available computational energy.

Thus, we have calculable digits, which yet cannot be known, because there is not enough energy in the universe to do the calculations to know them.

There is something almost mystical about this: any sequence of digits, for example, randomly conceived in the mind, must correspond to a sequence of digits in the unknowable expansion of pi (in that realm over 10^1000 digits into the expansion), based on the laws of probability.

Something that we can prove is outside the realm of human knowledge is actually part of the ordinary daily products of our imagination.

As an added concept related to this, imagine what your entire life history would look like, translated into a sequence of digits -- perhaps this would include a few thousand pages of text, a few million images, together with the entire sequence of your genome, all transformed into a digit sequence, maybe a few trillion digits long.

It can be shown that this sequence -- an intimate representation of your identity -- must occur at some point in the decimal expansion of all irrational numbers, including pi. (suppose the sequence representing your life story is 10 trillion digits long; then the probability of your sequence occurring starting at or before the nth position in pi's expansion is 1-(1-1/(10 trillion))^n, assuming that pi's digit expansion behaves as a random sequence. With this assumption, once you are into pi's expansion by 10 trillion digits, there's a 63% chance that your sequence will have shown up (interestingly, this probability is approximately 1-1/e). And the more digits you go into pi's expansion, the more likely it is that "your" sequence will show up; this probability converges towards 100% as the number of digits approaches infinity. Actually, we could go on to say that "your" sequence actually recurs, an infinite number of times, in pi's expansion!

In our imagination, we can conceive an ideal circle, and we can imagine the ratio between its circumference and its diameter. That is pi exactly. We have imaginatively visualized something, with perfect precision, something that cannot be expressed logically with perfect precision.

There is a life lesson in this, I think. Be open to possibility. That which is seemingly impossible may require an imaginative re-framing to see that it was always in front of you, available to you, part of "ordinary" daily life. And there can be more to simple relationships than meets the eye -- dividing a circumference by a diameter yields a number which contains information paralleling all known information in the universe, including the story of yourself.

Tuesday, March 3, 2009

Moclobemide is a Good Antidepressant

The antidepressant moclobemide is a reversible monoamine oxidase inhibitor. Once again, this is a drug that was frequently prescribed for a time, but has subsequently faded in popularity.

It was released in the late 80's; around 1990 many studies came out, comparing moclobemide with other antidepressants, including tricyclics and fluoxetine, showing that it worked just as well for treating depression. Many of these studies were published in Scandinavia. There have been very few clinical studies since then. Part of the reason may be that moclobemide was never approved in the U.S. (I do not understand why not).

Moclobemide has also been used effectively to treat social phobia.

In my opinion, it is a neglected option in treating depression. Because it has faded in popularity, it is usually tried as a third-line medication. For this reason, it is prescribed to patients who are more likely to have a more refractory depression. For this reason, it is less likely to be seen to help as much; this leads to clinicians pronouncing it ineffective, and not prescribing it. If it was prescribed as a first-line agent, I think we would see that it works pretty much as well as any other antidepressant.

Its advantages relate to the side-effect profile: its side effects in general are probably closest to placebo among all the antidepressants. And there are minimal or no sexual side effects with moclobemide, compared to the SSRI's. Here's a reference:

Other references:
{a 2006 meta-analysis showing that moclobemide works as well as SSRI's}
{a 2006 article from the British Journal of Pharmacology suggesting that moclobemide may have neuroprotective or even neurogenerative effects in the hippocampus}
{a 2003 review}


There was one case series study published in 2000 by Magder, Aleksic, and SH Kennedy, describing the successful use of very high-dose moclobemide in combination with lithium and/or trazodone for treatment-resistant depressed patients. The doses used were up to 1500-1650 mg/day, which is much higher than the usual maximum of 600 mg. They advocated using an MAOI diet at these doses. Moclobemide was well-tolerated, and the patients appeared to benefit over 1-2 years of follow-up. It's worth looking at this brief article in its entirety, here's a link to the abstract:

Volunteering Improves Mental Health

Altruistic volunteering is beneficial for mental health.
There are several mechanisms by which this could happen:

1) the experience of giving one's time and energy for another in need is an intrinsic life joy
2) there are opportunities to build new friendships, with others who also are "practicing altruists"
3) the experience may allow you to discover new aspects of yourself, in terms of skills, pleasures, ambitions, etc.
4) the structure of the volunteer experience may be a "benevolent structure" motivating action in your day, challenging depressive symptoms which might keep you inactive or alone

Here is some evidence from the literature:
{this 2008 study from a gerontology journal, shows that people in their 60's who volunteer moderately have higher levels of well-being, after controlling for variables such as educational level, physical health, etc. People who didn't volunteer, or people who volunteered "too much", had lower levels of well-being}
{a 2008 study from the London School of Economics, showing that there is a direct causal relationship between volunteering and happiness; weekly volunteering increases the likelihood of being "very happy" by 16%, independent of income level--the data also suggest that the effect is more pronounced for people who volunteer more frequently}
{a 2001 study looking at data from 2681 people, showing that volunteering is associated with increased well-being in numerous domains, including happiness, life satisfaction, self-esteem, sense of control over life, physical health, and depression}
{a 1998 study showing that volunteering bolsters well-being in elderly persons who volunteer; also the people who are helped by the volunteers had reduced amounts of depression}

I think there should be some more prospective, randomized studies of volunteering and other altruistic activity in the treatment of mental illnesses.

If you are interested in volunteering in Vancouver, here is a place to start looking: