Wednesday, December 17, 2014

Marijuana: effects on memory

In order to show the effects of cannabis clearly in a research study, it is of course best to have a prospective, randomized, controlled experiment, conducted over a long period of time.

This would not be ethical in humans.  In fact, I don't see that it was particularly ethical in monkeys either.  But Verrico, Gu, et al. did such a study, published in the April 2014 edition of The American Journal of Psychiatry,  giving adolescent rhesus monkeys daily IV doses of THC  5 days per week for 6 months.  A control group, matched for baseline cognitive performance, received IV infusions with no THC.

They found significant impairments in spatial working memory in the THC group.

This is strong evidence that marijuana has negative effects on cognition in adolescents.  It did not prove that there are lasting cognitive deficits after the THC has been metabolized out of the body.

We can conclude from this study that daily heavy THC use in otherwise healthy adolescents is likely to interfere with optimal cognitive performance, which could impair schoolwork and possibly contribute to cumulative risk of various other developmental deficits. 

The study does not address risk to cognitive function in adults.    And it does not address the possibility that THC may be useful for managing other symptoms for some individuals, despite the side-effect of spatial memory impairment.   

Evolution & Psychiatry

It is richly interesting to consider the impact of evolutionary processes as they pertain to human behaviour and psychiatric phenomena.

This is an area which is, of course, laden with controversy.  Yet I find the controversy quite unnecessary, perhaps a reflexive reaction which itself could be understood in evolutionary terms.

Despite having several science degrees, including many courses in biology (including genetics and molecular genetics) I am embarrassed to admit that, during my undergraduate years, I never read major popular books by evolutionary theorists.  It is only recently that I have read The Selfish Gene by Richard Dawkins.   I was well-versed in textbook science, and even laboratory-based genetics, yet the joy of learning about genetics can be savoured much more deeply by taking a look at some of these popular works on the subject.

I do not find the subject matter of The Selfish Gene the slightest bit controversial.  I understand why some find it controversial, but I see this as mainly a product of simple human resistance to adapting entrenched beliefs (some of which have been around for millenia, and considered sacred) in the face of strong contrary evidence.  In this case, some of these entrenched beliefs touch on themes relating to religion and ethics.  It is similar to renaissance astronomers being met with disbelief or condemnation, following discoveries about planetary motions which were quite different from previous views.

Actually, as with most science, I find the subject of evolution to be delightfully, joyously interesting, and certainly not a threat to the culture's moral fabric, etc.     Understanding processes of nature need only increase one's sense of wonder and awe, not somehow render it more "spiritless."   My only objection to The Selfish Gene and other similar books is the use of the term "Darwinism."  While I admire the work of Darwin very much, I don't find that it is necessary or useful to attach his name to a system of understanding nature.  Attaching his name makes the subject sound like some kind of philosophical or political opinion (such as  "Calvinism" or "Marxism"), or a type of esthetic or artistic style.    The science of evolution is similar to the science of arithmetic, geometry, or physics.   We would not call a mathematician or physicist a "Pythagorean" or a "Newtonian."  

Evolutionary theory is a simple application of clear logic to a system in which phenomena are replicated.  Those phenomena which replicate more abundantly become more widespread in the population.  This is a self-evident truth, which leads in more complicated systems to some very interesting mathematics.   As Dawkins points out, this type of replication occurs in genes, but also in culture as "memes."   The application of game theory analysis to such replicating systems leads to an understanding of equilibria between competing strategies, which can persist in any population or culture.  Fluency in mathematics makes an insightful understanding of evolutionary science much more clear. 

How is this relevant to psychiatry?    An evolutionary analysis of behaviour reminds me a little of a psychoanalytic exploration of "the unconscious" -- it can bring to awareness behavioural tendencies that are favoured "as if" the genes themselves had a selfish motive.  Genes, being chemical entities, do not literally have motives, but the fact that they replicate leads to gene frequencies and genetically-based behaviours occurring as if they had motives.  Similarly, the "unconscious" could be understood as silent forces within the mind which guide action, outside of awareness.  Therapeutically, according to psychoanalytic theory, insight about one's unconscious motives can lead to a greater freedom of will, and to an escape from recurrent traps of symptoms.  Similarly, awareness of the "forces" caused by natural selection of genes can help us decide whether to culturally over-ride these forces, for the betterment of ourselves or of society.    For example, as Dawkins pointed out, biology itself cannot be relied upon to produce widespread altruism, and to produce an end to warlike or aggressive behaviour;  such a state can be shown mathematically not be an "ESS" (evolutionarily stable state).  So if we are to aim for widespread peace and altruism, we must culturally over-ride innate biological tendencies, on a personal and population level, and work to teach peace very actively.

For such a project to work, we would have to anticipate its meme-like properties, and be prepared to deal with ensuing problems.  For example, in religious cultures, the meme-like nature of associated beliefs and behaviours can cause deleterious cultural changes as a result of "natural selection."  While many religious beliefs are characterized by a deep sense of fairness, justice, peacefulness, and altruism, the memetic properties needed for beliefs to "propagate" lead to a high likelihood of negative elements, such as magical thinking, instilling fear of hell, suppressing contrary views despite strong evidence, espousing violent actions as sacred elements of following or defending one's faith, etc.   Religious memes can become "symbiotic" with memes for political power or influence, leading as we have often seen to religions and governments combining their influences to dominate a nation's political affairs. 

Tuesday, December 16, 2014

CBT vs psychodynamic therapy for Social Anxiety Disorder

In the October 2014 issue of The American Journal of Psychiatry we see an article by Leichsenring et al (18 authors!) comparing the outcome of social anxiety patients who had received either CBT or psychodynamic therapy.  The patients had about 25 sessions of either therapy, over about 9 months time.  They were followed up over the following 2 years after treatment ended.

The study shows that both groups improved similarly over 2 years:  about a 70% response rate, and a 40% remission rate.

But, huge weaknesses in the study here!

1) No placebo group!  
2) No documentation of the homework done in CBT.
3) No detailed description of how the psychodynamic therapy differed from the CBT, other than a passive reference to the technique or manuals used.

I feel that psychodynamic theory is similar to religious belief or theology:  it is finally a set of cultural practices, couched in a therapeutic milieu.  The actual beliefs are substantially fictional, but are grounded in basic ethical principles expressed in scholarly or literary language.    Similar to a great cathedral, a poetic section of a religious text, or a beautiful hymn, the therapeutic impact comes from the esthetics and earnestness of the fellow practitioners, mixed together with the style being a largely accepted cultural norm.  Fragments of accurate science are blended with fictional but culturally vivid therapeutic dogma (e.g. references to Greek mythology), a product of the testimonial accounts and opinions of strong-minded and literary thinkers, who yet are often poor scientists.  In some ways, it is akin to a medieval alchemist or astrologer, whose theories are mostly fictional, but who may still have a loving and intimate appreciation of their subject matter.  In psychodynamic therapy, there would clearly be a sense of attachment, security, a type of friendship or mentorship (even though these qualities would be normally never be admitted, except as "transference"), and an earnest focus on improvement.

In CBT, many of these same factors would be present, though in a more "coachlike" form.  One of the problems with CBT is that the cultural esthetics of the therapy is largely absent, compared to psychodynamic therapy.   If we compare CBT and psychodynamic therapy to religious denominations, it would be as if CBT would have its meetings in an accountant's office, while the psychodynamic sessions would take place in an environment laden with cultural symbolism, such as a church or cathedral, with musical or poetic accompaniment.  

So one of the strong therapeutic elements of psychodynamic therapy (the "cathedral-like" intellectual esthetics) is compellingly absent in most CBT.  I suspect some of the newer forms of CBT, such as mindfulness-based CBT, are introducing some more of this esthetic element, leading to improved effectiveness.

In treating anxiety of any sort, it appears obviously true to me that the therapy must involve the patient having many hours of practice facing anxious situations.  It is limited how much of this practice can actually take place during a CBT session.  Most of the practice would have to take place as homework.  As I have said elsewhere, psychotherapeutic change in many ways is akin to language learning, or to learning a physical skill or sport.  You can have your weekly lessons with the coach, but most of your improvement will take place if you diligently practice every day.

In this study, there was no mention of this most essential therapeutic agent of all:  the practice done, to face social anxiety situations!  Even in psychodynamic therapy,  I would expect that the therapist would facilitate exposure practice between sessions, even if this was not deliberately prescribed.  In some ways, with a resistant patient, a sensitive psychodynamic therapist could be more effective than a CBT therapist to do such encouragement effectively, just as a good priest may simply have a more effective interpersonal manner to encourage someone in a time of distress, compared to a good accountant.  

But no mention was made of how much the patients actually practiced their skills to manage social anxiety.

I find it quite incredible that 18 scholars, all touting their doctoral degrees in the author list, were required to produce such a trivial paper. 

Varenicline plus Bupropion for smoking cessation

Rose and Behm have shown in their November 2014 article in The American Journal of Psychiatry that 12 weeks of a combination of varenicline 1 mg twice daily combined with bupropion 150 mg twice daily, led to substantially improved abstinence rates for highly nicotine-dependent smokers. 

Most smoking cessation strategies have led to quite low abstinence rates.  A typical outcome would be a 25% probability of quitting after a determined attempt.  This is the first study I've seen that shows a strategy that leads to a 50% abstinence rate.  In fact, they found that the combination works best for the heaviest smokers who were most addicted. 

With smoking cessation, as with many other problems, I think that if a pharmacological strategy is considered, why not try the most effective strategy first? Why not try this combination first, rather than trying one much less effective treatment at a time?

Some remaining questions I have about ongoing management would be to question whether long-term varenicline could be necessary (e.g. for a year or more). 

And, with smoking, a big question now concerns the potential benefits and risks of e-cigarettes.  These are probably good harm reduction aids for many smokers, but on the other hand are addicting on their own, and could initiate dependency problems in young people who try them before smoking at all.   Overall, I think e-cigarettes are an important positive development to help people quit smoking, and also to help deplete the tobacco industry further. 

Quetiapine for borderline personality -- journal article review

This is the first in a planned series of posts to summarize a few interesting articles from psychiatry journals published in 2014.

We begin with an article by Donald Black et al.from The American Journal of Psychiatry 171:1174-82.

It's a very simple 8-week randomized controlled study of treating borderline personality patients with either quetiapine XR 150 mg daily, quetiapine XR 300 mg daily, or placebo.  There were about 100 participants in all.   DSM-IV criteria were used for the diagnosis, and the participants could not have active substance abuse, or be in the midst of a major mood or anxiety episode, etc. 

The "Zanarini scale" was used to track symptom changes.  As I look up this scale, I find it appears to be a simple distillation of DSM-IV criteria, with raters giving each item a numerical score.   Unbelievably, I find that I cannot actually look at the questions directly (a fee of over $40 is requested!), which is quite surprising for what amounts to a small collection of very simple questions.

Nevertheless, the quetiapine groups did better than the placebo group on the borderline symptom scales.  But they did not do compellingly better on broader scales including the Sheehan Disability Scale or the GAF.    There was no advantage of the 300 mg dose over the 150 mg dose.

A few criticisms:

 1) I see the placebo group actually had lower baseline symptom scores, which could have biased the placebo group to show less improvement (e.g. through regression to the mean contributing to the larger symptom changes in the other two groups).     The fact that the graph given in the article showed only symptom change, rather than total symptom score, would have further hidden this bias from the reader.  The error bars were not shown in the graph of symptom change.   I see that the total symptom scores are not shown anywhere in the paper! I'm surprised this got past peer review in a major journal!

2) While 150 mg is considered "low dose" here, it would be useful to see what the effect of 25 mg or 50 mg would be. 

3)  As usual with studies of this sort, it is only 8 weeks in duration.  I would be interested in seeing a duration of at least a year.  This would be relevant not only for evaluating effectiveness (including symptom improvements and dropout rates), but also for evaluating side-effect risks (such as weight gain and metabolic changes).

4) The question is not addressed as to whether the more expensive quetiapine XR preparation is actually needed, compared to the less expensive regular quetiapine.  

In summary, a simple, mediocre study, which lends modest support for a practice that most practitioners probably already have done for years anyway -- which is to offer borderline patients treatment with low-dose atypical antipsychotic medications.