Wednesday, December 31, 2014

Internet Addiction

Most of us can understand the phenomenon of "internet addiction."    We can easily end up spending too much time on the internet, or on other electronic gadgets.  An interesting documentary called "Web Junkie," which is set in Shanghai, is a good introduction to the subject.  This documentary also illustrates some interesting elements of therapeutic care in China:  on the one hand, there is sort of an authoritarian, militaristic boot-camp style (epitomized by the doctor who runs the clinic).  Yet on other hand, there are some calm, gentle, patient, quiet therapists shown (such as the one female doctor). 

A recent meta-analysis by Cheng and Lee (*) showed that rates of internet addiction in different countries ranged between 2% and 10%.  Interestingly, rates were lower in countries with a higher quality of life, such as in Western Europe, and rates were much higher in countries with lower quality of life. 

Restriction of children's internet use by parents is associated with lower risks of internet addiction (**).    Low satisfaction with family relationships is a strong risk factor. (***).

Children with ADHD are at particularly high risk for internet addiction, with a strong association between addiction scale scores and ADHD severity scores. (****).  Depression, anxiety, and introversion are also risk factors.    Internet addiction is further associated with other addictive problems, including alcohol dependence and smoking. 

Another study looked at a rating scale called the IMQ-A,****** which assesses motives for using the internet.  The scale is based on the DMQ-R , which looks at a person's motives for drinking.   The highest risk for addiction is for those who are using the internet as a coping device (e.g. "to forget your worries"), while using it for social reasons or for education is less risky.

A recent review by Spada (******) suggests that the treatments thus far are quite straightforward:
 1) management of anxiety, depression, and ADHD symptoms
2) addressing family relationships if necessary
3) simply keeping track of internet use, and limiting it strictly
4) medication trials including antidepressants or stimulants if indicated.  Naltrexone 150 mg/d plus sertraline 100 mg/d was used effectively in one case. (*******).

I would add that basic lifestyle habits, including daily exercise, healthy diet, and a deliberate daily activity schedule (including social visits, work, and leisure), are essential, particularly since compulsive internet use leads to a lot of time spent alone in a sedentary posture. Postures in front of a device are also usually slumped, in a head-forward position, looking downwards.  Aside from physical health problems, this type of posture probably has negative psychological effects.  Standing and walking around regularly, with simple posture exercises, stretching in an extension position, etc. are bound to be useful.  Amy Cuddy's work on posture would be worth checking out--a good place to start would be her TED lectures. 

A few other points:
1) a bright screen should not be used near bedtime, since it will interfere with melatonin secretion, and cause sleep disruption.   An alternative for bedtime reading can be to use a device in which the font is reversed, with dim white letters on a black background. 
2) ironically, the internet can also be a valuable aid to treating psychological symptoms.  Web-based CBT can be nearly as effective as seeing a one-on-one counselor for some problems, and at the very least could be a valuable adjunct.   But the problems lie with spending too much time on-line, such that other aspects of life suffer.    Reward circuits in the brain may be fired up by numerous internet activities, in an exaggerated way, causing a distortion of judgment about the merits of continuing the activity. 

Ketamine for PTSD

Feder et al. (2014) published one of the first studies looking at possible use of ketamine to treat PTSD. * In this study, ketamine (0.5 mg/kg IV over 40 minutes) was compared with midazolam, on a randomized, double-blind basis, to treat PTSD patients.   In a crossover design, each patient was scheduled to receive a second infusion, 2 weeks later, of the drug they had not received the first time. 

I think a particular strength of this study was the use of midazolam as an active placebo.  The study would have been strengthened even further if they asked subjects afterwards to guess which medication they had received (most patients would have been familiar with benzodiazepines, and would have known that they did not lead to lasting improvements in their symptoms--presumably most of the patients would have wanted to receive the ketamine, as a novel, hopeful treatment).

The results appear similar to other studies of using ketamine to treat depression:  significant improvement in the week following the infusion.  The acute dissociative effects of the drug wear off completely within a few hours, as ketamine levels go down to zero during this time, yet the symptom improvements are maximal after 24 hours, and continue to be significant over a one-week period. 

The overall effect was to reduce PTSD and depression symptom scores at least by half, with improvements in all PTSD domains.

Side effects were not a major problem; in the 24 hours following the infusion, ketamine patients reported more blurry vision, restlessness, and nausea, compared to the midazolam patients.  Only one ketamine patient dropped out during the infusion, because he felt uncomfortable with it. 

For the patients who had received ketamine first, 7 of 22 were still responders after 2 weeks, compared to only 1 of the midazolam group. 

Once again, I think it would be useful for more studies to explore oral or sublingual ketamine dosing, since this would be much more convenient and practical for a larger number of patients.  A gradual intravenous infusion over 40 minutes leads to a fairly similar change in serum levels compared to GI absorption.  Rapid bolus dosing is an advantage of using IV, but this has not been used for administering ketamine to psychiatric patients.   There are differences in the ratio of ketamine vs. metabolites with the oral vs. IV routes, but I do not see that the differences are so great as to obstruct the benefits.   Dose finding is less precise with oral dosing, but this is a technical matter which can be simply resolved through careful titration.    In any case, science may answer this question for us, through well-designed trials.  A study design I would suggest for this would be a double-blind crossover study comparing oral ketamine + IV saline infusion   vs. IV ketamine + oral placebo, with one treatment per week for 4 weeks.  Doses could be adjusted according to response and side effects on treatments 2, 3, and 4.

Tuesday, December 30, 2014

Topiramate for Alcohol Use Disorders

Topiramate is an anticonvulsant which has shown some promise for treating a variety of psychiatric problems, including alcohol use disorders, binge eating, compulsive behaviour, and mood instability.  

One recent study, by Knapp et al, published in the February 2015 edition of The Journal of Clinical Psychopharmacology, compared topiramate with several other medications, and with placebo, for treating 85 heavy drinkers ("heavy" meaning over 35 drinks per week, for men).  * The study duration was 12 weeks.  The target dose of topiramate was 300 mg/day. 

Those in the topiramate group ended up having markedly fewer days of heavy drinking, markedly less total alcohol consumption, and reduced measures of craving, compared to placebo. In general, the topiramate group had at least twice as much improvement in these measures, compared to placebo, which was clinically very significant.  

This study was consistent with others, showing that topiramate can be an effective treatment for alcoholism.  **  

Cognitive-side effects (e.g. memory impairment)  are the main problem with topiramate.  So it is interesting to consider whether lower doses could be useful.  Martinotti et al (2014) did a small study showing topiramate 100 mg per day was useful for treating alcohol dependent patients, with a comparable effect size as the study quoted above.    ***

I am interested in topiramate for other problems which feature compulsive behaviour.  There is some promise in OCD, the studies showing mixed results.  In a genetic disorder called Prader-Willi syndrome, which is characterized by obesity, compulsive self-injury, and intellectual handicap, a trial of topiramate led to significant improvements in the compulsive self-injury.  ****   There have been several studies (e.g. *****) showing that topiramate can be of use in treating binge eating or bulimia, at doses similar to those described above.  Topiramate is also a leading preventative treatment for recurrent or chronic migraines, at a dose of 100 mg daily (******).  It is reasonable, then to think of topiramate in the many cases where there are a combination of these problems, for example a patient with recurrent migraines, who also may have binge eating symptoms, alcohol abuse symptoms, or compulsive self-injury. 


Meta-analysis is a powerful technique for summarizing data across many research studies.  For example, to understand the role of psychotherapy or antidepressants to treat depression, a meta-analytic study could give us our best starting point to estimate the effect size.

But the meta-analytic method has a prominent weakness, what I would call dilution:

Suppose that one is doing a meta-analysis of the effectiveness of surgery vs. supportive care for treating abdominal pain.   Many studies might show that surgery is remarkably effective, yet others would show no difference, or even a negative effect, compared to supportive care.  The meta-analysis could average these out, and conclude that there was little difference.    The reason for the dilution is that there are some specific types of abdominal pain, with specific causes, which are best treated surgically (e.g. appendicitis).    Many other types of abdominal pain settle down on their own, or require simple supportive measures.  In the past, it was often difficult to determine whether a patient definitely had appendicitis or not, in the early stages of the illness.   Therefore there would have been many unnecessary appendectomies, and many other cases of ruptured appendicitis operated on too late.

Similarly, in psychiatry, I think it is probably true that there are particular subtypes of depression (or other diagnoses), which respond much better to psychotherapy, or much better to a particular medication, or which might settle down completely on their own with no help at all.   At present, our diagnostic schemes do not help us very much to differentiate between these groups.  We often assume that mild depressions are best treated with psychotherapy, and severe depressions are more likely to need medication treatments.  While there is evidence that supports this assumption, it is not invariably true:  some cases of mild depression persist for long periods of time, do not improve with psychotherapy, but may improve dramatically with a medication trial.  Conversely, some severe cases of depression may not respond well to medications, but improve dramatically with psychotherapy (sometimes a very particular type of psychotherapy).

An ongoing area of research must be to improve our ability to predict the optimal treatment strategy.  I suspect that in most cases, this strategy will involve some combination of psychotherapy, medication, and practical social support.    I think that the science to help us in this task is more likely to come from genetics, and less likely to come from more sophisticated questionnaires or symptom scales.

The search for these answers is confounded, in psychiatry, by a very high risk of placebo-like psychological effects, which must be addressed by studies which have very careful placebo controls and active placebo controls.

For example, many patients are understandably attracted by a very "high-tech" or "advanced science" approach to treating their illness.  So we have some clinics which offer sophisticated technology, such as neurofeedback, PET imaging, genomic analysis, etc.  While these technologies are interesting, and possibly very useful, they also carry a sort of "guru effect."  A PET scan yielding exciting images showing metabolic changes in the brain, accompanied by a detailed diagnostic report, could be much more persuasive than reading the exact same report without the images.    Therefore the PET imaging could act as a marketing tool, to cause the person to take the report more seriously, irrespective of whether the imaging actually shows something of true scientific relevance.  It would be like visiting a fortune-teller, but receiving actual images of your brain which are referred to in the fortune-teller's predictions about you.   It would be especially convincing!    Similarly, with neurofeedback, the dazzle of the technology could cause people to take the therapeutic tasks more seriously, causing improvement separate from the independent benefit of the technique.   I am particularly concerned about the risk of bias with these techniques, because some clinics or private practitioners are charging very high fees for patients to have them.  This is an environment in which selective glowing testimonial accounts could distort a reasonable summary of the data.

In order to conduct research properly with these new modalities, we must have very careful active placebo groups.  In a neurofeedback study, for example, there should be sham neurofeedback which generates a similar type of interactive therapeutic task, with a similar degree of technological dazzle. 

Wednesday, December 17, 2014

Intensive vs. Regular CBT for PTSD

Ehlers et al. published a good study in the March 2014 edition of The American Journal of Psychiatry in which they compared the following treatments for PTSD:
1) 3 months of regular weekly CBT
2) 7 days in a row of intensive CBT (up to 2 hours daily)
3) 3 months of weekly supportive therapy
4)  waiting list control

They found similar good treatment results, after 40 weeks of follow-up, in the regular CBT and the intensive CBT groups, with a slight edge for better response in the regular CBT group.  Total remission in symptoms occurred in 50-70% of these groups, compared to only 30% in the supportive therapy group, and no change in the waiting list group.

Once again, a weakness in these CBT studies is a failure to account for the amount and quality of homework done.  Possibly the regular CBT group had more frequent reminders to keep up with homework tasks and exposure activities, which is a reason why they did slightly better than the intensive CBT subjects. 

What I take from this study is, first of all, CBT techniques (or related techniques which involve similar practice and exposure) are imperative, regardless of other supportive techniques also used. 

Second, I think there is a role for both intensive CBT and longer-term weekly CBT.  It could be useful to have a regular course of CBT with at least one week of intense weekly sessions as well.  It reminds me of any other skill to learn, such as learning a foreign language, learning to swim, learning a musical instrument, etc. :  regular lessons are great, but an intensive week-long program could give you a huge boost, in terms of skills, habit-building, and interested devotion to the work.  In both of these cases, much of the progress will be a result of diligent daily practice and homework, over a period of months. 

Topiramate treats alcoholism in those with a particular genotype

Kranzler et al, in the April 2014 edition of The American Journal of Psychiatry, show that topiramate 200 mg daily led to very substantial reduction in alcohol use in heavy drinkers, compared to placebo.  But this effect was dramatically present only for a subgroup of drinkers who have the  CC genotype of the rs2832407 gene.  This genotype is carried by about 42% of people having European ancestry. 

Topiramate stands out as a very reasonable, safe, and relatively well-tolerated adjunct in the treatment of alcoholism.  I don't think it is necessary to test for the genotype--it would be reasonable to offer an empirical trial, and to predict with the patient that there will be about a 40% chance of the medication having a dramatic effect.  If it doesn't help, the risks would be minimal.  Since topiramate is an anticonvulsant, it could theoretically treat or prevent withdrawal symptoms, even if it doesn't independently reduce the urge to drink. 

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.

Wednesday, August 20, 2014

The Better Angels of Our Nature: Why Violence Has Declined, by Steven Pinker: A Book Review, Part 3

So, in conclusion, Pinker's book is very important and can be broadly applied not only to understanding and working towards continued reductions in violence, but these ideas can be useful in developing healthier psychological strategies in daily life.

These principles include:

1) continued education, to bolster reason, cross-cultural understanding, communication skills, empathy, historical knowledge, and even economics and statistics (these latter subjects can help combat cognitive biases which impede clear understanding of information pertaining to daily living)

2) foster trade instead of fostering war.  In some recent news examples, this may not be reasonable (e.g. with some extremely violent groups), but at the very least, fostering trade with adjacent communities would be useful to form alliances. 

3) exercise and strive for freedom of speech

4) expand our circles of empathy, to include those in other groups, cultures, and situations.  Ultimately, a global issue is to include the environment itself in our circle of empathy.  In depressive states, one may be directing aggressive thoughts or actions towards oneself.  So the circle of empathy should deliberately also focus on including oneself.

5) be aware of cognitive biases, such as overconfidence in the setting of conflict, underestimation of the risks of conflict, the tendency to deliver vengeful retaliations that would be considered excessive by a neutral observer, and to overestimate the malevolence of an opponent's motives.    This could be applied to an analysis about one's own depressive thoughts about oneself.

6) avail oneself of mediators or peacekeepers (this can be a role of a therapist).

7) move away from authoritarian or tribalist practices or beliefs, and instead focus on inclusiveness, individual rights, and fairness.  For those involved in religion, work toward a more inclusive, peacemaking, ecumenical, humble theology, with room to include modern scientific findings pertinent to morality, fairness, cultural understanding, and justice. 

8) strive for dignity rather than honour

9) work on ways to improve self-control.  This does not mean a renunciation of Dionysian enjoyments, but rather it means never allowing one's impulses or habits or enjoyments to cause harm or to rule one's life.

The Better Angels of Our Nature: Why Violence Has Declined, by Steven Pinker: A Book Review, Part 2

The first section of Pinker's book is an exhaustive review of violence rates throughout history.  This even includes looking beyond our own species, to other great apes, to understand aggression in our evolutionary lineage.  He also reviews cultural attitudes towards violence throughout the ages, as manifest in literature and the arts, and also in accounts of daily social and entertainment practices.  It is very disconcerting to learn about the extent to which horrifying acts of cruelty were commonly accepted, or even considered amusements (the events in the Roman Colosseum comprise just one of many, many examples)

Clearly, rates of violence were much, much higher in all previous periods of history.  Today the risk of suffering a violent non-suicidal death (from war or other crimes) is in the order of 1% or less (this is the total risk over an entire lifespan).    In most prosperous areas of the world it is much less than 1%.  Of the 245 000 deaths in Canada in 2012, 543 were due to homicide (0.2 % of the total).link   link2

But in all previous eras of human and pre-human history, these risks were orders of magnitude higher,  according to a variety of streams of evidence which Pinker amasses.  Instead of 0.2%, the rates were 10% or more.    If anything, much of this data may actually underestimate these past rates, since violence was so much a norm in previous periods of history that many violent deaths or even massacres were barely mentioned in historical texts.  Risks of non-homicidal violence were much higher still, such that most everyone in the population would have been traumatized in some way, or would have had a close friend or family member who was severely traumatized. 

Pinker outlines various of the forces which have driven violent behaviour over the ages; here are some of them:

1) predation
2) dominance
3) revenge
4) communalism/tribalism/nationalism
5) sadism
6) isolation
7) authoritarianism
8) ideology
9) lack of intelligence

Predation is described as a simple goal-oriented motive, such as robbery or looting.  Yet this strategy is "zero sum" or "negative sum" in that there is no net gain during a robbery, only a transfer of property, and most likely a destruction of the means to efficiently produce more property (e.g. jewelry may be stolen in an attack, but the infrastructure or morale needed to produce more or better jewelry gets damaged in the process).

With societal evolution, free trade becomes a non-violent alternative to predation, which allows the process to be "positive sum."   In this case, goods could be traded for jewelry, leading to a prospering group of jewelers who can then produce more or better jewelry in the future.  Both parties gain.   In order for free trade to occur, and the ensuing reduction in predatory violence, there must be improved communication, a fairly governed commercial system, and penalties for predation which are agreed upon by both parties.

In a psychotherapeutic milieu, this principle could lead to the idea of improving communication and stable transactional rules between potentially conflicted individuals.  In general, the idea of trading with your enemy instead of fighting your enemy may not naturally occur to people.

Pinker does not adequately discuss some of the problems with trading relationships, and of free-market economics in general.  Such relationships can be imbalanced, exploitative on some level (either directly towards the individuals or nations involved, or towards the environment), or favouring a relatively small elite while having little benefit for the majority.  I think there needs to be more emphasis on "fair" trade, including a strong focus on environmental issues.  This is consistent with Pinker's observations about the need to expand a "circle of empathy."  This circle should expand to include not just trading partners, but the larger communities affected by trade, and the benefits or consequences to the natural environment.  Trade may often benefit the environment, through a simple economic efficiency argument:  the lowest-cost economic solution to a problem is favoured by free trade, which in turn can maximize the available eonomic resources to protect the environment.  But in order for this efficiency to be protective, there needs to be structured safeguards in place to prevent social or environmental exploitation. Another big issue I have found with conventional economic theory is that costs are underestimated (such as long-term environmental damage), and the cross-sectional cost appears to be very low; often those involved are not held responsible for the ultimate long-term costs.  In any case, this inaccuracy in measuring costs distorts the system, and causes it to be short-sighted.  

Dominance contests can be seen in many species, often as part of a competition for mates.  Most often, of course, these are behaviours seen in males.  In humans, this can give rises to meaningless displays of strength or machismo, with an associated culture of "honour" in which small perceived slights can result in excessive aggressive reactions. Associated psychological phenomena include overconfidence, underestimation of the losses associated with the conflict, and of course lack of empathy for the opponent. In celebrating a culture of "glory and honour" there can be an utter disregard for the individuals and families affected by the ensuing violent losses.

If this type of behaviour is selected for in the population, it gives rise to large, aggressive, arrogant, reckless males who are easily provoked.  In other species it can give rise to males having harems with multiple mates, while driving away or killing other male challengers  (we see literal examples of this in human groups throughout history). 

In humans, this type of dynamic can occur in "honour-based" cultures; previous periods of history often featured distinguished gentlemen absurdly fighting to the death in duels, often over trivial conflicts.  But entire nations can behave in this fashion as well.

Improvement in this type of problem comes with greater education, strong emphasis on women's rights and gender equality, and selection pressure:  reckless, aggressive males with poor impulse control are much less likely to be found attractive as mates in the modern era!   Instead, most elements of modern culture favour self-control and a culture of "dignity."  It is no longer cool or attractive to be a bully or a hothead. 

Revenge is an understandable reflexive process, and it is pointed out that some degree of revenge can be a deterrent to subsequent violence (to show no revenge can invite subsequent exploitation).  The problem with revenge, as Pinker shows, is twofold:  first, wronged individuals or states tend to want to deliver more punitive harm than a neutral mediator would prescribe.  The individuals doing the wrong likewise tend to underestimate their culpability or guilt (e.g. a great many convicted felons may have a smaller estimation of the magnitude of their guilt or responsibility for harm than a neutral observer or their victims would conclude).  This leads to a cycle of revenge, in which each group retaliates vindictively against each other, with force that is often out of proportion to the offense, and each wrongdoer underestimates their culpability.   The retaliation is itself therefore felt as an assault by the recipient, rather than as a fair punishment.  The violence therefore continues in an escalating fashion, with each group feeling justified in their actions, egregiously wronged by the other, and with each group inducing future acts of vengeance from their enemies.

The solutions to this predicament include having neutral arbiters--a fair system of policing and justice, empowered by a neutral and fair government which has a motive of minimizing overall harm in its citizens.

On a psychological level, a solution is to recognize the cognitive biases which lead to excessive retaliations and excessive justifications for one's own excesses.  Another solution is to recognize the need for neutral mediation to help resolve ongoing conflicts.

Communalism, tribalism, or nationalism are understandable, common human experiences.  Early human culture required a cohesive sense of protecting one's fellow villagers from attacks from neighbours.  Yet, tribalism fosters patterns of revenge, predation, and dominance-based aggression on a group level.  Having separate tribal cultures, often with language and geographic barriers, is a barrier to empathy for outsiders, particularly if a cycle of warfare has already begun.  We see this type of aggression on a large and small scale, all around us.  In some cases it is playful, as in sports teams from different communities.  Gang behaviour in large cities has a tribal quality, with battles over control, protection, predation of resources, and "honour."   But entire nations behave this way.  We subjectively have an urge to enjoy national identity, but we have to be wary of the violent associations of this mindset.

An approach to this issue is to expand our "circle of empathy," and to view those from other groups as partners rather than enemies.   I suspect the healthiest vestige of nationalism that we can safely keep is to have sports teams.  I think this is also a reason to support free, fair international trade.  Protectionist policies must be based on a notion that there is an "us" and a "them".  But it is fair to view everyone in the world as part of "us" at this point.

Nationalist conflict is one of the most devastating factors causing worldwide violent death and suffering through the ages.

It is for this reason that I support the idea of having international sports events -- I believe that this is a symbolic peaceful sublimation of nationalistic conflict, transforming this type of tension into a playful harmless talent show.   The economic indulgence of such events, such as the Olympics, is an understandable complaint, but I think the pursuit of such playful, peaceful activities is very important.

Sadism  may seem like a rarity, relevant only to extreme cases.  But smaller forms of this issue can occur in communities or in one's inner life.  The driving force in sadism is addictive:  repeated behaviours, even if extremely harmful, can lose their aversive or "taboo" character through repetition, and even lead to addictive pleasure, associated with excitement, relief of tension, etc.  This phenomenon can occur in personalities which had previously been quite "normal."    Pinker does point out the likelihood that psychopathic personality--a pathological lack of sympathy for others-- is a risk factor for sadistic behaviour, and that those with this type of personality are more likely to be attracted to occupations in which they could indulge their violent predilections.  In the book, he does not address the environmental or social causes of psychopathy, though alludes to this problem being at least to some degree a neurobiological variant with heritable aspects, and not entirely due to environmental adversity.  In any case, not all psychopaths end up becoming violent sadists, and not all sadists are psychopaths. 

 In depressive states, various forms of physical and figurative self-injury can become sources of relief, and lead to an escalating pattern of violence against self.   This is not "sadism" but it could be considered as arising similarly, as an addictive habit to which the person becomes tolerant and desensitized, leading to a craving for more and more highly destructive behaviour. 

A solution to this issue is to focus on prevention, and to recognize and avoid risk factors.  In a police or military setting, for example, it needs to be recognized that maltreatment of hostile prisoners can occur and escalate through this process.  Abuses of this kind are not some kind of bizarre perversion, but stem from failure to include judicial safeguards adequately to prevent the police or prison guards from getting involved in an addictive habit of maltreating others.  This can be challenging, because many of the prisoners may have behaved in a terrible way themselves (e.g. violent criminals) and so the initial aggressive responses to them may be approved by everyone involved.

In a personal setting, prevention is also important.  Self-injury often begins secretively, without the addictive risks being appreciated, and by the time the problem surfaces to others, it has become an entrenched habit.  At this stage, approaching it as a potentially lifelong addictive risk becomes necessary, with a variety of psychotherapeutic strategies employed.  For those who engage in sadistic behaviour towards others, I think society should be equipped to approach them as permanent risks to others' safety.   This does not necessarily mean longer prison terms, etc. (though this may be necessary in some instances) but I think it does at least mean longer-term societal scrutiny for protection of others.  

Isolation is a risk factor for violence due to a tendency to form a stronger ingroup, view outsiders as a threat, lack the communication or language to resolve disputes peacefully with outsiders, and to lack the advanced education that could bolster diplomacy, empathy, or self-control.

During early human history, groups existed in relative isolation from each other.  Today, groups which are more geographically isolated (e.g. in remote mountainous areas) tend to have much higher rates of violence, as well as less education.  With the advent of modern communication and transportation technology, isolation on this level does not ever have to be as absolute as it has been in the past.  Yet, some groups may deliberately foster isolation, even when they live in large cities.  I think it is important to foster widespread community interactions between isolated groups.  

On a personal level, isolation is likely to magnify suspicion towards strangers, leading to exaggerated negative reactions to others' behaviour.

Psychologically, problems with isolation may be due to social anxiety, depression, or psychotic paraoia, but the isolation itself becomes part of the vicious cycle of symptom exacerbation.

Every person or community may have a certain "set point" for healthy engagement with others, e.g. some people are more comfortably gregarious than others, but I think some type of social practice and engagement is necessary for the health of individuals and communities. 

On a practical level, learning to speak other languages and customs lessens the isolative boundaries between people.  As a strategy of personal development, it could therefore be healthy to learn other languages, to travel to different countries, and to experience and learn respectfully about other cultures.  Treatment of underlying symptoms, such as paranoia or social phobia, can of course be important. 

Authoritarianism evolves naturally from the most ancient origins:  stronger members of a group will dominate and assume leadership powers.  This factor fits closely with the ideological dynamics of aggression.  Those who challenge the authoritarian leadership can be subject to severe aggression.  One of the perpetuating factors for this dynamic includes the cognitive illusion that everyone supports the authoritarian leader or the authoritarian principles.  Even those who quietly dissent may be so fearful of reprisal that they will act to support the leader, and even punish other dissenters to prove it.  An analogous cognitive distortion is the belief among college students that the majority of their peers enjoy binge drinking--this belief normalizes such behaviour, and causes more people to engage in it because they erroneously thought it was an accepted norm.

A protection against this dynamic is fostering a politically open democracy with freedom of speech.  On a personal level, I think it is healthy and protective to question authority as an intellectual norm.  This includes not only teachers and professors, but also religious teachings.  Authoritarianism that is couched in religious dogma can seem so "sacred" that challenging it would seem disrespectful or like a taboo, thus leading to terrible unchecked excesses and distortions justifying violence or other harms and suppressing intellectual growth.

I had assumed that there would be a universal affirmation of the desirability of multi-party democracy throughout the world.  Yet, I have recently been looking at the PewResearch Global Attitudes Project surveys, including a poll done in 2009 (well before the recent conflicts in Russia and Ukraine).  (link)

This survey shows that people in Russia and several former Eastern-Bloc countries such as Hungary, have had a huge reduction in their enchantment with the idea of democratic government, beginning long before the recent conflicts.   Ukrainians gave some of the lowest ratings of all, regarding attitudes towards democracy, freedom of speech, etc.    I suspect that a major reason for this has been that the democratic changes in these countries have been laden with a lot of corruption, instability, and economic problems.

This is reminiscent of what Pinker described in post-colonial African states, which experienced a large surge in violence rates after declaring independence.  This does not at all mean that colonialism was "good," but rather that the benefits of democracy and societal freedom can only come after a state has become stable in terms of economy and political organization.   The period after major political upheavals can be relatively anarchic, and economically harsh, leading to a steep decline in morale for the population. 

Ideology can lead to extreme violence, through offering a cohesive set of beliefs which bind an ingroup harmoniously, often with a utopian goal, leading to a rationalization to destroy outgroups. Utopian goals can sound attractive, but often the enactment of these goals involve suspension of the other elements of societal growth and non-violence, such as fairness, justice, empathy for outgroup memebers, etc.  Those who commit catastrophic acts of violence within an ideological framework may understand their actions to be normal or just, and may easily dismiss complaints that their actions are wrong.     Our recent history is full of examples of this type, including Nazi Germany.

Unfortunately, there are many examples in history of religious ideologies leading to extreme violence in this way, continuing with examples in today's news.

A prevention for this type of problem includes education, including in the arts and humanities, a commitment to ecumenical approaches in theology (regardless of one's religious orientation), and a commitment to have diplomatic relationships with those having different ideological viewpoints.

I think these preventions apply on a large scale in societies, but also on a personal, individual level.

Intelligence, the greatest talent of humankind, has the power to defuse conflict through negotiation, wise strategizing, and improved empathic understanding of one's opponents.    Cognitive biases are not eliminated by intelligence alone (as Kahneman has shown), but the capacity to employ reason rather than rage to solve problems is enhanced by intellectual training.  Such intelligence has grown over the generations, as Pinker has shown.  This is likely due to better education, and exposure to a more stimulating global cultural milieu.  Unfortunately, many in the world lack access to the basic resources or freedoms to develop their intellect in this way.  Part of global peacemaking must therefore include a strong emphasis on universal access to education.

Intelligence, of course, also permits a higher chance for employment, prosperity, and diverse leisure activities, all of which reduce risks for violence and other harms.

On a more immediate, personal level, intellectual development could be framed as a component of psychotherapy.  This could work not only as a way to focus the brain on activities apart from depressive rumination, but also could strengthen faculties of the mind which could act as skilled "negotiators" to calm the self-injurious impulses which can occur in depression or anxiety.  Some of the CBT literature shows that this type of therapy works better in those who are more highly educated.  Conversely, I suspect that better education and intellectual training can make psychotherapy work better.

Tuesday, August 19, 2014

The Better Angels of Our Nature: Why Violence Has Declined, by Steven Pinker: A Book Review, Part 1

I have just finished Steven Pinker's book, The Better Angels of Our Nature: Why Violence Has Declined

I think it is a masterpiece of scholarship and research, combining the fields of psychology, history, political science, anthropology, economics, and statistics to contribute a hopeful affirmation about the progress the world has made to reduce violence and to improve quality of life.

My favourite scholarship is the type which combines multiple fields in this way!  

In these posts I would like to briefly summarize the book, and to reflect about ways to apply some of Pinker's insights to the practice of psychotherapy.

I see there has been mostly strong praise for this book among critics, but predictably there has been some controversy.    Cultural groups which still have strong authoritarian, communal, tribal, sexist, or fundamentalist values may find some of Pinker's conclusions to be critical of their way of life.  Mind you, he does show that in almost all such subcultures, such as conservative groups in the U.S., there have been positive changes, for example towards affirming rights for previously disenfranchised groups.  It is just that these changes usually lag a decade or two behind such changes in the rest of the population.  An attitude about women's rights or gay rights that would have been called "liberal" in 1970 would be considered a norm in many conservative groups today. 

Pinker shows that most elements of religious belief and practice have had negative impacts on rates of violence and war, due in part to causing an ingroup mindset, which tends to undervalue the human worth of non-believers, therefore facilitating maltreatment of those with a different faith.    Also most religions have a type of authoritarian structure, including about the concept of divinity itself.  The notion of an afterlife can not only model infinite punishment ("hell") as a supposedly fair possibility for an individual based on offenses such as "disbelief" but could encourage such an attitude of infinite punishments in approaching other individuals or cultures.  Conversely, with infinite reward ("heaven") in the picture, perhaps with simple criteria such as "belief" to be the ticket of entry, this could be experienced as a license to engage in many destructive acts during life while minimizing the relative value of earthly justice.

Other critics question his statistics, but here I think he has been very impressively thorough.  His statistics do not at all imply that violence has miraculously disappeared in modernity, and very clearly do not imply that the most horrific possibilities of violence -- such as the scale of events which happened in World War II -- cannot happen again.  In fact, his discussion of statistical power-law distributions modeling violent conflict gives rise to great concern:  based on this distribution, one can expect an arbitrarily large and devastating conflict to occur in the future, since this type of distribution is "tail heavy" statistically.  His analysis does give reason to be hopeful, though--the underlying causations and probabilities which become the parameters of these statistical patterns are themselves declining.

An example of a power-law distribution is the length of words that would be generated on a typewriter if one were to type on the keys and the spacebar randomly.  Typing the spacebar would separate individual words.   The length of the word would represent the magnitude of  (or loss of life from) a violent conflict. With this analogy, a conflict happens every time the spacebar is pressed. One could see that short, small conflicts would be most common, but that longer, larger conflicts could happen periodically, though less frequently, in a random pattern.  It is disconcerting that this type of distribution can have an infinite expected value, representing total destruction of the population.  As we know, this is actually a possibility in the nuclear age.

But Pinker's thesis also shows that the parameters of this imaginary typewriter are changing--with time, the typewriter is gaining more and more keys (just like Microsoft keyboards!).  This causes the relative risk of pressing the spacebar to gradually decrease with time   Also, metaphorically, Pinker is showing that the information content of each key is increasing, so to speak, causing fewer keys to need to be pressed at all.    Just as with computer keyboards, we are even developing ways to interact without using keyboards at all (e.g. with mice, or voice commands).  The mechanisms he shows for these changes in risk parameters are increased education, intelligence, an expanding circle of empathy, an expanding force of reason, improved human rights (e.g. for women, racial minorities, and people having different sexual orientations), free and fair trade,  and improved stable government (what he calls the "leviathan").

Thursday, April 3, 2014

Deep Pressure Stimulation for anxiety, ADHD, insomnia, or autism

Someone was telling me last week about a snug sweater that is available for your pet dog or cat, which is intended to soothe anxiety or phobic behaviour!  Here is an informational site for a business selling this:
The whole idea made me smile!   Maybe it’s gimmicky, but what if there’s something to this?

I think the idea is very simple, that pleasant, hug-like tactile stimuli can be emotionally comforting.  As with other sensory stimulus treatments for mental health symptoms, why not try tactile things?  We have, for example, bright light therapy, calming audio recordings, and aromatherapy, each of which have a reasonable evidence base.  Of course, there is massage therapy, but usually this would consist of  brief, fairly expensive sessions which would rarely be practical to arrange daily or continuously.  
Here are the results of my survey of this issue:
For children with autism or attention problems, there are weighted compression vests available on the market, which are supposed to help cognition, comfort, and behaviour.  These are simply vests which weigh about 10% of body weight:   This 2014 study in an occupational therapy journal showed significant improvement in ADHD symptoms in 110 children, average age 9 years.  The study had a randomized, crossover design, with subjects putting on the vest and immediately doing a CPT test.  The subjects were scored according to the CPT test result, and according to observations of behaviour during the trial.   Symptom improvement attributable to the vest was quite significant: about 20% improvement in being on-task, 50% reduction in fidgeting, and 20% reduction in CPT omission errors.  In this study, the 4 weighted vest subjects had 18-25 % improvement in on-task behaviour, also 3 of the 4 children asked to wear it more!  In this review article, they found insufficient evidence to recommend weighted vests. But most of the studies reviewed were looking at very young children (under 5) with autism.  It is of greater interest to me to look at the use of this strategy for older children and adults with anxiety or attention problems. 

This study showed that swaddling babies reduces the pain response to a blood test needle, compared to control.  
Temple Grandin is a famous autistic woman, with a BA in psychology and a PhD in animal science, who has been very open about her personal history; she has become an authority in the area of providing safe, ethical care and comfort to agricultural animals.    These are links to Grandin’s 1992 paper in Journal of Child and Adolescent Psychopharmacology in which she describes her own very beneficial experience of a device she built (“the squeeze machine”) which she used daily for many years.
She found this machine to be comforting, and to even improve her subsequent ability to tolerate other types of sensory and interpersonal stimuli as an adult.

Here is a very recent article with Grandin as co-author:  This is a case study of a woman with bipolar disorder who reported some benefit from deep pressure techniques.  Other adjuncts in this case were use of a squeeze ball, chewing gum, lightly tinted glasses, and a soft brush to rub against the skin. I'm a bit surprised this got published, though, since it seems they didn't really use any one technique systematically. 

Weighted blankets are another idea along these lines.  Here is a website selling items like this:   I see the weights are up to 20 pounds for a larger blanket, again with a recommendation of about 10% body weight.    It seems like a home-made version of this wouldn’t be too hard to make, or at least to experiment with.  The material used for the extra weight is often simply small, smooth stones.  
Sleeping in a mummy bag (a type of sleeping bag used for camping) is another similar idea.   

So, in summary, deep pressure stimuli of this sort could be worth a try to treat ADHD, anxiety, insomnia, or tactile hypersensitivity, with very little risk.  I suspect one could get an idea of results and tolerability quite quickly.  A key idea, that Grandin emphasizes, is that the stimulus should always be fully under your control, so it would be useful I think to be able to adjust the weight, and to remove it very easily. 

Tuesday, March 11, 2014

The obsolescence of paper journals and conferences

I was reading an editorial article the other day, entitled "A word to the wise about ketamine" by Alan Schatzberg (American Journal of Psychiatry, March 1, 2014).  

The article is a brief opinion piece cautioning psychiatrists about the use of ketamine as an antidepressant.  It includes such statements as this:
Without more data on what ketamine can do clinically, except to produce brief euphoriant effects after acute administration, and knowing it can be a drug of abuse, it is difficult to argue that patients should receive an acute trial of ketamine for refractory depression.
Of course, this is an important opinion, a valid point of debate!  If something like ketamine is indeed simply giving people a momentary high, then leading them into a dark pathway of addiction, then we need to acknowledge this risk and sound the warning!

The problem I have with this editorial is the nature of the debate that can take place in response to it.
Each statement in the editorial can be challenged in quite an engaging debate, for example:

 -benzodiazepines, antihistamines, opiates, and even antipsychotics such as Seroquel, are drugs of abuse as well, yet they have well-established medical benefits in many instances, independent of their "brief euphoriant effects."

-severe refractory depression which has not improved with multiple conventional treatments is a devastating condition; it does not seem "difficult to argue" at all, in favour of a simple agent administered weekly, in an office setting, with a drug level of zero shortly after the patient leaves the clinic, and which can produce profound relief and improved function lasting for a week at a time in a significant number of people.

-medications with potentially dangerous long-term side-effects, including lithium and antipsychotics, are routinely prescribed for refractory depression, often one after the other, even when previous similar trials have not helped at all!  An argument could be made that it should be time to stop this repetitive medication loading, after a dozen or more previous similar trials have done nothing except cause side effects!   It is interesting to consider the adverse consequences, psychologically and medically, of repeated ineffective psychotropic medication trials. 

Now, with this response I do not claim that ketamine is some kind of miracle drug.  I think it is promising, and deserves careful consideration.  It is entirely possible (probable, even) that there are risks associated with it that are not well-enough appreciated.  But in a refractory depressed population, the risks of continued symptoms are devastating!

I also do not mean to put down the value of other conventional medical therapies.  Lithium or antipsychotics or multiple conventional antidepressants may indeed be important, valuable, life-saving treatments, and I think we must keep an open mind about trying them, especially if they have not yet been tried in particular patients.  

Back to my main point, though, which is a process-related point:

-editorial writers in a major journal carry a lot of persuasive weight, which is certainly enhanced further by the editor's long list of publications and awards.   But when it comes to making decisions, it is ineffective to simply hear one person's opinion, even if that person is the leading expert in the world!  --especially, I might add, when this opinion comes from a position of obvious bias (for example, towards theoretical conservatism, lack of personal experience with the specific subject matter,  or "expert" status which is based on expertise in other subject areas than the issue at hand).   Every opinion should be heard, of course!  But in order for a productive understanding of an issue to take place, there needs to be debate!

In a journal such as The American Journal of Psychiatry one could certainly engage in a debate, for example by writing a letter in response to an article.  But, first of all, there is a huge time lag involved!  It could be a month or more before any response would be seen.  Even if the response was published, it would be located in the letter section, rather than in the prominent editorial section.  And imagine having a debate with someone professionally, but in a framework in which you could only exchange comments once per month!  I think the quality of the debate would suffer!  And I suspect many observers of such a debate would lose interest! 

We live in an era where it is possible to engage in an instantaneous debate online.  We can do this on most news websites.   Of course, on news sites, etc. a lot of the public commentary features quite extreme opinions, trolling, etc.  But in a professional on-line publication it would be quite easy to limit comments or discussion only to members of the psychiatric community.

It seems a puzzling and unnecessary relic at this point to observe an editorial of this sort, an opinion piece which has a great deal of room for discussion, but where no discussion can take place in a timely manner.  

There are several other reasons why paper journals in the sciences are obsolete:  first, they are a waste of paper!  Second, many advanced techniques of data presentation (for example, see Hans Rosling's work with health statistics) require a computer to be visualized.  A static 2-dimensional graph or photograph on paper conveys only a tiny fraction of the information which could be easily displayed online.  Similarly, I believe the entire data set should always be provided for any published study, so that the reader can conduct an independent analysis of the data.  This further reduces the possibility of bias in presentation, and conversely increases the possibility that another person could see something in the raw data that was missed by the authors!  Third, if one reads scientific papers online, one can instantly look at hyperlinked references to get a much richer and deeper understanding of the paper (including the paper's strengths and weaknesses). 

For many of the same reasons, I think lectures at professional conferences and meetings are obsolete as well, as least in their role as educational loci!  A professional conference may be a good place for social connections, networking, and tourism, or perhaps to attend a workshop to acquire a new hands-on skill, but it is wildly inefficient as a primary source of didactic education!  This is true for many of the same reasons described above for journals:  lectures are much more likely to be condensed opinion pieces on the part of the lecturer, usually without a lot of room for rich intellectual debate.   And another problem with conferences, in terms of persuasion and bias, is that they are designed to be luxurious!  If the experience of learning a possibly controversial or an outdated dogmatic idea takes place during a time which is simultaneously considered a vacation, in fancy hotels, with gourmet meals, in an exotic location, there is a much higher risk of biased persuasion taking place.   Didactic education does not require physical travel, it requires intellectual travel!

Friday, January 24, 2014

Tryptophan Depletion studies

The best review of tryptophan-depletion studies is by Moore et al. (2000).

 I think it is an accepted part of clinical psychiatric theory that serotonin obviously is related to mood, and the more serotonin there is, the better mood must be, and the less serotonin there is, the worse mood must be!  

With tryptophan-depletion, subjects are given a drink which results in a radical reduction in serotonin synthesis within hours.  It is strongly believed, though not rigorously proven, due to technical limitations, that such depletion results in a reduction of serotonin release by serotonergic neurons in the brain. 

The main consistent finding of these studies is that depressed patients who are treated with a serotonergic antidepressant, such as an SSRI, but who have not yet recovered fully from their depressive episode, are very sensitive to a sudden worsening in their depressive symptoms immediately after tryptophan-depletion. 

But, fully remitted patients tend not to have any depressive relapse following tryptophan depletion!

And depressed patients who have not yet received any antidepressant tend not to have worsening depressive symptoms following tryptophan depletion! 

And depressed patients treated with non-serotonergic antidepressants (such as desipramine) do not have worsened depressive symptoms following tryptophan depletion! 

There is little evidence that tryptophan depletion consistently affects panic or OCD symptoms. 

One study quoted in this review, by Delgado (1991), showed that in a group of untreated depressed patients given tryptophan-depletion, 37% actually improved following depletion, compared to 23% who got worse (by 10 points on the HDRS). 

It is obvious that momentary tryptophan depletion, and the resulting drop in serotonin synthesis, does not have consistent effects on psychiatric symptoms.  The effect is only reliable in partially treated patients taking SSRI's.  It may be that in these patients, it is a sudden induction of a withdrawal-like state which causes the sudden symptom change.  Or, it could be that in these patients in an early state of recovery, there is a temporary dependence on serotonin levels, which are working to "push"the patients towards recovery.  The tryptophan depletion suddenly removes the source of this "push", causing sudden relapse.  But serotonin clearly must not be the only possible way to "push"towards recovery, because depleting serotonin only has a negative effect on patients beginning SSRI treatment.