Thursday, June 10, 2010

Naturalistic study comparing quetiapine, ziprasidone, olanzapine, and risperidone

This study caught my eye recently (here's a link to the abstract:)

It's a naturalistic study, published in BMC Psychiatry in 2010, prospectively following 213 patients with symptoms of psychosis, who were randomized to receive one of four antipsychotic medications (quetiapine, ziprasidone, olanzapine, or risperidone), then apparently followed for up to 2 years.  

My prediction with such a study would be that all four medications would have similar effectiveness, with a slight edge in favour of olanzapine.

In fact, the results showed a slight edge in favour of quetiapine.  There were no substantial differences in tolerability.

The problems with this study, though, include the following:

1) Most of the data was actually for patients who had only been followed up for 6 weeks (not 2 years!).  Only 8 of the 213 patients were followed up for 2 years.  Of these 8, 5 were taking olanzapine, 2 were taking ziprasidone, and 1 was taking risperidone.  Perhaps one might be tempted to conclude that olanzapine is the drug that has the highest chance of being acceptable for long-term use.

 2) The results were presented in a type of "refined" fashion, for example the changes in symptom scores for each drug over time were presented as graphs with a single straight line for each drug, plotted over a 300-day period.  This type of graph omits a tremendous amount of relevant data:  first of all, there were very few patients who were actually followed for 300 days, most of them were only followed for 6 weeks.  A graph like this implies that there are strong data points stretching out over the entire period.  Secondly, the linear plots do not show the degree of scatter in the data points.  There were no direct reports of the raw data in the study, only refined statistical distillations.  It would be much more informative to show all of the data points plotted out over time:  then one could see the times where most of the data were derived, the various courses of symptom change for each individual in the study, etc.  It would be a messier graph! -- but it would not mislead the viewer to immediately conclude that one medication is obviously better than the others.

In conclusion, the study really grabbed my attention when I first looked at it, but I found it to be much weaker than I thought, after reading it closely.

It does, however, provide a little bit of support for the idea that any one of these four antipsychotic medications are reasonable to try, in the treatment of psychotic symptoms.  I agree that quetiapine is a reasonable first choice, though the others could be reasonable also, depending on personal preference, past experience, side effect risks, etc.  I would still lean towards olanzapine for anticipated long-term treatment of severe symptoms.

Wednesday, June 9, 2010

A Learning Model of Psychological Change: the necessity of work & practice

It requires a great deal of work to bring about psychological change.

The brain is a dynamic organ, its development influenced by genetic predisposition combined with environmental experience.  Repeated environmental experience sculpts the brain, altering the strength of neuronal connections, neuronal activity, neurochemistry, and even neuronal growth or survival.

Various environmental adversities obviously predispose the brain to generate psychological symptoms, including specific incidents of trauma or neglect.

The manner in which adversity changes the brain is similar to the manner in which the brain changes in response to any other sort of experience:  sometimes there is sudden, intense change which can happen in an instant (e.g. a traumatic brain injury), but most often the brain changes gradually, after many repetitions of similar stimuli or similar inner processes.

Some environmental adversities are repetitive over months or years.  But often times the repetition which does further harm is generated by the brain itself:  in response to a problem, the brain's repetitious analysis and revisiting of the problem ends up causing consolidated change and ongoing symptoms. A great deal of the harm caused by specific instants of trauma is caused by the brain's reaction months or years after the trauma is over.  This reaction is akin to an autoimmune disease, in which the body's attempts to fight off disease end up causing inflammation, pain, and tissue damage. 

A symptom, such as anxiety or depressed mood, once generated from any cause, may lead to a cascade of brain changes which perpetuate and intensify the symptom.  The behavioural withdrawal which results from anxiety or depression changes the potential experiences the brain may incorporate in order to heal itself.  Even without overt behavioural withdrawal, an anxious or depressive state may cause the brain to perceive normal or pleasurable stimuli as dangerous, negative, boring, or unpleasant.   Each time this experience occurs, the brain changes further into a state of more deeply consolidated anxious or depressive disorder.  The theory of cognitive-behavioural therapy insightfully recognizes the role of thoughts as part of a cascade of phenomena perpetuating psychological illness.  Recurrent hostile, reflexively critical, cynical, pessimistic or negative thinking may at times have intellectual or philosophical validity; however, such thoughts, if highly recurrent, teach and sculpt the brain to make such a style of thinking an entrenched habit.  Such habits of thought are obvious causes for depression and diminished quality of life.    

My point here is to describe the brain as a "teachable" organ.  It is changed and sculpted by experience.  The source of this experience may be from the external environment or from the self-generated inner environment of the brain.   The degree to which the brain is sculpted by experience depends on the intensity of the experiences, multiplied by the time or frequency the experiences repeat themselves.

 In this regard, as I've stated before, the brain and its experiences are analogous to a growing garden, or a forest:  changes require time, care, knowledge about requirements, and energy.

Therapeutically, it is very clear to me that much work must be done in order to effect significant, lasting brain change. Likewise, a growing garden requires frequent care, particularly if there are adverse conditions caused from within (e.g. depleted soil, weeds) or from without (e.g. harsh weather, vandalism).  

The neurochemical environment can be an obstacle to brain change, in the same sense that abnormal soil chemistry may thwart the most earnest efforts of a gardener.  The "abnormal soil chemistry" may itself have been caused by an imbalanced garden ecology over many years, perhaps by genetic predispositions of the plants, and may conceivably be remediated and prevented in the long term by healthy gardening practices, yet an immediate external aid could be an immensely helpful catalyst to help these changes occur more easily and quickly.   Likewise, psychiatric medications can often be helpful catalysts for change.

But the key ingredient for brain change is experiential.  The type of experience capable of changing the brain substantially must be strong enough (i.e. it must employ a significant degree of the brain's capacity for attention, thought, feeling, and sensation, rather than simply being a passive or background activity), and must be frequent enough (i.e. it must occur regularly over a long period of time).

These requirements for experiential change are, as I've claimed before, similar to the requirements needed for learning a new language, or a musical instrument.

Without daily practice, therapy experiences which involve only one, or a few, appointments per week, are unlikely to cause significant psychological change, for the same reason that a language or music class once or twice a week will not lead to much language or music learning without doing daily homework.   The classes may be helpful or inspiring guides, but most of the change or learning will occur due to many hours of hard work, practicing, in-between classes.

Studies of different therapeutic strategies for treating psychological symptoms usually neglect to assess the most obvious and powerful source for change:  the amount and quality of the practice done.  It seems to me that most any style of therapy could work quite well (some slightly better than others, depending on the situation), provided that a great deal of disciplined work and practice takes place to learn new skills, and to effect change in the brain.

The analogy of musical practice leaps to mind again, in which quantity and repetition are important for learning, but also "quality."  To practice something passively, carelessly, or inattentively is often ineffectual, or sometimes even counterproductive, since one may be inculcating an unwanted habit.  Also, some types of practice may be excessively mechanical, or may be veering off a desired course too easily.

I am reminded of the "Suzuki" method of music education, which I think is wonderful, for the following reasons:
1) it encourages one to start young (i.e. at any age or level of ability)
2) it strongly encourages "playing by ear", listening frequently to recordings with strong attention to perceiving sound and tonal quality; this leads to a stronger and more rapidly developed appreciation for esthetics, as well as less dependency on external cues such as printed music.   The therapeutic analogy could be of  inviting frequent indirect involvement from a therapist or therapeutic system, rather than doing all "homework" completely on ones' own.
3) it strongly encourages group practice & performance, right from the beginning. This teaches not only solo musicianship, but also following and playing well with others, enjoying others, cooperation, being in a leadership role, having confidence with performance, and sharing one's gifts with others.   Also, practice is encouraged to be not just a solitary activity, but something which can be done with family or loved ones.  Therapeutically, I think it is strongly desirable to incorporate psychological work into group, family, and community settings.  
4) it emphasizes the importance of good posture.  Therapeutically, I think a fairly strict and disciplined framework to practice psychological techniques is healthy and reduces the likelihood of acquiring unhelpful habits.  On a literal level, I think a balanced exercise routine is psychologically healthy, including cardiovascular or strength training, sports, or a "postural" exercise such as yoga. 
5) it emphasizes the need for a lot of repetition.  Therapeutically, it may be necessary to practice techniques thousands of times, over a period of months or years, in order for them to become fluent.   Repetition should never be undertaken in a dull, mechanical way -- it needs to be infused with careful, reverent attention -- but it is absolutely needed in order to master anything. 

I challenge all those wishing to change longstanding psychological problems to frequently renew commitments to work hard, and to translate these commitments into a disciplined schedule of daily practice.  It may be that there are symptoms of  tiredness, amotivation, apathy, or a very negative or painful reaction to a broad variety of daily life experiences; these symptoms can prevent engagement with commitments, and can hinder the capacity to engage in disciplined work habits.  Also, the life stressors (work, money, relationship problems, etc) can take up so much time and energy that there is not much left to do regular psychological work.  Perhaps part of the therapeutic process at this stage is to problem-solve around ways to reduce stresses, reduce some of the symptoms, bolster energy, etc. as prerequisites to establishing a work plan.  Another view of this issue is that the "work" alluded to here could take place within any type of life stressor, it does not necessarily require a lot of extra time separate from other activities of daily living.