Friday, September 30, 2011

Pregabalin for generalized anxiety

There have been a variety of studies in the literature showing that pregabalin is effective for treating generalized anxiety.

The latest of such studies I have seen is published by Mark Boschen in the September 2011 issue of The Canadian Journal of Psychiatry (p.558-565).  

This article is a meta-analysis, and shows generally that pregabalin is effective compared to placebo, and has similar, if not greater, effectiveness than other medication options for treating generalized anxiety, such as SSRIs, venlafaxine, and benzodiazepines.

The most common doses have been in the 600 mg/day range, which I consider quite high, particularly since a reasonable dose range for pregabalin could be around 75-300 mg/day.  

The "limitations" admitted by the author include issues about dosing, and the fact that Pfizer has funded every published randomized study quoted in the article.

I believe that pregabalin could be a very useful option to try, if a medication trial is being considered for generalized anxiety treatment (of course, the first lines of therapy for generalized anxiety are CBT, relaxation-oriented therapies, meditation, exercise, etc.--but for many people these approaches are not sufficiently helpful).  Pregabalin has the advantage of having a quite different--and generally mild--side effect profile compared to other medications, and a what appears to be a fairly low (but I do not think zero) risk of addictiveness/dependence problems, particularly compared to benzodiazepines.

However -- the most obvious limitation of the literature findings is only mentioned briefly in passing by the author in the discussion:  it is hard to make a good conclusion about a treatment for anxiety when the duration of follow-up is only 4-8 weeks!  I believe that a study for this problem needs to extend for a year or more.  First of all, many treatments for anxiety can be acutely helpful, but then wear off substantially over time.  Arguably, having a beer every 4 hours could reduce GAD scores over a 4-week trial--but obviously this is not an acceptable long-term treatment!  (not only would there be multiple physical harms caused by this over a period of many months or years, but there would be substantial tolerance to anxiety reduction effects, which might only become apparent over many months; furthermore,there would be new psychiatric symptoms induced over a period of months and beyond).

It is not clear from the literature whether the acute benefits over 4-8 weeks from pregabalin would persist over a year or more, whether there would be tolerance, whether there would be longer-term emergent physical or psychiatric side-effects, dependence phenomena, trouble with withdrawal or discontinuation, etc.

Research of this type could be used --spuriously--to justify giving GAD patients benzodiazepines on a routine basis as well, despite the frequent and obvious problem of tolerance, dependence, cognitive problems, etc.  Most benzodiazepine studies are of similarly short duration, hence have very limited value to guide us for the long-term treatment decisions which are most important.

Yet, I do think that pregabalin is promising, and could be worth a cautious try, particularly if other approaches are not working well.

Thursday, September 29, 2011

Multi-dimensional nature of borderline personality symptom structure

Chmielewski et al. have published an article in the September 2011 edition of the Canadian Journal of Psychiatry in which they show that borderline personality is better described as having several separate symptom dimensions.

The benefit of having several dimensions instead of one could be illustrated by way of analogy:  suppose we are talking about heart disease.   One could simply describe all patients suffering a "heart attack" according to a single severity scale, perhaps including information of the amount of pain, degree of disability afterwards, etc.  This scale could be quite useful, but it would obscure a great deal of information about the group, and reduce the efficiency of treatment.   A multi-dimensional scale would instead look at several domains separately, such as perfusion abnormalities, rhythm abnormalities, and structural abnormalities.  Abnormal perfusion might be treated specifically with bypass surgery, rhythm problems with a pacemaker, and structural problems with a valve replacement etc.   Thus the management could become more meaningfully specific.

The authors of this paper about borderline personality show that a 3-factor model fit well to describe symptoms in borderline patients; a 1-dimensional model fit much more poorly.  The 3 factors are "affective dysregulation," "behavioural dysregulation," and "disturbed relations."    Affective dysregulation would refer to high intensity and lability of negative emotion, inappropriate anger, etc.   Behavioural dysregulation would refer to self-injurious behaviour, excessive or out-of-control behaviours such as binge eating, or I might add any sort of chemical or behavioural addiction.  Disturbed relations of course refers to interpersonal relationship problems.   One could see that these three domains would each influence the others, but part of a theoretical model is to consider to what degree problems in each domain could be considered primary.  (similarly, a blocked coronary artery would be a primary perfusion problem, but could in turn cause a secondary rhythm and structural problem in the heart). 

A particularly relevant remark from the authors comes in the discussion:  "...the current pattern of associations suggests that the glue that holds the BPD construct together may largely represent the general dysfunction or misery common across all forms of psychopathology and not just BPD."  So, the authors are hinting that we could perhaps do away with the BPD construct altogether, without any loss of insight,  and instead simply describe in succinct terms what the core symptoms are.  This makes sense to me.   I do believe that some of these core symptoms are extremely important to examine and address directly.  "Affective dysregulation" would be almost automatically addressed in any therapy environment, and "relationship dysfunction" is perhaps the most frequent topic of discussion (and perhaps transferential work) done in therapy.  But the "behavioural dysregulation"domain  I think is not quite so well-addressed in much therapeutic work.  I see this domain as the most common severe problem relatively more unique to those who fit into a "borderline personality" spectrum.  It is my own view to consider this domain through a type of addiction-medicine lens, as a set of problems which are highly destructive and addictive behavioural habits, often engaged in to cope with other symptoms, but which become independent problems with time.  This is similar to any other addiction;  alcoholism, for example,  may begin as alcohol consumption intended to calm nerves, deal with boredom, or to facilitate socialization, but in time becomes more and more a separate, self-contained behavioural and physiological addiction.

In my browsing through the literature as I was writing this post just now, I encountered a psychology master's thesis published online (by Edward Selby, M.Sc. 2007).  Here's a link:
Selby makes the case well that negative emotional cascades leading to behavioural dyregulation are strongly fuelled by rumination.  The events of behavioural dysregulation, such as self-injury, serve to distract one from the intense discomfort of rumination.  Here is a quote from the conclusion:
"the findings of this study provide preliminary evidence for an
emotional cascade model of dysregulated behavior. In this model high levels of rumination may cause extremely intense states of negative affect, which result in dysregulated behaviors that distract from rumination and reduce that state of negative affect. This study specifically linked rumination to drinking to cope, binge-eating behaviors, reassurance seeking, and urgency, and it is likely that rumination is linked to a variety of other deregulated behaviors. "

Rumination, of course, is another phenomenon common to much "general dysfunction or misery."  I am reminded how important it can be, as a practical therapeutic project with patients, to work on ways to move away from, or to let go of, rumination.  (see my previous post on rumination: