Last week’s post, Antipsychotics Over the Long Term: Thomas Insel Weighs In, elicited 20 comments. First, a quick summary of the post:
In his NIMH Director’s Blog, Dr Insel cited research in support of the proposition that, contrary to conventional psychiatric wisdom, antipsychotic medications may not always be a wise long-term option. According to Dr Insel:
It appears that what we currently call “schizophrenia” may comprise disorders with quite different trajectories. For some people, remaining on medication long-term might impede a full return to wellness. For others, discontinuing medication can be disastrous.
Various schizophrenia treatment guidelines such as the one issued by the American Psychiatric Association advocate antipsychotic treatment over the long term, if not for life. The catch is that the supporting evidence is weak, or even non-existent. What psychiatry calls a long-term drug trial typically lasts six-to-12 months. There are no trials beyond two years. In other words, there are no long-term trials. None.
Moving on ...
The supporting evidence for the long-term treatment of bipolar disorder is equally underwhelming. We are told that relapse is common in bipolar, that we need to stay on our meds. But for how long? Especially if the med in question happens to be an antipsychotic.
In the short term, to pull us out of a crisis, one finds little opposition to the use of antipsychotics. These are the miracle drugs that stop both psychosis and mania dead in their tracks, and there are no shortage of trials to prove it. Some of these agents even work as antidepressants.
But pulling us out of crisis is a very different proposition than getting well and staying well, and here the studies don’t help us at all. According to the British Association for Psychopharmacology’s (BAP) Evidence-Based Guidelines For Treating Bipolar Disorder (2009), so-called “long-term” trials employ a “relapse prevention design.” The patients who enter these studies have first been successfully treated in a crisis situation, then are either kept on the same drug or given a placebo.
At this stage, the study has already been severely compromised. In the words of the BAP: “This enriches the sample for both efficacy and tolerability.” In other words, those who have not already done well on the test med have been weeded out of the study. Nevertheless, the BAP says these studies are useful if the clinician is looking to keep a patient on same med.
Thus, the med that got you well (or at least out of crisis) may keep you well (that is, prevent a relapse). BAP cites a 48-week study in support of this proposition (Tohen et al, 2006). At the same time, the BAP notes: “The excess of early relapse in this study suggests a contribution from withdrawal effects to the apparent effect size.”
This is a very difficult sentence to translate. The BAP seems to be suggesting that some of the relapses in the placebo group could be attributable to the withdrawal effects of the med (in this case Zyprexa) rather than to the natural course of the illness. This is a problem that plagues long-term studies, and is well-known to clinicians and researchers.