The recently published randomized, placebo-controlled trial (RCT) by my colleagues and me confirms what guidelines have been telling us for some time now—that the evidence does not support the use of antipsychotic polypharmacy. Yet the practice continues in about 1 in 4 patients. Are clinicians that indifferent to evidence-based medicine or do these figures reflect the fact that the issue is not so straightforward? I suggest the latter.
Such categorical positions rarely hold up in medicine; our own study reminds us of this. Indeed, a fellow clinical researcher at my center recently recalled aloud that one of his patients who participated in this trial experienced clinical worsening when the second antipsychotic was withdrawn. I could conjecture reasons for this; for example, in our study, discontinuation of the second antipsychotic was abrupt rather than gradual. It remains, though, that some individuals do seem to worsen when polypharmacy is changed to monotherapy, and unfortunately we have no way of accurately predicting who these individuals are (just as we have no clearly established rationale for why or how a change to monotherapy might benefit other patients). The net result is that we have many patients who are unnecessarily receiving combined antipsychotic therapy. This situation is not unlike the high-dose antipsychotic story. Almost every clinician working with patients who have schizophrenia can identify someone who has required high doses to maintain response, but this group of patients is far outweighed by those who fail to benefit from such a strategy./.../