Polypharmacy for Schizophrenia

This is what people out there have been doing for a long time. However, the evidence base of this type of practice is not substantial. A new paper published by Essock and colleagues in the July 2011 issue of the green journal tries to answer the question. Contrary to expectations, polypharmacy, while not as well tolerated as monotherapy, seems to be preferred. Due to lack of blinding, it is not clear though, if this is due to the patient's or provider's preferences (or biases) or both.

On my Faculty of 1000 review of the paper (which we can also find HERE on the Faculty of 1000 site - subscription required) this paper got a 6 and was considered a new finding. Here is the entire text of the comment:

"Is polypharmacy all that bad? Polypharmacy with more than one antipsychotic is generally not recommended but is often prescribed as a result of 'desperation' in response to the failure of monotherapy. Such failures may be due to a combination of poor or partial response and/or adverse effects resulting in partial compliance. This paper by Essock et al. may signal the beginning of a paradigm change where future polypharmacy randomized controlled trials (RCTs), already informing practice in other medical disciplines (e.g. oncology, neurology and infectious diseases/AIDS), can address some of the complex questions that psychiatrists face on a daily basis. In addition, Essock et al.'s study shows that engrained expectations -- the official dogma -- can and should be challenged.

Directly challenging the traditional textbook-based psychopharmacological wisdom of 'less is more', Essock et al. compared continuing schizophrenia patients on two antipsychotics with switching to a single antipsychotic. Using a naturalistic randomized control trial design, Essock et al. found that, on average, time to discontinuation or change in medication was shorter in the monotherapy group, suggesting that, at least for some patients, polypharmacy might be better than monotherapy, although this was not reflected by an increase in general symptoms or more hospitalizations in those that switched. Importantly, most patients (69%) were successfully switched to monotherapy. Switchers lost weight (decreased body mass index [BMI] by 0.5 points), while the polypharmacy group gained 0.3 points. So, switching to monotherapy works for the majority of patients and on average results in weight loss. At 6 months, 86% of patients continued on polypharmacy versus 69% who stayed on monotherapy, suggesting that, regardless of practice guidelines, at least for some patients two antipsychotics can work better than one.

While these findings are thought-provoking, future studies looking at mono- versus polypharmacy comparisons should carefully address the issue of potential bias due to unblinded switching, which is a potential confounder in Essock et al.'s study. Further research is clearly indicated to tease out what were the hidden benefits of combination therapy."

© Copyright Adrian Preda, M.D.