COPENHAGEN – Recent studies emphasize the long-term merits of extending antipsychotic therapy beyond 1 year for patients in remission after a first psychotic episode, Mark Weiser, MD, observed at the annual congress of the European College of Neuropsychopharmacology.
Bruce Jancin/MDedge News
Dr. Mark Weiser
Another emerging theme in the research literature, albeit a somewhat heretical one, is the value of antipsychotic polypharmacy, added Dr. Weiser, professor and chairman of the department of psychiatry at Sackler Faculty of Medicine, Tel Aviv University.
“Polypharmacy might not be so bad,” he declared in a keynote lecture in which he highlighted recent major publications addressing issues involving pharmacotherapy of schizophrenia.
“When we were residents, we were all taught that it’s not good to give two antipsychotics together, that all antipsychotics work only through dopamine D2 [receptor] blockade, hence there’s no point in giving more than one antipsychotic because all you’re doing is increasing side effects. But maybe it’s not as simple as that,” the psychiatrist said.
Exhibit 1: A recent Finnish national registry study of 62,250 patients with schizophrenia featuring up to 20-year follow-up showing that any antipsychotic polypharmacy was associated with a significantly lower risk of rehospitalization, compared with any antipsychotic monotherapy. The combination that stood out as having the lowest rehospitalization risk was clozapine plus aripiprazole, with a 14%-23% lower risk than for clozapine alone, which was the most effective monotherapy (JAMA Psychiatry. 2019 May; 76[5]:499-507).
Dr. Weiser pronounced himself a firm believer in the Finnish experience.
“The reason I think that this is true is that it’s exactly what I find in my own VA data,” he said.
Indeed, he and his coinvestigators are preparing to publish the results of their longitudinal study of 37,368 schizophrenia patients in the U.S. Veterans Affairs system. A key finding was that patients on antipsychotic polypharmacy had a longer time to treatment discontinuation than did those on monotherapy.
“Polypharmacy, at least in real-world study designs, seems to be good,” he noted.
Moreover, even in the world of highly selective randomized clinical trials, polypharmacy appears to fare pretty well as a treatment strategy, Dr. Weiser noted. A recent meta-analysis of six RCTs totaling 341 patients showed that switching patients from two antipsychotics to one was associated with a 2.2-fold increased risk of study discontinuation, although the investigators rated the quality of the trials as low to very low (Schizophr Res. 2019 Jul;209:50-7).
“I’m doing more polypharmacy now because of these data,” Dr. Weiser said. “My understanding of the polypharmacy data is that it’s not just blocking dopamine that’s important for treatment efficacy in schizophrenia.”
Getting a handle on first-episode psychosis
Dr. Weiser was a coinvestigator in the European Commission–funded OPTiMiSE study, in which 446 patients with first-episode schizophrenia or schizophreniform disorder in 14 European countries and Israel received 4 weeks of oral amisulpride. Then, if they were not in symptomatic remission, they were randomized double-blind to 6 weeks more of amisulpride or a switch to olanzapine. Those who weren’t in remission at 10 weeks were then placed on 12 weeks of open-label clozapine.