Switching anti-psychotic medications does not improve clinical outcomes in patients with first-episode schizophrenia who haven’t responded to treatment, Mount Sinai researchers have shown for the first time.

The data suggest that if a patient fails to achieve remission on the first antipsychotic drug, switching to a different drug in the same class is no more effective then remaining on the same medication and waiting to see if remission is achieved at a later stage.

The results of the study were published online in The Lancet Psychiatry on Monday, August 13.

The OPTIMISE trial (Optimization of Treatment and Management of Schizophrenia in Europe) was conducted in 14 European countries and Israel, in 27 centers that included general hospitals and psychiatric specialty clinics. Four hundred and forty-six patients with schizophrenia or schizophreniform disorder were treated for 4 weeks with up to 800 mg a day of amisulpride, an antipsychotic.

Patients who did not achieve remission at 4 weeks were randomized to continue amisulpride or switch to up to 20 mg/day of olanzapine, a different antipsychotic, during a 6-week double-blind phase. Patients who were not in remission at 10 weeks were given up to 900 mg/day of clozapine, an antipsychotic mainly used for schizophrenia patients who do not improve following the use of other medications, for an additional 12 weeks.

Clozapine is typically not prescribed as early as 10 weeks into treatment, but the researchers said the data supported its earlier use in such cases.

The research team found that switching from amisulpride to olanzapine in first-episode schizophrenia did not improve clinical outcomes: Remission rates were not significantly different between these treatments.

“In clinical practice, when a patient has not responded to the initial treatment, they are often switched from one antipsychotic medication to another,” said the study’s first author and Principal Investigator, Rene S. Kahn, MD, PhD, Esther and Joseph Klingenstein Professor and System Chair of Psychiatry at the Icahn School of Medicine at Mount Sinai. “However, there is surprisingly little evidence that this improves clinical outcomes. Our study results show that trying another antipsychotic in schizophrenia patients who fail to achieve remission is no longer necessary. Instead more aggressive treatment, including treatment with clozapine, one of the most effective antipsychotics available, can be started earlier, which could potentially save time and reduce suffering.”

Other institutions involved in the study include UMC Utrecht, King’s College London, Technische Universität München, University of Manchester, and Ludwig-Maximilians—University of Munich.