New York—With no established treatment algorithm for schizophrenia patients, clinicians often are uncertain whether to switch antipsychotics or to initiate early use of clozapine to improve outcomes after the first episode.

That’s the dilemma tackled by Mount Sinai Medical School researchers and colleagues. Their results, touted as the first of their kind, were published in The Lancet Psychiatry.

Ultimately, the study authors determined that switching antipsychotic medications does not improve clinical outcomes in patients with first-episode schizophrenia who haven’t responded to treatment.

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. Participants were 446 patients with schizophrenia or schizophreniform disorder who were treated for 4 weeks with up to 800 mg per day of amisulpride.

Patients who did not achieve remission at 4 weeks were randomized to continue amisulpride or to switch to up to 20 mg per day of olanzapine during a 6-week double blind phase. After 10 weeks, participants who were not in remission were dosed with up to 900 mg per day of clozapine for an additional 12 weeks. Researchers said that data supported earlier use of clozapine, which usually is not prescribed as early as 10 weeks into treatment.

Results indicate that, of the 446 patients in the intent-to-treat sample, 83% completed open-label amisulpride treatment, and 56% achieved remission after phase 1. Of those who continued to the 6-week double-blind switching trial, 45% patients on amisulpride versus 44% on olanzapine achieved remission.

Of the 40 patients who were not in remission after 10 weeks of treatment, 70% were prescribed clozapine, 64% completed the 12-week treatment, and 28% achieved remission.

The study team interpreted the data to mean 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 than remaining on the same medication and waiting to see if remission is achieved over time.

“In clinical practice, when a patient has not responded to the initial treatment, they are often switched from one antipsychotic medication to another,” explained the study’s first author and principal investigator Rene S. Kahn, MD, PhD. “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.”
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