Leo Sher, M.D.

A seminal research work, “Amisulpride and olanzapine followed by open-label treatment with clozapine in first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three-phase switching study” has recently been published in Lancet Psychiatry (1). A large international research group led by Professor René S. Kahn examined whether switching antipsychotic medications or early use of clozapine improves outcome in first-episode schizophrenia.

The study was performed in 27 psychiatric hospitals and clinics in Austria, Belgium, Bulgaria, Czech Republic, Denmark, France, Germany, Israel, Italy, the Netherlands, Poland, Romania, Spain, Switzerland, and the UK. The study consisted of 3 phases: the first phase was an open-label, single treatment arm; the second phase was a randomized, double-blind design; and the third phase was an open label, single-treatment arm.

Patients aged 18–40 years who met criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder were treated for 4 weeks with amisulpride orally in an open-label design (phase 1). Patients who did not meet criteria for symptomatic remission at 4 weeks were randomly assigned to continue amisulpride or switch to olanzapine during a 6-week double-blind phase, with patients and staff masked to treatment allocation (phase 2). Patients who were not in remission at 10 weeks were given clozapine for an additional 12 weeks in an open-label design (phase 3).

Fifty-six percent patients achieved remission after phase 1. Patients who were not in remission continued to the 6-week double-blind switching trial. Forty-five percent patients on amisulpride versus 44% on olanzapine achieved remission (p=0.87). Of the patients who were not in remission after 10 weeks of treatment, 70% started on clozapine; 64% patients completed the 12-week clozapine treatment, and 28% achieved remission.

Current guidelines recommend that clozapine should be offered to patients who have not responded to treatment with two different antipsychotic drugs. The results of this study indicate that for most patients in the early stages of schizophrenia, symptomatic remission can be achieved using a simple treatment algorithm comprising the sequential administration of amisulpride and clozapine. Since switching to olanzapine did not improve outcome, clozapine should be used after patients fail a single antipsychotic trial.

Reference

1. Kahn RS, Winter van Rossum I, Leucht S, McGuire P, Lewis SW, Leboyer M, Arango C, Dazzan P, Drake R, Heres S, Díaz-Caneja CM, Rujescu D, Weiser M, Galderisi S, Glenthøj B, Eijkemans MJC, Fleischhacker WW, Kapur S, Sommer IE; OPTiMiSE study group. Amisulpride and olanzapine followed by open-label treatment with clozapine in first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three-phase switching study. Lancet Psychiatry. 2018 Oct;5(10):797-807.