Amisulpride and olanzapine combo as an alternative to monotherapy in schizophrenia? Study sheds light

Germany: The combination of amisulpride and olanzapine therapy could be used in schizophrenia patients as an alternative to monotherapy in certain clinical situations, but side effects should also be considered, states a recent study. The study appears in the journal The Lancet Psychiatry.

"The advantages of this specific combination have to weighed against a higher propensity for side effects," Christian Schmidt-Kraepelin, and researchers team wrote in their study.

Evidence-based guidelines generally do not recommend combining antipsychotics in schizophrenia treatment despite it being a common practice. Otherwise, evidence remains inconclusive particularly regarding specific combinations. Dr. Schmidt-Kraepelin and the team aimed to test whether a combination of amisulpride plus olanzapine is more effective than either intervention as a monotherapy.

For this purpose, the researchers conducted a 16-week, randomised, double-blind, controlled trial at 16 psychiatric in-patient centres throughout Germany. The trial included adults adults aged 18–65 years with non-first episode schizophrenia or schizoaffective disorder and with a Positive and Negative Syndrome Scale (PANSS) total score of at least 70 and at least two items of the positive symptoms subscale rated at least 4. They were randomly assigned to receive 16 weeks of treatment with either amisulpride plus olanzapine, amisulpride plus placebo, or olanzapine plus placebo (1:1:1).

Comparison was done between flexibly dosed monotherapy of oral amisulpride (amisulpride plus placebo, 200–800 mg per day) or olanzapine (olanzapine plus placebo, 5–20 mg per day) and a combination of amisulpride plus olanzapine. Symptom reduction measured by the PANSS total score after 8 weeks was the primary outcome.

13 692 patients were assessed for eligibility between June 15, 2012, and Dec 15, 2018. 13 364 patients were excluded, and 328 were then randomly assigned to an intervention group. 112 patients were randomly assigned to receive amisulpride plus olanzapine, 109 were randomly assigned to receive amisulpride plus placebo, and 107 were randomly assigned to receive olanzapine plus placebo.

The primary outcome was analyzed in 321 patients. Among the 321 patients who were randomly assigned to intervention groups and analysed for the primary outcome, 229 (71%) were male, 92 (29%) were female; the mean age was 40·2 years; and 296 (92%) were White and 25 (8%) were classified as other ethnicity.