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Randomized Controlled Trial
. 2022 Nov 18;48(6):1273-1283.
doi: 10.1093/schbul/sbac068.

Changing the Antipsychotic in Early Nonimprovers to Amisulpride or Olanzapine: Randomized, Double-Blind Trial in Patients With Schizophrenia

Stephan Heres  1   2 , Joachim Cordes  3   4 , Sandra Feyerabend  3   4 , Christian Schmidt-Kraepelin  3   4 , Richard Musil  5 , Michael Riedel  5   6 , Ilja Spellmann  5   7 , Berthold Langguth  8 , Michael Landgrebe  8   9 , Elmar Fran  8 , Camelia Petcu C  10 , Eric Hahn  11 , Tam M T Ta  11 , Valentin Matei  10 , Liana Dehelean  12   13   14   15 , Ion Papava  12   13 , F Markus Leweke  16   17 , Till van der List  17   18 , Simona C Tamasan  19 , Fabian U Lang  20 , Dieter Naber  21 , Stephan Ruhrmann  22 , Claus Wolff-Menzler  23 , Georg Juckel  24 , Maria Ladea  25 , Cristinel Stefanescu  26 , Marion Lautenschlager  27   28 , Michael Bauer  29 , Daisy Zamora  2   30 , Mark Horowitz  31 , John M Davis  31 , Stefan Leucht  2
Affiliations
Randomized Controlled Trial

Changing the Antipsychotic in Early Nonimprovers to Amisulpride or Olanzapine: Randomized, Double-Blind Trial in Patients With Schizophrenia

Stephan Heres et al. Schizophr Bull. .

Abstract

Background and hypothesis: Meta-analyses have shown that the majority of patients with schizophrenia who have not improved after 2 weeks of treatment with an antipsychotic drug are unlikely to fully respond later. We hypothesized that switching to another antipsychotic with a different receptor binding profile is an effective strategy in such a situation.

Study design: In total, 327 inpatients with an acute exacerbation of schizophrenia were randomized to double-blind treatment with either olanzapine (5-20 mg/day) or amisulpride (200-800 mg/day). Those patients who had not reached at least 25% Positive-and-Negative-Syndrome-Scale (PANSS) total score reduction from baseline after 2 weeks (the "non-improvers") were rerandomized double-blind to either staying on the same compound ("stayers") or to switching to the other antipsychotic ("switchers") for another 6 weeks. The primary outcome was the difference in the number of patients in symptomatic remission between the combined "switchers" and the "stayers" after 8 weeks of treatment, analyzed by logistic regression.

Study results: A total of 142 nonimprovers were rerandomized at week two. 25 (45.5 %) of the 'stayers' compared to 41 (68.3 %) of the "switchers" reached remission at endpoint (p = .006). Differences in secondary efficacy outcomes were not significant, except for the PANSS negative subscore and the Clinical-Global-Impression-Scale. "Switchers" and "stayers" did not differ in safety outcomes.

Conclusions: Switching "non-improvers" from amisulpride to olanzapine or vice-versa increased remission rates and was safe. The superiority in the primary outcome was, however, not paralleled by significant differences in most secondary efficacy outcomes and the effect was only apparent at the last visit making replications of longer duration necessary.

Keywords: pharmacological treatment/change; pharmacotherapy.

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Figures

Fig. 1.
Fig. 1.
Study design.
Fig. 2.
Fig. 2.
Percentages of subjects in remission at different time points and study endpoint.
Fig. 3.
Fig. 3.
CONSORT diagram.
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