Augmenting clozapine with sertindole: a double-blind, randomized, placebo-controlled study

Area of Science:

• Psychiatry
• Pharmacology

Background:

• Clozapine is effective for treatment-resistant schizophrenia, but many patients require augmentation.
• Antipsychotic augmentation strategies are common, yet evidence is limited.
• Sertindole, a nonsedating atypical antipsychotic, was investigated for clozapine augmentation due to its receptor affinity profile.

Purpose of the Study:

• To evaluate the efficacy and safety of sertindole augmentation in patients with schizophrenia inadequately responding to clozapine.

Main Methods:

• A 12-week, double-blind, randomized, placebo-controlled trial.
• Included patients with International Classification of Diseases, 10th Revision schizophrenia (F20.0-F20.3) on stable clozapine therapy.
• Assessed outcomes using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), and other measures.

Main Results:

• Sertindole augmentation was not superior to placebo on PANSS total or subscale scores, CGI, or quality of life measures.
• No significant increase in adverse effects was observed compared to placebo.
• Four patients on sertindole experienced psychosis worsening, with two requiring hospitalization.
• A statistically significant QTc prolongation (12 ms) was noted in the sertindole group versus placebo.

Conclusions:

• Clozapine augmentation with sertindole offers no demonstrated benefit over placebo for patients with schizophrenia.
• The strategy may carry risks, including potential worsening of psychosis and QTc prolongation.
• Clinicians should carefully consider the lack of efficacy and potential risks before using sertindole augmentation.