Evaluation of the pharmacodynamic interaction effect of augmentation agents with clozapine in patients with treatment-resistant schizophrenia: A simulation study of clinical data.

Autor: Mishra A; Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar 751019, India., Maiti R; Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar 751019, India., Ramasubbu MK; Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar 751019, India., Srinivasan A; Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar 751019, India. Electronic address: anandsrinivasan@aiimsbhubaneswar.edu.in.
Jazyk: angličtina
Zdroj: Psychiatry research [Psychiatry Res] 2024 Aug; Vol. 338, pp. 115989. Date of Electronic Publication: 2024 Jun 01.
DOI: 10.1016/j.psychres.2024.115989
Abstrakt: Introduction: The aim of the study was to evaluate interaction effect of various augmentation strategies with clozapine in patients with Treatment-resistant schizophrenia.
Methods: Data was extracted for change in positive and negative syndrome scale (PANSS) or brief psychiatric rating scale (BPRS) scores for monotherapy with various antipsychotic agents alone and their combination with clozapine. Individual patient data was generated using simulation of data (factorial trial framework) from published clinical trials for sample sizes from eight to 400 to evaluate interaction effect through linear modeling. Dose equivalents were calculated, and best fit models were determined for simulated data.
Results: The polynomial model was found to be the best fit for the simulated data to determine interaction effect of combination. The clozapine augmentation with risperidone and ziprasidone was found to be antagonistic, whereas it was additive for haloperidol, aripiprazole, and quetiapine. A synergistic effect was observed for ECT combined with clozapine (Interaction effect: -7.62; p <0.001). A sample size of 250-300 may be sufficient to demonstrate a clinically significant interaction in future trials.
Conclusion: Clozapine may be augmented with electroconvulsive therapy, leading to the enhancement of antipsychotic effect. Though some antipsychotics like aripiprazole demonstrate additive effects, they may also add to the adverse effects.
Competing Interests: Declaration of competing interest None.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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