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Beyond clozapine – what options do we have in clozapine resistant schizophrenia?

Published online by Cambridge University Press:  26 August 2025

A. C. Matias ,
T. Vieira ,
A. Ferreira Silva ,
R. Machado Lopes ,
C. Almeida Rodrigues ,
F. Marinho Santos  and
P. Fonseca Coelho
A. C. Matias*
Affiliation:
Psychiatry and Mental Health Department, Unidade Local de Saúde do Médio Tejo, Tomar, Portugal
T. Vieira
Affiliation:
Psychiatry and Mental Health Department, Unidade Local de Saúde do Médio Tejo, Tomar, Portugal
A. Ferreira Silva
Affiliation:
Psychiatry and Mental Health Department, Unidade Local de Saúde do Médio Tejo, Tomar, Portugal
R. Machado Lopes
Affiliation:
Psychiatry and Mental Health Department, Unidade Local de Saúde do Médio Tejo, Tomar, Portugal
C. Almeida Rodrigues
Affiliation:
Psychiatry and Mental Health Department, Unidade Local de Saúde do Médio Tejo, Tomar, Portugal
F. Marinho Santos
Affiliation:
Psychiatry and Mental Health Department, Unidade Local de Saúde do Médio Tejo, Tomar, Portugal
P. Fonseca Coelho
Affiliation:
Psychiatry and Mental Health Department, Unidade Local de Saúde do Médio Tejo, Tomar, Portugal
*
*Corresponding author.

Abstract

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Introduction

Schizophrenia is one of the most disabling mental disorders, affecting around 1% of the population. Although most patients respond to antipsychotic treatment, one third have a limited response to antipsychotic medication, being considered treatment resistant schizophrenia (TRS). Clozapine is the only effective medication for TRS, but 30-40% of TRS patients do not respond to it. Patients with schizophrenia who do not respond to clozapine experience more severe disability, persistent symptoms, a lower quality of life and incur higher economic costs compared to those who respond to treatment.

Objectives

The aim of the present study is to review evidence for therapeutic strategies for patients with treatment-resistant schizophrenia not responding to clozapine.

Methods

Review of the literature regarding treatment-resistant schizophrenia not responding to clozapine. The research was carried out through the PubMed® database, using the terms “treatment resistant schizophrenia”, “schizophrenia resistant to clozapine” and “clozapine augmentation”.

Results

For patients with treatment-resistant schizophrenia who do not respond to clozapine, several therapeutic strategies have been explored. These include pharmacological approaches, non-pharmacological interventions and brain stimulation procedures [Electroconvulsive Therapy (ECT) and Transcranial Magnetic Stimulation (TMS)]. However, the evidence is weak and the reported benefits were modest.

Conclusions

The current evidence is weak for efficacy of pharmacological augmentation strategies to clozapine. There are contradictory data regarding ECT and clozapine augmentation. More studies are necessary to clarify the potential of these strategies in order to manage these complex patients.

Disclosure of Interest

None Declared

Information

Type
Abstract
Information
European Psychiatry , Volume 68 , Special Issue S1: Abstracts of the 33rd European Congress of Psychiatry , April 2025 , pp. S1106
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of European Psychiatric Association
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