Current perspectives on the recognition and management of treatment-resistant schizophrenia: challenges and opportunities.

Abstract

Introduction: Treatment-resistant schizophrenia (TRS) significantly impacts patients with schizophrenia, leading to a high disease burden, reduced quality of life, and functional impairment. Many patients fail to respond to standard antipsychotic treatments, requiring specialized therapeutic approaches. Clozapine remains the only approved treatment for patients with TRS, demonstrating effectiveness in reducing symptoms, hospitalizations, and risk of suicide. However, its use is often delayed due to concerns about adverse events, and the need for ongoing monitoring.

Areas covered: This critical perspective incorporates insights from psychiatrists in Greece and a comprehensive literature analysis that includes clinical guidelines and systematic reviews. It highlights strategies for early diagnosis and timely initiation of clozapine, while emphasizing practical challenges in its use. Recommendations emphasize reducing treatment delays and overcoming barriers such as inadequate training and hesitancy among clinicians. A comprehensive literature search was conducted on PubMed, Google Scholar, and Cochrane Library without any date restrictions to ensure a thorough review of available evidence. The initial literature search was carried out in September 2024, with a subsequent search conducted in March 2025.

Expert opinion: International guidelines consistently recommend clozapine as the first-line treatment for patients with TRS; nevertheless, the authors advocate enhanced awareness to optimize use. Most adverse events can be effectively managed with proper oversight, and early initiation is crucial to improving remission rates and the quality of life of patients with TRS. There is a need for systemic improvements in clinical practice, which requires evidence-based guidance to better address treatment efficacy in this challenging patient population.