The ever-growing case for clozapine in the treatment of schizophrenia: an obligation for psychiatrists and psychiatry

Abstract

A still expanding body of evidence unequivocally supports the superior efficacy of clozapine compared to other antipsychotics for a considerable number of outcome measures in the treatment of schizophrenia including positive symptoms, negative symptoms, aggression and suicidality. Therefore, clozapine remains the gold standard not only for treatment-resistant schizophrenia but also for a larger number of patients with a poor course of illness. Furthermore, recent meta-analytical evidence clearly demonstrates the superiority of clozapine for reducing all-cause mortality. This finding indicates that clozapine is one of the most potent means to reduce the outrageous mortality gap faced by patients with schizophrenia. Despite its unmatched and wide-ranging efficacy as well as its cost effectiveness, clozapine remains alarmingly underutilized throughout the industrialized world even though patients’ acceptance of clozapine treatment is surprisingly high. While limited, existing evidence indicates that this is primarily due to psychiatrists’ concerns regarding safety and side effect management possibly resulting from insufficient clinical training in using clozapine. This would imply that many patients are never offered clozapine in the first place despite a clear indication. We argue that psychiatrists have an urgent obligation to address this issue and ensure sufficient availability of this vital treatment option. If our fields’ commitment to shared decision-making is to be genuine, we must not exclude patients from the potentially life-changing decision to initiate clozapine treatment. Therefore, concerted research and mental-health policy efforts should focus on identifying barriers for clozapine utilization and effective measures to overcome them. On the one hand, this will require structural changes to clinical training and care systems. On the other and hand – and at least as important – it will require a continued commitment of individual psychiatrists to align their attitudes and clinical practices more closely with the existing evidence and patient preference. The benefits for patients, their families, clinical psychiatry and society will be substantial.

Exploring clozapine use in severe psychiatric symptoms associated with autism spectrum disorder: A scoping review

“…Possible reasons may include the practical and ethical barriers to conducting experimental studies with clozapine in a vulnerable population. In addition, “clozapine phobia” (clinicians’ fear of initiating this treatment due to its serious health risks) (Pandarakalam, 2019) results in its underutilization in treatment-resistant psychotic disorders worldwide (Law et al, 2023), even considering the superior efficacy and reduced all-cause mortality (Bittner et al, 2023). It is worth questioning whether an analogous phenomenon impacts the development of studies on clozapine in the ASD psychopharmacology field.…”

“…Clozapine also effectively reduces suicidal behaviors, violent episodes, and substance abuse in patients with schizophrenia. Furthermore, its administration is associated with lower morbidity and mortality rates and improvement of quality of life and functionality in patients with psychotic disorders (Bittner et al, 2023; Khokhar et al, 2018; Qubad and Bittner, 2023).…”