Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review

Area of Science:

• Psychiatry
• Cardiology
• Pharmacology

Background:

• Clozapine is a vital antipsychotic for treatment-resistant schizophrenia, offering benefits with minimal extrapyramidal symptoms.
• However, clozapine is associated with significant cardiometabolic side effects, potentially linked to autonomic dysfunction.
• Understanding the mechanisms of autonomic dysfunction is crucial for managing clozapine's adverse cardiovascular events.

Purpose of the Study:

• To systematically review the existing literature on autonomic dysfunction in patients treated with clozapine.
• To summarize associated cardiovascular side effects and explore potential management strategies.
• To identify gaps in research and highlight the need for improved interventions.

Main Methods:

• A comprehensive literature search was conducted across EMBASE, MEDLINE, and EBM Cochrane databases.
• Keywords included terms related to antipsychotics, schizophrenia, cardiovascular diseases, clozapine, and autonomic function.
• 37 studies were reviewed, with a focus on those reporting autonomic dysfunction and cardiovascular side effects.

Main Results:

• Clozapine treatment was associated with adverse cardiovascular events including myocarditis, orthostatic hypotension, and tachycardia.
• These effects are attributed to sympathetic hyperactivity, reduced vagal tone, receptor blockade, decreased heart rate variability, and elevated catecholamines.
• Only 16 of the reviewed studies utilized interventions, with limited success reported in case reports for managing tachycardia and blood pressure fluctuations.

Conclusions:

• There is a significant lack of clinical studies investigating clozapine-induced autonomic dysfunction.
• Interventions for managing associated cardiovascular side effects are limited and often based on case reports.
• Further research with robust study designs and autonomic testing is essential for preventing and treating clozapine-related cardiovascular complications.