Distinguishing psychopathology from medication-induced tachycardia in patients treated with clozapine: is it anxiety or a medication side effect?

Objectives The purpose of this paper is to review the characteristics and mechanisms of clozapine-induced tachycardia and anxiety-induced tachycardia. The paper aims to provide a comprehensive understanding of the prevalence, risk factors, underlying causes, and clinical features of each condition to assist the clinician in distinguishing between the various causes and mechanisms that may contribute to tachycardia. Methods A comprehensive literature search was conducted using the MEDLINE and Scopus databases with keywords including "clozapine", "tachycardia", "anxiety", "cardiac effects", and "adverse effects". The selection process included screening of titles and abstracts, followed by full-text review of relevant studies. Data on study design, sample size, patient demographics, incidence of tachycardia, and proposed mechanisms were extracted and synthesized to highlight key findings, identify knowledge gaps, and suggest areas for future research. Results Clozapine-induced tachycardia has been reported in approximately 25-50% of patients, particularly during the early stages of treatment. Proposed mechanisms include alpha-adrenergic receptor antagonism, interactions with muscarinic receptors, effects on plasma norepinephrine levels, and inflammatory pathways. Risk factors include advanced age, high dose, rapid dose titration, and comorbid conditions such as thyroid dysfunction and metabolic disorders. Anxiety-induced tachycardia results from activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased heart rate and cardiovascular stress. Conclusions Clozapine is effective in treating resistant schizophrenia but carries significant cardiovascular risks, including tachycardia. Differentiation between clozapine-induced and anxiety-induced tachycardia is critical for appropriate management. Regular cardiovascular monitoring, dose adjustment, and lifestyle modifications are essential to reduce these risks. Further research is needed to clarify the exact incidence of clozapine-induced tachycardia, explore specific mechanisms, and develop effective management strategies. Understanding the interaction between clozapine and tachycardia, as well as the impact of comorbid anxiety, is critical to optimizing patient care and ensuring safe long-term use of clozapine.