quetiapine-fumarate and Myocardial-Infarction

Chlorprothixene is commonly used off-label in low doses for sedative-hypnotic purposes although it might carry a risk of cardiometabolic adverse events due to its pharmacodynamic profile. We investigated the risk of diabetes and major adverse cardiovascular events (MACE) with use of low-dose chlorprothixene, compared with use of low-dose quetiapine in a nationwide cohort study, including all new users of low-dose chlorprothixene (n = 81 328) and low-dose quetiapine (n = 91 163) in Denmark 2000-2017. Main outcomes were diabetes and MACE (myocardial infarction, stroke and death from cardiovascular causes). The association between cumulative dose of chlorprothixene and the outcomes was tested in a case-control analysis. Low-dose chlorprothixene use was associated with increased risk of diabetes (intention-to-treat [ITT]-hazard ratio [HR]: 1.16; 95% CI: 1.08-1.25), compared with low-dose quetiapine use. This association strengthened when follow-up was restricted to time on treatment (as-treated [AT]-HR: 1.34; 95% CI: 1.14-1.56). Low-dose chlorprothixene use was also associated with increased risk of MACE (ITT-HR: 1.12; 95% CI: 1.04-1.21) and stroke (ITT-HR: 1.21; 95% CI: 1.06-1.37) but not with myocardial infarction (ITT-HR: 1.11; 95% CI: 0.95-1.30) nor death from cardiovascular causes (ITT-HR: 1.07; 95% CI: 0.96-1.20). Cumulative dose of chlorprothixene ≥6000 mg was associated with increased risk of diabetes (OR: 1.15-1.63; test for trend: p < 0.001), whereas cumulative dose of chlorprothixene ≥1500 mg was associated with increased risk of MACE (OR: 1.10-1.85; test for trend: p < 0.001). In conclusion, low-dose chlorprothixene use is associated with increased risk of cardiometabolic adverse events compared with low-dose quetiapine use.

Topics: Cardiovascular Diseases; Chlorprothixene; Cohort Studies; Diabetes Mellitus, Type 2; Humans; Myocardial Infarction; Quetiapine Fumarate; Risk Factors

An 18-year-old man diagnosed with attention-deficit hyperactivity disorder was recently started on quetiapine in addition to regular methylphenidate, which he had been taking for a number of years. He presented with chest pain and inferolateral ST elevation, and underwent urgent coronary angiography, which showed normal coronary arteries. The initial troponin level was raised and an inpatient echocardiogram showed mild left ventricular systolic dysfunction with no evidence of regional wall motion abnormality. Cardiac MRI showed subepicardial late gadolinium enhancement, which was suggestive of myocarditis. Quetiapine and methylphenidate were discontinued and the patient was discharged home after 1 week. He was followed up within 8 weeks with complete recovery and no symptoms.

Topics: Adolescent; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Chest Pain; Diagnosis, Differential; Dibenzothiazepines; Dopamine Uptake Inhibitors; Humans; Male; Methylphenidate; Myocardial Infarction; Myocarditis; Quetiapine Fumarate; Treatment Outcome