Cardiovascular and cerebrovascular risk factors and events associated with second-generation antipsychotic compared to antidepressant use in a non-elderly adult sample: results from a claims-based inception cohort study

This is a study of the metabolic and distal cardiovascular/cerebrovascular outcomes associated with the use of second-generation antipsychotics (SGAs) compared to antidepressants (ADs) in adults aged 18-65 years, based on data from Thomson Reuters MarketScan (R) Research Databases 2006-2010, a commercial U.S. claims database. Interventions included clinicians' choice treatment with SGAs (allowing any comedications) versus ADs (not allowing SGAs). The primary outcomes of interest were time to inpatient or outpatient claims for the following diagnoses within one year of SGA or AD discontinuation: hypertension, ischemic and hypertensive heart disease, cerebrovascular disease, diabetes mellitus, hyperlipidemia, and obesity. Secondary outcomes included the same diagnoses at last follow-up time point, i.e., not censoring observations at 365 days after SGA or AD discontinuation. Cox regression models, adjusted for age, gender, diagnosis of schizophrenia and mood disorders, and number of medical comorbidities, were run. Among 284,234 individuals, those within one year of exposure to SGAs versus ADs showed a higher risk of essential hypertension (adjusted hazard ratio, AHR=1.16, 95% CI: 1.12-1.21, p<0.0001), diabetes mellitus (AHR=1.43, CI: 1.33-1.53, p<0.0001), hypertensive heart disease (AHR=1.34, CI: 1.10-1.63, p<0.01), stroke (AHR=1.46, CI: 1.22-1.75, p<0.0001), coronary artery disease (AHR=1.17, CI: 1.05-1.30, p<0.01), and hyperlipidemia (AHR=1.12, CI: 1.07-1.17, p<0.0001). Unrestricted follow-up results were consistent with within one-year post-exposure results. Increased risk for stroke with SGAs has previously only been demonstrated in elderly patients, usually with dementia. This study documents, for the first time, a significantly increased risk for stroke and coronary artery disease in a non-elderly adult sample with SGA use. We also confirm a significant risk for adverse metabolic outcomes. These findings raise concerns about the longer-term safety of SGAs, given their widespread and chronic use.