Psychotropic use and risk of stroke among patients with bipolar disorders: 10-year nationwide population based study

Objectives: To investigate the association between psychotropic agents (including antipsychotics, antidepressants and mood stabilizers) and risk of stroke among patients with bipolar disorders. Methods: We conducted a disease risk score-matched nested case-control study and identified patients with bipolar disorders (ICD-9 codes: 296.0x, 296.1x, 296.4x, 296.5x, 296.6x, 296.7x, 296.80, 296.81 or 296.89) from the National Health Insurance Research Database in Taiwan. Among them, we identified 1232 cases (981 were ischemic stroke and 251 were hemorrhagic stroke) and 5314 disease risk score-matched controls. Conditional logistic regression model equations were applied to determine the effect of psychotropic agents on stroke risk among patients with bipolar disorders. Results: The results indicated that overall use of psychotropic agents was associated with an increased risk of stroke (adjusted odds ratio [AOR] = 1.82; 95% confidence interval [CI]: 1.56-2.13). When classifying psychotropic agents into antipsychotics, antidepressants and mood stabilizers, respectively, a significant positive association was found for users of antipsychotics (AOR = 1.98; 95% CI = 1.53-2.56), antidepressants (AOR = 1.44; 95% CI = 1.16-1.79), and mood stabilizers (AOR = 1.89; 95% CI = 1.22-2.93). Combined use of psychotropic agents was associated with higher risk of stroke than monotherapy (AOR = 2.62; 95% CI = 1.98-3.45). Discussions: The results support our hypothesis that psychotropic use is associated with increased risk of stroke among patients with bipolar disorders. The stroke risks are higher among patients with polypharmacy than those with monotherapy. These findings warrant further investigation to confirm and replicate the findings using different methodologies and populations, and to mitigate residual confounding.