Comparison of Long-Acting Injectable and Oral Antipsychotics in Bipolar Disorder

OBJECTIVE: Long-acting injectable antipsychotics (LAIAs) can improve adherence, but their optimal use in bipolar disorder needs to be further explored. This study compared LAIAs and oral antipsychotics with respect to health care utilization, illness relapse, and safety in individuals with bipolar disorder. METHODS: A self-controlled case series study was conducted using data from Hong Kong's electronic health records on individuals with bipolar disorder who received prescriptions for both LAIAs and oral antipsychotics during the period of January 1, 2004, through December 31, 2023. Outcomes included measures of health care utilization, illness relapse, and safety. Adjusted incidence rate ratios (aIRRs) for LAIA versus oral antipsychotic treatment periods were estimated using conditional Poisson regression. RESULTS: Among 17,841 people with bipolar disorder, 2,086 (11.7%) received prescriptions for both LAIAs and oral antipsychotics. Compared with oral antipsychotics, LAIAs were associated with statistically significantly lower risks of all-cause emergency department visits (aIRR=0.85, 95% CI=0.81, 0.89), all-cause hospitalizations (aIRR=0.79, 95% CI=0.73, 0.85), psychiatric hospitalizations (aIRR=0.67, 95% CI=0.61, 0.74), hospitalizations for manic episodes (aIRR=0.51, 95% CI=0.44, 0.59), and hospitalizations for mixed episodes (aIRR=0.31, 95% CI=0.14, 0.66). No statistically significant difference was found for hospitalizations for depressive episodes (aIRR=1.34, 95% CI=0.94, 1.93), nonpsychiatric hospitalizations (aIRR=0.97, 95% CI=0.87, 1.08), or cardiovascular hospitalizations (aIRR=0.84, 95% CI=0.62, 1.14). LAIAs were initially associated with an increased risk of extrapyramidal symptoms (aIRR=2.95, 95% CI=1.40, 6.22), but this difference was not statistically significant beyond 90 days of treatment. CONCLUSIONS: LAIAs were associated with substantially less health care utilization and fewer relapses of manic and mixed episodes, and they were not associated with increased risk of nonpsychiatric hospitalizations, notably for cardiovascular disease. These findings support the use of LAIAs for bipolar disorder, with close monitoring for extrapyramidal symptoms during initiation.