Age effects on antidepressant-induced manic conversion

Background: Antidepressant drug therapy can precipitate mania in vulnerable individuals, but little is known about the effects of age on this phenomenon. Objective: To pharmacoepidemiologically evaluate the risk of conversion to mania by antidepressant class and patient age. Design, Setting, and Patients: Using an administrative national database of more than 7 million privately insured individuals, linked outpatient and pharmacy claims were analyzed for mental health users aged 5 to 29 years (N=87920). Main Outcome Measures: The proportion and cumulative hazard of manic conversion were analyzed by antidepressant class and subject age among children, adolescents, and young adults with an anxiety or nonbipolar mood disorder in the United States between January 1, 1997, and December 31, 2001. Manic conversion was defined as a new diagnosis of bipolar illness. Results: During median follow-up of 41 weeks (range, 8-251 weeks), manic conversion occurred in 4786 patients (5.4%). Multivariate analyses using time-dependent Cox proportional hazards models indicated that an increased risk of manic conversion was associated with antidepressant category vs no antidepressant exposure (hazard ratios: 2.1 for selective serotonin reuptake inhibitors, P<.001; 3.8 for other antidepressants, P<.001; and 3.9 for tricyclic antidepressants, P = .002). Antidepressant x age interactions revealed inverse age effects for selective serotonin reuptake inhibitors and other antidepressants (beta = -.05; P<.001 for both) but not for tricyclic antidepressants (beta = -.02; P = .25). Peripubertal children exposed to antidepressants were at highest risk of conversion (number needed to harm: 10 [95% confidence interval, 9-12] among 10- to 14-year-olds vs 23 [95% confidence interval, 21-25] among 15- to 29-year-olds). Conclusions: Patient age is an effect modifier on the risk of antidepressant-associated manic conversion. Treatment with antidepressants is associated with highest conversion hazards among children aged 10 to 14 years.