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In their report on age effects on risk of antidepressant treatment–associated mania, Martin et al1 found that children, adolescents, and young adults treated for depressive or anxiety disorders showed an increased risk of new-onset mania at ages 15 to 25 years. Rates of “conversion” to bipolar disorder (new mania) were lowest in children aged 5 to 9 years and similarly intermediate in those aged 10 to 14 years and 25 to 29 years. They also found a nearly 2-fold greater overall risk of mania with tricyclic antidepressants (TCAs) (hazard ratio vs no antidepressant exposure, 3.9) than with serotonin reuptake inhibitors (SRIs) (hazard ratio, 2.1).
We reanalyzed their data (Table 3)1 (p779) concerning risks of mania with SRIs, TCAs, all antidepressants, and no antidepressant treatment vs age. The findings (Figure) indicate an elevated risk of new mania at ages 5 to 19 years with any antidepressant treatment and a particularly large difference in risk between antidepressant-treated and untreated patients (drug effect) at ages 5 to 14 years. This major difference between antidepressant-exposed and unexposed juveniles is consistent with the possibility that bipolar disorder more often had been identified already among adult patients excluded from the study.
Risk (percentage of patients with depressive or anxiety disorders) of developing mania vs age during treatment with tricyclic antidepressants (TCAs), serotonin reuptake inhibitors (SRIs), any antidepressant (ADD), or no ADD. Data are adapted from Martin et al,1 with standard errors.
Another striking observation is that an expected greater risk of mania with TCAs than SRIs, as reported in adults,2 was found only in juveniles older than 14 years (Figure), suggesting that SRIs may have a particularly high risk of inducing mania in children and young adolescents. For subjects aged 5 to 14 vs 15 to 29 years, there was a large difference in risk of mania with SRIs (15.1% vs 8.0%; risk ratio, 1.87 [95% confidence interval, 1.71-2.05]; z = 13.8; P<.001) but not TCAs (11.4% vs 13.3%; risk ratio, 0.86 [95% confidence interval, 0.69-1.07]; z = 1.34; P = .18). This relatively high risk of mania in children given an SRI accords with our recent study of risk factors associated with mania in children. We found that SRIs were at least as likely as TCAs to be associated with new-onset mania within 30 days and that both were somewhat more risky than stimulants.3
These findings, taken together, suggest that health care professionals prescribing antidepressants for children and young adolescents should be particularly alert to what may well be greater risks of inducing mania with SRIs in young persons with as yet unrecognized or latent juvenile bipolar disorder than among older adolescents and adults. When assessing children or young adolescents with depressive, anxiety, or attention disorders, risk factors for juvenile bipolar illness, such as family history, should routinely be considered.4
Correspondence: Dr Baldessarini, Mailman Research Center, McLean Division of Massachusetts General Hospital, 115 Mill St, Belmont, MA 02478-9106 (rjb@mclean.org).
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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