Nevertheless, the idea that a treatment for a circumscribed period of time results in long-term changes in function of the serotonin system, even without clear behavioral changes, is unsettling. This study should be replicated with behavioral and PET data in primates obtained prior to and after treatment, with a larger number of monkeys, and with measures of the noradrenergic system. In humans, follow-up studies of adolescents treated with antidepressants compared with psychotherapy should be conducted to look for any specific, enduring changes in brain function and receptor binding and whether those changes are related to changes in behavior and long-term outcome. We should also learn, in controlled studies, to what extent medication compared with psychotherapy protects against recurrent depression. In adults, some evidence indicates that depressed patients treated with cognitive-behavioral therapy (CBT) are less likely to relapse than patients treated with antidepressants (4), but the existing evidence in adolescents, at least with relatively brief interventions, does not support a similar protective effect of CBT compared with antidepressants (5, 6). The British National Institute for Health and Care Excellence guidelines, with regard to concern about suicidal events and antidepressants in adolescents, firmly recommend a trial with psychotherapy before the use of medication. However, given the much slower response to CBT for adolescent depression than to antidepressants that was found in the Treatment of Adolescent Depression Study, American guidelines recommend antidepressants as a first-line treatment for adolescent depression (7, 8). It is also important not to paint recommendations about antidepressant use in adolescents with too broad a brush, since the risk-benefit ratio is even more favorable for the treatment of anxiety than for the treatment of depression, as a result of greater efficacy (9).