EVALUATING CLINICAL-RESPONSE OF OPEN NORTRIPTYLINE PHARMACOTHERAPY INADOLESCENT MAJOR DEPRESSION

Adolescents with major depressive disorder (N = 25) were treated with nortriptyline 100 mg for 6 to 10 weeks. Clinical change was assessed b y three treatment outcome measures: the Schedule for Affective Disorde rs and Schizophrenia (K-SADS-III-R) (to assess syndromal recovery, i.e ., no longer fulfilling diagnostic criteria for the disorder), the sel f-rated Beck Depression Inventory, and a clinician-rated 17-item Depre ssion Scale (derived from the K-SADS-III-R). At 6 weeks, recovery rate s for full response were 44% to 57%, for partial response were 26% to 32%, and for nonresponse were 12% to 28%. Better outcome was not assoc iated with concurrent treatment (hospital or outpatient), endogenous o r nonendogenous status, or pretreatment depression severity. A signifi cantly greater number of full and partial responders had plasma nortri ptyline levels in the adult range of 50-150 ng/ml. None of the respons e measures, when analyzed as continuous variables, were curvilinearly associated with plasma nortriptyline levels, a finding which does not support the therapeutic window hypothesis. The 17 adolescents who were treated for 10 weeks continued to improve on all three outcome measur es (syndrome, p < 0.07; Beck, p < 0.05; 17-Item, p < 0.004) relative t o their response at 6 weeks. By 10 weeks, all three measures suggested clinical improvement, but no conclusions about efficacy can be offere d in view of the open-label design, absence of placebo controls, diagn ostic subtype heterogeneity, small sample size, and concurrent treatme nts. These data suggest that apparent improvement in adolescent major depressive disorder may vary, depending on treatment outcome criteria, plasma nortriptyline level, and treatment duration. Clinical recovery appears more rapid when treatment response is defined by the clinicia n-rating (17-Item Depression Scale) and slower when defined by self-ra ting (Beck Depression Inventory) or by diagnostic status (syndromal cr iteria). The clinician-rated scale may be more sensitive to early impr ovements in adolescents, as in adults. Extending treatment from 6 to 1 0 weeks increased the response rate by about 50%, so a 10-week trial o f nortriptyline might be clinically indicated before nonresponse statu s in adolescents is established.