The pharmacotherapy of depressive illness in adolescents: an open-label comparison of fluoxetine with imipramine-treated historical controls.

BACKGROUND: This open-label, 6-week clinical trial investigated the response to fluoxetine in medication-naive adolescents hospitalized for treatment of major depression. METHOD: A total of 52 consecutively admitted patients (mean age = 15.7 years) fulfilling Research Diagnostic Criteria for unipolar, nonpsychotic major depression received fluoxetine monotherapy (mean dose = 33.2 mg/day) in conjunction with psychosocial therapies. Outcome was assessed weekly using the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions Scale (CGI). Response in this cohort was compared with that observed in 28 historical controls treated with imipramine (mean dose = 217 mg/day) who were consecutively admitted patients to this same facility and assessed in an identical, standardized, open-label protocol. RESULTS: HAM-D scores decreased by a mean of 13.2 in the fluoxetine group compared with 10.2 in the group receiving imipramine (p<.002). The mean percentage decreases in HAM-D scores in the 2 groups were 54.3% and 41.4%, respectively (p<.003). The percentages of patients classified as responders based on a final CGI score of 2 or less were 48.1% and 17.9%, respectively (p = .009). Medications were generally well tolerated with only 5 patients failing to complete the full 6 weeks of their original treatment. CONCLUSION: In spite of the uncontrolled nature of these data, the findings add to recent evidence suggesting more favorable response to selective serotonin reuptake inhibitors than tricyclics in adolescents with depressive illness.

The pharmacotherapy of depressive illness in adolescence: II. Effects of lithium augmentation in nonresponders to imipramine.

The antidepressant value of lithium augmentation was assessed in a 3-week open trial involving 24 adolescents who remained highly depressed after 6 weeks of treatment with imipramine hydrochloride. Two patients responded dramatically during the first week, with an additional eight patients showing partial improvement during the 3-week trial. The overall magnitude of improvement in depression ratings was significantly greater than in an historical control group of nonresponders who continued to receive imipramine monotherapy during their hospital treatment. Results suggest the potential use of this adjunctive strategy in some tricyclic resistant adolescent depressives, although it appears less efficacious overall in this age group than in adults.

The pharmacotherapy of depressive illness in adolescence: I. An open label trial of imipramine.

The efficacy of imipramine hydrochloride (IMI) for adolescents with major depressive illness meeting Research Diagnostic Criteria (RDC) and DSM-III criteria was assessed in an open-label trial of 35 inpatients. Patients were treated for 6 weeks up to a target dosage of 5 mg/kg/day and assessed weekly by the Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions Improvement scale (CGI). A total of 34 patients in the sample completed the trial, 28 achieving the full target dosage (mean = 222 mg; mean IMI plus desmethylimipramine (DMI) plasma level = 237 ng/ml). Among 24 nondelusional patients, only one third were considered responders based on pattern analysis of the time of onset and persistence of symptom reduction. Among 10 delusional patients, the response rate was 10 percent. Although total IMI plus DMI plasma level did not differ between responders and nonresponders, no responder had a level below 180 ng/ml. In univariate linear regression analysis, no single variable was predictive of response status at 6 weeks. These findings underscore the importance of a comprehensive study of the potency of antidepressant compounds in adolescents and the need for further investigation of psychobiological process mediating drug effects.