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.

Recovery and relapse in adolescents with bipolar affective illness: a five-year naturalistic, prospective follow-up.

OBJECTIVE: This study was a 5-year naturalistic prospective follow-up of 54 consecutive admissions of adolescents to a university inpatient service with a diagnosis of bipolar I affective illness. METHOD: Subjects received structured clinical evaluations every 6 months after entry to establish time to recovery and subsequent relapse. Regression models were used to identify predictors of differential course. RESULTS: Rate of recovery varied by polarity of episode at time of entry, with quick recovery observed in subjects with pure mania or mixed states, and a protracted index episode in subjects with pure depression. Multiple relapses were most often seen in subjects with mixed or cycling episodes at intake. CONCLUSIONS: Polarity of illness may have utility in identifying bipolar adolescents with a more recurrent illness. Comparison with adult data suggests that recurrence risks may vary as a function of age at onset or stage of the disease process.

Early childhood attention deficit hyperactivity disorder predicts poorer response to acute lithium therapy in adolescent mania.

We compared the response to acute lithium therapy in 30 adolescents, 13-17 years of age, with mania and a prior history of early childhood attention deficit hyperactivity disorder (ADHD) to a sex- and age-matched control group of adolescent manics without premorbid psychiatric illness. Response to treatment was assessed daily over the course of 28 days using measures of global clinical improvement and severity ratings on the Bech-Rafaelsen Mania Scale (BRMS). BRMS scores decreased by a mean of 24.3 in the subgroup without prior ADHD compared to 16.7 in patients with ADHD (P = 0.0005). The average percent drop in BRMS scores over the study period in these two subgroups was 80.6% and 57.7%, respectively (P = 0.0005). Time to onset of sustained global clinical improvement was also assessed using Kaplan-Meier survival methods and possible covariates of time to improvement were tested in a Cox proportional hazards model. Median time to onset of sustained improvement was lengthened significantly in patients with early ADHD (23 days) compared to those without it (17 days; log rank chi2 = 7.2, P = 0.007). The results suggest that early childhood ADHD defines an important source of heterogeneity in bipolar illness with developmental, clinical, and neuropharmacogenetic implications.