Moderators of fluoxetine treatment response for children and adolescents with comorbid depression and substance use disorders.

Our recent 8-week, randomized, placebo-controlled trial of fluoxetine in adolescents (ages 12-17 years) with comorbid depression and substance use disorder (SUD) did not detect a significant antidepressant treatment effect. The purpose of this secondary analysis was to explore moderators of the effect of fluoxetine in this sample. Static moderators measured at baseline were depression chronicity and hopelessness severity; time-varying moderators measured at baseline and weekly during the 8-week trial period were alcohol and marijuana use severity. Treatment effects on depression outcomes were examined among moderating subgroups in random effects regression models. Subjects assigned to fluoxetine treatment with chronic depression at baseline (p = .04) or no more than moderate alcohol use during the trial (p = .04) showed significantly greater decline in depression symptoms in comparison to placebo-assigned subgroups. The current analysis suggests that youth with chronic depression and no more than moderate alcohol consumption are likely to respond better to treatment with fluoxetine compared with placebo than youth with transient depression and heavy alcohol use.

The short-term safety and efficacy of fluoxetine in depressed adolescents with alcohol and cannabis use disorders: a pilot randomized placebo-controlled trial.

BACKGROUND: The objective of this study was to examine whether fluoxetine was superior to placebo in the acute amelioration of depressive symptomatology in adolescents with depressive illness and a comorbid substance use disorder. METHODS: Eligible subjects ages 12-17 years with either a current major depressive disorder (MDD) or a depressive disorder that were also suffering from a comorbid substance-related disorder were randomized to receive either fluoxetine or placebo in this single site, 8-week double-blind, placebo-controlled study. The primary outcome analysis was a random effects mixed model for repeated measurements of Children's Depression Rating Scale-Revised (CDRS-R) scores compared between treatment groups across time. RESULTS: An interim analysis was performed after 34 patients were randomized. Based on the results of a futility analysis, study enrollment was halted. Twenty-nine males and 5 females were randomized to receive fluoxetine (n = 18) or placebo (n = 16). Their mean age was 16.5 (1.1) years. Overall, patients who received fluoxetine and placebo had a reduction in CDRS-R scores. However, there was no significant difference in mean change in CDRS-R total score in those subjects treated with fluoxetine and those who received placebo (treatment difference = 0.19, S.E. = 0.58, F = 0.14, p = .74). Furthermore, there was not a significant difference in rates of positive urine drug toxicology results between treatment groups at any post-randomization visit (F = 0.22, df = 1, p = 0.65). The main limitation of this study is its modest sample size and resulting low statistical power. Other significant limitations to this study include, but are not limited to, the brevity of the trial, high placebo response rate, limited dose range of fluoxetine, and the inclusion of youth who met criteria for depressive disorders other than MDD. CONCLUSION: Fluoxetine was not superior to placebo in alleviating depressive symptoms or in decreasing rates of positive drug screens in the acute treatment of adolescents with depression and a concomitant substance use disorder.

Initiation of stimulant and antidepressant medication and clinical presentation in juvenile bipolar I disorder.

OBJECTIVES: The primary purpose of this study was to examine the extent to which the initiation of stimulant and antidepressant medication was associated with the subsequent onset of juvenile bipolar I disorder (BP I). Another aim was to investigate differences in clinical presentation between youths prescribed stimulant or antidepressant medication before and after the onset of juvenile BP I disorder. METHODS: Youths between the ages of 5 and 17 years meeting full, unmodified DSM-IV diagnostic symptom criteria for BP were included in this study. Data regarding the age of onset of BP I, psychiatric comorbidities, and current symptoms of mania and depression were obtained. Medication history was recorded as part of the assessment interview with parents and youths. RESULTS: Of the 245 youths with BP I, 65% (n = 160) were treated with stimulant medication; 32% (56/173) were treated after the onset of BP I, and 19% (32/173) were treated before the onset of BP I. Forty-six percent (113/245) were treated with antidepressant medication; 33% (67/206) were treated after the onset of BP I, and 3% (7/206) were treated before the onset of BP I. Patients who were treated with stimulants after the onset of BP I were significantly more likely to be younger (p < 0.0001). Patients who were treated with antidepressants before the onset of BP I were significantly more likely to be older and to have lower levels of mania on the Young Mania Rating Scale at assessment (p < 0.01). CONCLUSIONS: Data from this retrospective case series do not support the association between initial stimulant or antidepressant use and the onset of BP I or presenting symptoms of depression or manic symptoms.