Birmaher, Boris, Waterman, G., Ryan, Neal D., Perel, James, McNabb, Joanne, Balach, Lisa, Beaudry, Mary Beth, Nasr, Farida N., Karambelkar, Jagannath, Elterich, Gertrude, Quintana, Humberto, Williamson, Douglas E., Rao, Uma

Randomized, controlled trial of amitriptyline versus placebo for adolescents with \"treatment-resistant\" major depression

Assessed the response to a serotonergic/noradrenergic tricyclic antidepressant, amitriptyline (AMI), in a group of adolescents with treatment-resistant major depressive disorder (MDD). 27 depressed adolescents admitted to a state hospital underwent a 10-wk randomized, controlled trial with a flexible dose of AMI or placebo. There were no differences between patients taking AMI (13 Ss) and placebo (14 Ss). Both treatment groups showed approximately 70- 80% improvement on the clinical outcome measurements, and 65-70% showed functional improvement. At the end of the protocol, 30% of patients still fulfilled criteria for MDD and had impaired functioning. Patients taking AMI experienced significantly more dry mouth and tachycardia. The final AMI dose was 173.1 mg/day 56.3 mg/day No significant differences were found between AMI and placebo, in part because of the high placebo response rate. Although both treatment groups showed substantial response, at the end of treatment a substantial proportion of patients still had MDD or subsyndromal symptoms of depression. This and other studies of tricyclic antidepressants question the use of this medication as 1st-line treatment for youths with MDD. (PsycINFO Database Record (c) 2007 APA, all rights reserved).

Journal of the American Academy of Child & Adolescent Psychiatry, 37(5) : 527-535

Geller, Barbara, Cooper, Thomas B., Zimerman, Betsy, Frazier, Jeanne, Williams, Marlene, Heath, Janet, Warner, Kathy

Lithium for prepubertal depressed children with family history predictors of future bipolarity: A double-blind, placebo-controlled study

Examined the hypothesis that lithium would be efficacious treatment for prepubertal major depressive disorder (PMDD) in children who also had family history (FH) predictors of future bipolar disorder (BP). A double-blind, placebo-controlled, and pharmacokinetically dosed study of lithium for PMDD with FH predictors of future BP was performed. Random assignment was stratified by FH of BP-I or mania vs loaded/multigenerational (L/M) FH of MDD without BP-I or mania. 17 Ss (aged 6-12 yrs) were randomized to active and 13 to placebo; 80% had FH of BP-I or mania (40% of parents had BP-I or mania); and 20% had FH of L/M MDD. Using both intent to treat with last observation carried forward and completer analyses, there were no significant differences on continuous or categorical measures between active and placebo groups. (PsycINFO Database Record (c) 2007 APA, all rights reserved).

Journal of Affective Disorders, 51(2) : 165- 175

Emslie, G. J., Rush, A. J., Weinberg, W. A.

Fluoxetine decreased depressive symptoms in children and adolescents with nonpsychotic major depressive disorder

Evidence-Based Medicine, 3(4) : 105

Harrington, R., Whittaker, J., Shoebridge, P., Campbell, F.

Systematic review of efficacy of cognitive behaviour therapies in childhood and adolescent depressive disorder

Objective: To determine whether cognitive behaviour therapy is an effective treatment for childhood and adolescent depressive disorder. Design: Systematic review of six randomised trials comparing the efficacy of cognitive behaviour therapy with inactive interventions in subjects aged 8 to 19 years with depressive disorder. Main outcome measure: Remission from depressive disorder. Results: The rate of remission from depressive disorder was higher in the therapy group (129/208; 62%) than in the comparison group (61/168; 36%). The pooled odds ratio was 3.2 (95% confidence interval 1.9 to 5.2), suggesting a significant benefit of active treatment. Most studies, however, were based on relatively mild cases of depression and were of only moderate quality. Conclusions: Cognitive behaviour therapy may be of benefit for depressive disorder of moderate severity in children and adolescents. It cannot, however, yet be recommended for severe depression. Definitive large trials will be required to determine whether the results of this systematic review are reliable.

British Medical Journal, 316(7144) : 1559- 1563

Klein, R. G., Mannuzza, S., Koplewicz, H. S., Tancer, N. K., Shah, M., Liang, V., Davies, M.

Adolescent depression: Controlled desipramine treatment and atypical features

The study was designed to test the efficacy of desipramine in adolescents with major depression (MDD). In addition, we assessed the presence of atypical features of MDD, consisting of mood reactivity and two of four associated features (rejection sensitivity, hyperphagia, hypersomnia, and leaden paralysis). Patients were randomized to desipramine (DMI) or placebo for 6 weeks, provided they failed to improve (e.g., meeting MDD criteria and a Hamilton Depression Scale score [less-than or equal to]18) after 2 weeks on single blind placebo. Of 94 adolescents (ages 13-18) who were diagnosed as having MDD, 64 entered the study and 62 received placebo for 2 weeks. Of these, 45 were randomized to DMI or placebo. Completer analyses did not reveal significant improvement for the active treatment compared to the placebo. A large proportion of adolescents responded to placebo (50%), suggesting the need for very large samples to detect differential treatment efficacy, should it exist. A relatively high rate of atypical depression was observed (47% in the 64 patients entered). In view of the demonstrated specificity of monoamine oxidase inhibitor efficacy in adults with atypical features of MDD, this clinical subtype may have relevance to future investigation of therapeutic interventions in adolescent MDD.

Depression & Anxiety, 7(1) : 15- 31

Reinecke, Mark A., Ryan, Nancy E., DuBois, David L.

Cognitive-behavioral therapy of depression and depressive symptoms during adolescence: A review and meta-analysis

Critically reviews the literature on cognitive-behavioral therapy with depressed and dysphoric adolescents. A meta-analysis was conducted to assess the effectiveness of these approaches and the stability of therapeutic gains. 14 posttreatment-control comparisons and 10 followup-control comparisons resulted from 6 studies containing 217 Ss (children, adolescents, and adults). Results suggest the short- and long-term effectiveness of cognitive-behavioral approaches for treating depressive symptoms with this population. (PsycINFO Database Record (c) 2007 APA, all rights reserved).

Journal of the American Academy of Child & Adolescent Psychiatry, 37(1) : 26- 34

Vostanis, P., Feehan, C., Grattan, E.

Two-year outcome of children treated for depression

Fifty-four children and adolescents (age 8-17) were assessed two years after a clinical intervention trial of cognitive-behavioural vs. non-focused treatment for depression. Eleven (20.4%) subjects fulfilled criteria for depression, while 21 (38.9%) reported significant depressive symptoms during the previous year. Seventeen young people (31.5%) had a psychiatric disorder (including depression). Overall, the sample maintained the improvement since the termination of treatment, without detecting specific treatment effects. Presence of depression at two-year follow-up was best predicted by self- esteem ratings before and after treatment, and co-morbidity at post- treatment. Depression in young life carries a high risk of recurrence, despite initial remission. Continuation or preventative treatment for young people at risk of relapse needs development and evaluation.

European Child & Adolescent Psychiatry., 7(1) : 12- 18

Weisz, J. R., Thurber, C. A., Proffitt, V. D., Sweeney, L., LeGagnoux, G. L.

Brief treatment of mild-to-moderate child depression using Primary and Secondary Control Enhancement Training

Elementary school children with mild-to-moderate depressive symptoms were randomly assigned to a control group or an 8- session Primary and Secondary Control Enhancement Training program. The program focused on (a) primary control (changing objective conditions to fit one's wishes; e.g., through activity selection and goal attainment) and (b) secondary control (changing oneself to buffer the impact of objective conditions; e.g., altering depressogenic thinking, practicing mood-enhancing cognitions). At immediate posttreatment and 9-month follow-up, the treatment group showed greater reductions than the control group in depressive symptomatology on the Children's Depression Inventory and the Revised Children's Depression Rating Scale, and treated children, more than controls, shifted' from above to within the normal range on both measures. Future research is needed to test treatment effects with severely depressed youths.

Journal of Consulting & Clinical Psychology., 65(4) : 703-707

Sallee, F. R., Vrindavanam, N. S., Deas-Nesmith, D., Carson, S. W., Sethuraman, G.

Pulse intravenous clomipramine for depressed adolescents: Double-blind, controlled trial.[see comment]

OBJECTIVE: Major depressive disorder in adolescents is characterized as treatment resistant, but a previous open-label trial of pulse intravenous clomipramine demonstrated rapid relief of depressive symptoms. In the present study a single intravenous dose of clomipramine (200 mg) was compared with saline placebo in a randomized controlled trial for depressed adolescents. The hypothesis was that adolescents who were treated with pulse clomipramine would exhibit lower scores on the Hamilton Depression Rating Scale at endpoint than would adolescents who received saline and that clomipramine would be superior to saline in terms of antidepressant response. METHOD: Sixteen nonsuicidal outpatient adolescents (mean age = 16.2 years, SD = 1.0) who met the DSM- III-R criteria for major depression (score on 21-item Hamilton scale, > or = 18) were randomly assigned to receive either clomipramine (200 mg i.v., N = 8) or saline (N = 8). Assessments of depression severity were completed 36 hours and 6 days thereafter. RESULTS: The adolescents who received pulse clomipramine treatment demonstrated significant decreases in Hamilton depression scores from baseline at 6 days but not at 36 hours. A similar decrease from baseline was found in Clinical Global Impression severity at 6 days but not 36 hours. Seven of the clomipramine-treated patients and three of the saline-treated patients had drops of 50% or more from baseline in Hamilton depression score. CONCLUSIONS: Pulse clomipramine (200 mg i.v.) is associated with dramatic reduction in depressive symptoms at day 6 after infusion, which is significantly different from the effect of placebo.

American Journal of Psychiatry, 154(5) : 668-73

Mandoki, M. W., Tapia, M. R., Tapia, M. A., Sumner, G. S., Parker, J. L.

Venlafaxine in the treatment of children and adolescents with major depression

Major depression is commonly found in the child and adolescent population. Venlafaxine, a new antidepressant, has been used successfully in adults; however, its use in children and adolescents has been very limited. This study evaluated the efficacy and side effect profile of venlafaxine in the treatment of depression in children and adolescents. In a double-blind, placebo-controlled, 6-week study, 33 subjects between the ages of 8 and 17, who met DSM-IV criteria for major depression, were treated with either venlafaxine and therapy or placebo and therapy. Patient progress data were obtained by weekly rating assessments. Data on side effects were also obtained weekly. The statistical analysis indicated a significant improvement over time, but it could not be attributed to venlafaxine drug therapy. These findings are consistent with other studies where the efficacy of antidepressants in the treatment of major depression in this age population remains unproven. Low dosage and short length of treatment may account for the lack of efficacy. The findings did, however, suggest a low side-effect profile. Further studies are recommended to assess efficacy and to corroborate its safety in children and adolescents.

Psychopharmacology Bulletin, 33(1) : 149-54

Emslie, Graham J., Rush, John, Weinberg, Warren A., Kowatch, Robert A., Hughes, Carroll W., Carmody, Tom, Rintelmann, Jeanne

A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression

Evaluated the efficacy, safety, and tolerability of fluoxetine treatment for children with nonpsychotic major depressive disorders (NMDD). 96 outpatients (aged 7-17 yrs) meeting Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) criteria for NMDD participated in a randomized, double-blind, placebo-controlled study. 48 of the patients were randomized to fluoxetine treatment and the other 48 received placebo. The 2 major outcome measures were the Clinical Global Impressions (CGI) scale and the Children's Depression Rating Scale--Revised (CDRS--R) and were administered weekly throughout the 8-wk study. 27 Ss receiving fluoxetine and 16 receiving placebo were rated as \"much\" or \"very much\" improved according to the CGI. The CDRS--R scores were significantly lower for the fluoxetine group at week 5. Overall, results suggest that fluoxetine was significantly more effective than placebo in the acute phase treatment of NMDD, but complete remission was rare. (PsycINFO Database Record (c) 2007 APA, all rights reserved).

Archives of General Psychiatry, 54(11) : 1031-1037

Beardslee, W. R., Versage, E. M., Wright, E. J., Salt, P., Rothberg, P. C., Drezner, K., Gladstone, T. R.

Examination of preventive interventions for families with depression: Evidence of change

Thirty-seven families who had a child between the ages of 8 and 15 (mean age = 12.0 years) and had at least one parent, who had experienced a recent episode of affective disorder were assigned randomly to one of two psychoeducational interventions. The interventions (clinician-facilitated or lecture-group discussion) were designed to prevent childhood depression and related problems through decreasing the impact of related risk factors and encouraging resiliency-promoting behaviors and attitudes. They were similar in content but differed in the level of the children's involvement and the degree to which the families' individual life experiences were linked to the educational material. Assessments included standard diagnostic and social functioning instruments and interviews designed specifically for this project to assess behavior and attitude change. Each parent and child was individually assessed by separate assessors who were blind to information about the other family members. Parent participants in both groups reported being satisfied with the intervention. Clinician group participants reported a significantly larger number of overall changes, as well as higher levels of change regarding communications about the illness with their children and increased understanding by the children of their illness. Significantly more children in the clinician group also reported they gained a better understanding of parental affective illness as a result of their participation in the project.

Development & Psychopathology, 9(1) : 109- 30