Melvin, Glenn A., Tonge, Bruce J., King, Neville J., Heyne, David, Gordon, Michael S., Klimkeit, Ester

A comparison of cognitive-behavioral therapy, sertraline, and their combination for adolescent depression

OBJECTIVE: To evaluate cognitive- behavioral therapy, antidepressant medication alone, and combined CBT and antidepressant medication in the treatment of depressive disorders in adolescents. METHOD: Seventy-three adolescents (ages 12-18 years) with a primary diagnosis of DSM-IV major depressive disorder, dysthymic disorder, or depressive disorder not otherwise specified were randomly allocated to one of three treatments. Treatment outcome measures were administered before and after acute treatment, and at a 6-month follow-up. Depression diagnosis was the primary outcome measure; secondary measures were self- and other report and clinician rating of global functioning. The trial was conducted at three community-based clinics between July 2000 and December 2002. Data analyses used an intent-to-treat strategy. RESULTS: Following acute treatment, all treatment groups demonstrated statistically significant improvement on outcome measures (depressive diagnosis, Reynolds Adolescent Depression Scale, Revised Children's Manifest Anxiety Scale, Suicidal Ideation Questionnaire), and improvement was maintained at follow-up. Combined cognitive-behavioral therapy and antidepressant medication was not found to be superior to either treatment alone. Compared with antidepressant medication alone, participants receiving cognitive-behavioral therapy alone demonstrated a superior acute treatment response (odds ratio = 6.86; 95% confidence interval 1.12-41.82). Although cognitive-behavioral therapy was found to be superior to antidepressant medication alone for the acute treatment of mild to moderate depression among youth, this may have stemmed from the relatively low dose of sertraline used. CONCLUSIONS: All treatments led to a reduction in depression, but the advantages of a combined approach were not evident.

Journal of the American Academy of Child & Adolescent Psychiatry, 45(10) : 1151- 61

March, John S., Klee, Brian J., Kremer, Charlotte M.

Treatment benefit and the risk of suicidality in multicenter, randomized, controlled trials of sertraline in children and adolescents

Objective: The aim of this study was to examine the balance between the benefits of treatment and the risk of suicidality in children and adolescents in multicenter, randomized, controlled trials of sertraline versus placebo. Method: The published literature was searched for multicenter, randomized, placebo-controlled trials of sertraline for pediatric mental disorders. Four trials were identified: Two (pooled) in pediatric major depressive disorder (MDD; Wagner 2003) and two in obsessive-compulsive disorder (OCD; March et al. 1998; POTS Team 2004). Using intent-to-treat (ITT) analysis populations, the authors calculated the number needed to treat (NNT) for response and remission and the number needed to harm (NNH) for suicidality, and their ratio, for each clinical trial. Results: NNTs ranged from 2 to 10, indicating clinically meaningful benefits. Benefit was greater for OCD than for MDD, and for adolescents as compared with children in MDD. No age effect was apparent for OCD. Suicidality was reported in 8 patients (5 assigned to sertraline and 3 assigned to placebo). All but 1 (a placebo-treated patient in the Pfizer OCD trial) were enrolled in the sertraline MDD trial. The NNH for suicidality in MDD was 64. Treatment emergent suicidality was more common in children (NNH 28.7) than in adolescents (NNH 706.3). Because no patient developed suicidality in sertraline- treated OCD patients, the NNH for sertraline in OCD approaches infinity. Conclusions: With the stipulation that doctor and patient preferences necessarily play a critical role in the choice of treatment, NNT to NNH ratios indicate a positive benefit-to-risk ratio for sertraline in adolescents with MDD and in patients of all ages with OCD. (PsycINFO Database Record (c) 2007 APA, all rights reserved) (journal abstract).

Journal of Child & Adolescent Psychopharmacology, 16(1-2) : 91-102

Loo, Colleen, McFarquhar, Tara, Walter, Garry

Transcranial magnetic stimulation in adolescent depression

OBJECTIVE: There are few safe and effective biological treatments for major depression in adolescents. We aimed to report the use of repetitive transcranial magnetic stimulation (rTMS) as a treatment for adolescents with this condition. METHODS: The first two subjects in a double-blind, sham-controlled trial of rTMS that is evaluating the efficacy and safety of rTMS in depressed adolescents are described. Clinical response was assessed at baseline and at the end of each week. The following scales were used: Montgomery-Asberg Depression Rating Scale, Clinical Global Impression-Severity Scale, Beck Depression Inventory and Centre for Epidemiological Studies - Depression - Child Scale. A battery of cognitive tests was also used at several intervals to measure potential change in neuropsychological functioning. RESULTS: Random allocation of both subjects was to active treatment. Both subjects improved to a clinically significant degree with rTMS treatment and reported no adverse effects. Neuropsychological testing did not demonstrate any deterioration in the domains of functioning tested. CONCLUSIONS: Repetitive transcranial magnetic stimulation shows early promise as a treatment for major depression in adolescents. Well-designed, sham-controlled studies are now indicated to test the efficacy and safety of rTMS in these patients.

Australasian Psychiatry, 14(1) : 81- 5

Hammerness, Paul G., Vivas, Fe M., Geller, Daniel A.

Selective serotonin reuptake inhibitors in pediatric psychopharmacology: A review of the evidence

Journal of Pediatrics, 148(2) : 158- 65

Kennard, B.,

Remission and residual symptoms after short-term treatment in the Treatment of Adolescents with Depression Study (TADS)

OBJECTIVE: To ascertain remission rates in depressed youth participating in the Treatment for Adolescents With Depression Study (TADS), a multisite clinical trial that randomized 439 adolescents with major depressive disorder (MDD) to a 12-week treatment of fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or clinical management with pill placebo (PBO). METHOD: Using an end-of-treatment Children's Depression Rating Scale-Revised (CDRS-R) total score of 28 or below as the criterion for remission, rates of remission were examined with logistic regression, controlling for site. Loss of MDD diagnosis and residual symptoms in responders (defined as Clinical Global Impressions-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) were also examined across treatment groups. RESULTS: After 12 weeks of treatment, 102 (23%) of 439 youths had reached remission. The remission rate was significantly higher in the COMB group (37%) relative to the other treatment groups (FLX, 23%; CBT, 16%; PBO, 17%), with odds ratios of 2.1 for COMB versus FLX, 3.3 for COMB versus CBT, and 3.0 for COMB versus PBO. In addition, 71% of subjects across treatment groups no longer met criteria for MDD at the end of acute treatment. Fifty percent of the youths who responded by CGI-I criteria continued to have residual symptoms, such as sleep or mood disturbances, fatigue, and poor concentration. CONCLUSIONS: The combination of FLX and CBT was superior to both monotherapy and PBO in terms of remission rates, but overall rates of remission remain low and residual symptoms are common at the end of 12 weeks of treatment. Copyright 2006 copyright American Academy of Child and Adolescent Psychiatry.

Journal of the American Academy of Child & Adolescent Psychiatry, 45(12) : 1404- 1411

Jorm, Anthony F., Allen, Nicholas B., O'Donnell, Colin P., Parslow, Ruth A., Purcell, Rosemary, Morgan, Amy J.

Effectiveness of complementary and self-help treatments for depression in children and adolescents

OBJECTIVE: To review the evidence for the effectiveness of complementary and self-help treatments for depression in children and adolescents. DATA SOURCES: Systematic literature search using PubMed, PsycINFO and the Cochrane Library for 131 treatments up to February 2006. STUDY SELECTION: There were 13 treatments that had been evaluated in intervention studies. DATA EXTRACTION: Studies on each treatment were reviewed by one author and checked by a second. A consensus was reached for level of evidence. DATA SYNTHESIS: Relevant evidence was available for glutamine, S-adenosylmethionine, St John's wort, vitamin C, omega-3 fatty acids, light therapy, massage, art therapy, bibliotherapy, distraction techniques, exercise, relaxation therapy and sleep deprivation. However, the evidence was limited and generally of poor quality. The only treatment with reasonable supporting evidence was light therapy for winter depression. CONCLUSIONS: Given that antidepressant medication is not recommended as a first line treatment for children and adolescents with mild to moderate depression, and that the effects of psychological treatments are modest, there is a pressing need to extend the range of treatments available for this age group. [References: 49]

Medical Journal of Australia, 185(7) : 368-72

Horowitz, Jason L., Garber, Judy

The prevention of depressive symptoms in children and adolescents: A meta-analytic review

Research on the prevention of depressive symptoms in children and adolescents was reviewed and synthesized with meta-analysis. When all 30 studies were included, selective prevention programs were found to be more effective than universal programs immediately following intervention. Both selective and indicated prevention programs were more effective than universal programs at follow-up, even when the 2 studies with college students were excluded. Effect sizes for selective and indicated prevention programs tended to be small to moderate, both immediately postintervention and at an average follow-up of 6 months. Most effective interventions are more accurately described as treatment rather than prevention. Suggestions for future research include testing potential moderators (e.g., age, gender, anxiety, parental depression) and mechanisms, designing programs that are developmentally appropriate and gender and culturally sensitive, including longer follow-ups, and using multiple measures and methods to assess both symptoms and diagnoses. Copyright 2006 APA, all rights reserved.

Journal of Consulting & Clinical Psychology, 74(3) : 401- 15

Kratochvil, C., Emslie, G., Silva, S., McNulty, S., Walkup, J., Curry, J., Reinecke, M., et-al

Acute time to response in the Treatment for Adolescents with Depression Study (TADS)

OBJECTIVE: To examine the time to response for both pharmacotherapy and psychotherapy in the Treatment for Adolescents with Depression Study (TADS). METHOD: Adolescents (N = 439, ages 12 to 17 years) with major depressive disorder were randomized to fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or pill placebo (PBO). Defining response as very much improved or much improved on the Clinical Global Impression- Improvement Scale (CGI-I), survival analyses using Cox proportional hazards models, and Kaplan-Meier curves were conducted to evaluate time to first response and time to stable response for subjects receiving pharmacotherapy (COMB, FLX, PBO) as well as for subjects receiving CBT (COMB, CBT). Direct comparisons between pharmacotherapy and CBT were not made because of differences in visit schedules. RESULTS: Based on pharmacotherapist CGI-I scores, COMB and FLX showed faster onset of benefit than PBO on time to response and time to stable response (p < .001), and COMB was faster than FLX on time to stable response (p = .034). The probability of sustained early response was approximately threefold greater for COMB than PBO, twofold greater for FLX than PBO, and 1.5-fold greater for COMB than FLX. On the psychotherapist CGI-I scores, both first response and stable response occurred faster in COMB than CBT (p < .001), with a probability of sustained early response approximately threefold greater for COMB than CBT. CONCLUSIONS: In the acute treatment of depressed adolescents, FLX and COMB accelerate response relative to PBO, and COMB accelerates response relative to CBT alone. Copyright 2006 copyright American Academy of Child and Adolescent Psychiatry.

Journal of the American Academy of Child & Adolescent Psychiatry, 45(12) : 1412-1418

Weersing, V, Iyengar, S., Kolko, D. J., Birmaher, B., Brent, D. A.

Effectiveness of cognitive-behavioral therapy for adolescent depression: A benchmarking investigation

In this study, we examined the effectiveness of cognitive-behavioral therapy (CBT) for adolescent depression. Outcomes of 80 youth treated with CBT in an outpatient depression specialty clinic, the Services for Teens at Risk Center (STAR), were compared to a \"gold standard\" CBT research benchmark. On average, youths treated with CBT in STAR experienced significantly slower symptom improvement than youths in the CBT benchmark. However, outcomes for STAR teens were more similar to the research benchmark when accounting for differences in referral source (clinical versus advertisement) between the datasets. Results support further efforts to test the effectiveness of CBT in clinically representative community practice settings and samples.

Behavior Therapy, 37(1) : 36-48

Papanikolaou, K., Richardson, C., Pehlivanidis, A., Papadopoulou-Daifoti, Z.

Efficacy of antidepressants in child and adolescent depression: A meta-analytic study

OBJECTIVES: To examine whether antidepressant drugs are superior to placebo in the treatment of juvenile depression. METHOD: Extensive literature search was done to retrieve all randomised controlled and all uncontrolled trials describing children and adolescents with a diagnosis of depression who underwent any antidepressant drug treatment. In order to combine results, separate analyses using random effect models were conducted first for controlled and then for both controlled and open studies. RESULTS: 18 controlled and 23 open trials were submitted to meta- analysis. Tricyclics showed no significant benefit over placebo. Odds ratios for SSRIs were 1.84 (95% CI 1.35-2.50) for controlled and 1.83 (95% CI 1.40-2.40) for controlled and uncontrolled studies suggesting a significant benefit over placebo. Combining all antidepressants also gave confidence interval excluding the value one. CONCLUSIONS: Despite some promising data concerning the use of SSRIs in the treatment of adolescent depression, caution is warranted until the long-term safety of these agents can be demonstrated. Insufficient data are available to judge even the short term merits of these agents in prepubertal children. There is no evidence to support the use of tricyclics in this population.

Journal of Neural Transmission, 113(3) : 399- 415

Nabkasorn, Chanudda, Miyai, Nobuyuki, Sootmongkol, Anek, Junprasert, Suwanna, Yamamoto, Hiroichi, Arita, Mikio, Miyashita, Kazuhisa

Effects of physical exercise on depression, neuroendocrine stress hormones and physiological fitness in adolescent females with depressive symptoms

BACKGROUND: Regular physical exercise may improve a variety of physiological and psychological factors in depressive persons. However, there is little experimental evidence to support this assumption for adolescent populations. We conducted a randomized controlled trial to investigate the effect of physical exercise on depressive state, the excretions of stress hormones and physiological fitness variables in adolescent females with depressive symptoms. METHODS: Forty-nine female volunteers (aged 18-20 years; mean 18.8 +/- 0.7 years) with mild-to-moderate depressive symptoms, as measured by the Centre for Epidemiologic Studies Depression (CES-D) scale, were randomly assigned to either an exercise regimen or usual daily activities for 8 weeks. The subjects were then crossed over to the alternate regimen for an additional 8-week period. The exercise program consisted of five 50-min sessions per week of a group jogging training at a mild intensity. The variables measured were CES-D rating scale, urinary cortisol and epinephrine levels, and cardiorespiratory factors at rest and during exercise endurance test. RESULTS: After the sessions of exercise the CES-D total depressive score showed a significant decrease, whereas no effect was observed after the period of usual daily activities (ANOVA). Twenty-four hour excretions of cortisol and epinephrine in urine were reduced due to the exercise regimen. The training group had a significantly reduced resting heart rate and increased peak oxygen uptake and lung capacity. CONCLUSIONS: The findings of this study suggest that a group jogging exercise may be effective in improving depressive state, hormonal response to stress and physiological fitness of adolescent females with depressive symptoms.

European Journal of Public Health, 16(2) : 179-84

Nemets, Hanah, Nemets, Boris, Apter, Alan, Bracha, Ziva, Belmaker, R.

Omega-3 Treatment of Childhood Depression: A Controlled, Double-Blind Pilot Study

Objective: Major depressive disorder in children may be more common than previously thought, and its therapeutics are unclear. Because of success in a previous study on omega-3 fatty acids in adult major depressive disorder, the authors planned a pilot study of omega-3 fatty acids in childhood major depression. Method: Children who entered the study were between the ages of 6 and 12. Ratings were performed at baseline and at 2, 4, 8, 12, and 16 weeks using Children's Depression Rating Scale (CDRS), Children's Depression Inventory (CDI), and Clinical Global Impression (CGI). Children were randomized to omega-3 fatty acids or placebo as pharmacologic monotherapy. Twenty-eight patients were randomized, and 20 completed at least 1 month's ratings. Results: Analysis of variance showed highly significant effects of omega-3 on symptoms using the CDRS, CDI, and CGI. Conclusions: Omega-3 fatty acids may have therapeutic benefits in childhood depression. (PsycINFO Database Record (c) 2007 APA, all rights reserved) (journal abstract).

American Journal of Psychiatry, 163(6) : 1098-1100