Treatment of Resistant Depression in Adolescents (TORDIA): week 24 outcomes. Achievement and maintenance of sustained response during the Treatment for Adolescents With Depression Study continuation and maintenance therapy. Fluoxetine in child and adolescent depression: acute and maintenance treatment. Cognitive-behavioral treatment of adolescent depression: efficacy of acute group treatment and booster sessions. Rapid response to psychosocial treatment for adolescent depression: a two-year follow-up. Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents. Cognitive-behavioral therapy to prevent relapse in pediatric responders to pharmacotherapy for major depressive disorder. Fluoxetine treatment for prevention of relapse of depression in children and adolescents: a double-blind, placebo-controlled study.
The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial after 24 weeks of treatment, including remission and relapse rates and predictors of treatment outcome.
                Adolescents (ages 12-18 years) with selective serotonin reuptake inhibitor (SSRI)-resistant depression were randomly assigned to either a medication switch alone (alternate SSRI or venlafaxine) or a medication switch plus cognitive-behavioral therapy (CBT). At week 12, responders could continue in their assigned treatment arm and nonresponders received open treatment (medication and/or CBT) for 12 more weeks (24 weeks total). The primary outcomes were remission and relapse, defined by the Adolescent Longitudinal Interval Follow-Up Evaluation as rated by an independent evaluator.
                Of 334 adolescents enrolled in the study, 38.9% achieved remission by 24 weeks, and initial treatment assignment did not affect rates of remission. Likelihood of remission was much higher (61.6% versus 18.3%) and time to remission was much faster among those who had already demonstrated clinical response by week 12. Remission was also higher among those with lower baseline depression, hopelessness, and self-reported anxiety. At week 12, lower depression, hopelessness, anxiety, suicidal ideation, family conflict, and absence of comorbid dysthymia, anxiety, and drug/alcohol use and impairment also predicted remission. Of those who responded by week 12, 19.6% had a relapse of depression by week 24.
                Continued treatment for depression among treatment-resistant adolescents results in remission in approximately one-third of patients, similar to adults. Eventual remission is evident within the first 6 weeks in many, suggesting that earlier intervention among nonresponders could be important. The Treatment for Adolescents With Depression Study evaluated fluoxetine (FLX), cognitive behavioral therapy (CBT), and FLX/CBT combination (COMB) vs pill placebo in 439 adolescents with major depressive disorder. Treatment consisted of 3 stages: (1) acute (12 weeks), (2) continuation (6 weeks), and (3) maintenance (18 weeks).
                To examine rates of achieving and maintaining sustained response during continuation and maintenance treatments.
                Randomized controlled trial. Response was determined by blinded independent evaluators.
                Thirteen US sites.
                Two hundred forty-two FLX, CBT, and COMB patients in their assigned treatment at the end of stage 1.
                Stage 2 treatment varied based on stage 1 response. Stage 3 consisted of 3 CBT and/or pharmacotherapy sessions and, if applicable, continued medication.
                Sustained response was defined as 2 consecutive Clinical Global Impression-Improvement ratings of 1 or 2 ("full response"). Patients achieving sustained response were classified on subsequent nonresponse status.
                Among 95 patients (39.3%) who had not achieved sustained response by week 12 (29.1% COMB, 32.5% FLX, and 57.9% CBT), sustained response rates during stages 2 and 3 were 80.0% COMB, 61.5% FLX, and 77.3% CBT (difference not significant). Among the remaining 147 patients (60.7%) who achieved sustained response by week 12, CBT patients were more likely than FLX patients to maintain sustained response through week 36 (96.9% vs 74.1%; P = .007; 88.5% of COMB patients maintained sustained response through week 36). Total rates of sustained response by week 36 were 88.4% COMB, 82.5% FLX, and 75.0% CBT.
                Most adolescents with depression who had not achieved sustained response during acute treatment did achieve that level of improvement during continuation and maintenance therapies. The possibility that CBT may help the subset of adolescents with depression who achieve early sustained response maintain their response warrants further investigation.
                clinicaltrials.gov Identifier: NCT00006286. The objective was to present naturalistic 1-year follow-up information of 96 child and adolescent outpatients with major depressive disorder who had been randomized in an 8-week double-blind, placebo-controlled trial of fluoxetine. Subjects were children and adolescents, ages 8-18 years, who were entered in a randomized clinical trial of fluoxetine. Following the acute treatment trial, treatment was not controlled. At 6 months and 1 year, the subjects and parents were interviewed using the Kiddie Longitudinal Interval Follow-up Evaluation (K-LIFE) for course of depression. Eighty-seven of the 96 subjects were followed for 1 year. Of these, 74 (85%) recovered from the depressive episode during that time (47 on fluoxetine, 22 on no medication, and 5 on other antidepressants or lithium). Twenty-nine of the subjects (39%) who recovered had a recurrence of depression during the 1-year follow-up, with 55% of these occurring within 6 months. Results of this study are similar to adult studies, with respect to response and recovery of depressive episodes. Most patients (85%) recover from the episode within 1 year, but approximately 40% have a recurrence within 12 months, which is a higher recurrence rate than in adults. Recovery was associated with younger age, lower severity of depressive symptoms, higher family functioning, and fewer comorbid diagnoses. Recurrence, which occurs both on and off medication, was difficult to predict, as there was little clinical data associated with recurrence in this population. This trial examined the effects of both acute and maintenance cognitive-behavioral therapy (CBT) for depressed adolescents.
                Adolescents with major depression or dysthymia (N = 123) were randomly assigned to 1 of 3 eight-week acute conditions: adolescent group CBT (16 two-hour sessions); adolescent group CBT with a separate parent group; or waitlist control. Subsequently, participants completing the acute CBT groups were randomly reassigned to 1 of 3 conditions for the 24-month follow-up period: assessments every 4 months with booster sessions; assessments only every 4 months; or assessments only every 12 months.
                Acute CBT groups yielded higher depression recovery rates (66.7%) than the waitlist (48.1%), and greater reduction in self-reported depression. Outcomes for the adolescent-only and adolescent + parent conditions were not significantly different. Rates of recurrence during the 2-year follow-up were lower than found with treated adult depression. The booster sessions did not reduce the rate of recurrence in the follow-up period but appeared to accelerate recovery among participants who were still depressed at the end of the acute phase.
                The findings, which replicate and expand upon a previous study, support the growing evidence that CBT is an effective intervention for adolescent depression. To examine the differential course and treatment outcome of patients who participated in a randomized clinical trial, comparing cognitive, family, and supportive psychotherapies for adolescent major depressive disorder.
                In a sample of 100 depressed adolescents, remission, clinical recovery, recurrence, and functional improvement were examined at the end of acute treatment and at 1- and 2-year follow-up, according to their type of response to treatment. Rapid response was defined as a decline of > or = 50% in the Beck Depression Inventory (BDI) score from pretreatment until the beginning of the second session of psychotherapy, intermediate as a decline of < 50% but > 0%, and initial nonresponse as a BDI score that stayed the same or increased.
                Rapid responders showed a better outcome at acute treatment, 1-year, and in some measures, 2-year follow-up. For those who had recurrences over time, rapid responders showed a longer period before recurrence. Subjects were most likely to respond rapidly, or not at all, in the supportive cell.
                These findings suggest that milder forms of depression may benefit from initial supportive therapy or short trials of more specialized types of psychotherapy. The use of a placebo run-in period might help to "wash out" nonspecific responders. The authors compared fluoxetine and placebo in continuation treatment to prevent relapse of major depressive disorder in children and adolescents.
                After a detailed evaluation, children and adolescents 7-18 years of age with major depressive disorder were treated openly with fluoxetine. Those who had an adequate response after 12 weeks, as indicated by a Clinical Global Impression improvement score of 1 or 2 and a decrease of at least 50% in Children's Depression Rating Scale-Revised score, were randomly assigned to receive fluoxetine or placebo for an additional 6 months. The primary outcome measures were relapse and time to relapse. Relapse was defined as either a score of 40 or higher on the Children's Depression Rating Scale with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. Additional analyses were conducted with relapse defined only as a score of 40 or higher on the Children's Depression Rating Scale.
                Of 168 participants enrolled in acute fluoxetine treatment, 102 were randomly assigned to continuation treatment with fluoxetine (N=50) or placebo (N=52). Of these, 21 participants (42.0%) in the fluoxetine group relapsed, compared with 36 (69.2%) in the placebo group, a significant difference. Similarly, under the stricter definition of relapse, fewer participants in the fluoxetine group relapsed (N=11; 22.0%) than in the placebo group (N=25; 48.1%). Time to relapse was significantly shorter in the placebo group.
                Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression. We present results of a feasibility test of a sequential treatment strategy using continuation phase cognitive-behavioral therapy (CBT) to prevent relapse in youths with major depressive disorder (MDD) who have responded to acute phase pharmacotherapy.
                Forty-six youths (ages 11-18 years) who had responded to 12 weeks of treatment with fluoxetine were randomized to receive either 6 months of continued antidepressant medication management (MM) or antidepressant MM plus relapse prevention CBT (MM+CBT). Primary outcome was time to relapse, defined as a Childhood Depression Rating Scale-Revised score of 40 or higher and 2 weeks of symptom worsening or clinical deterioration warranting alteration of treatment to prevent full relapse.
                Cox proportional hazards regression, adjusting for depression severity at randomization and for the hazard of relapsing by age across the trial, revealed that participants in the MM treatment group had a significantly greater risk for relapse than those in the MM+CBT treatment group (hazard ratio = 8.80; 95% confidence interval 1.01-76.89; chi = 3.86, p =.049) during 6 months of continuation treatment. In addition, patient satisfaction was significantly higher in the MM+CBT group. No differences were found between the two treatment groups on attrition rate, serious adverse events, and overall global functioning.
                These preliminary results suggest that continuation phase CBT reduces the risk for relapse by eightfold compared with pharmacotherapy responders who received antidepressant medication alone during the 6-month continuation phase. To compare fluoxetine 20 to 60 mg/day with placebo for prevention of relapse of major depressive disorder in children and adolescents who had achieved Children's Depression Rating Scale, Revised scores of < or =28 during treatment with fluoxetine 20 to 60 mg.
                In this 32-week relapse-prevention phase of a double-blind, multicenter, placebo-controlled 51-week study, 20 patients continued to receive their fixed dose of fluoxetine (F/F group), while 20 similar patients were switched to placebo (F/P group). Definition of relapse for the primary analysis was a Children's Depression Rating Scale, Revised score of >40 with a 2-week history of clinical deterioration or relapse in the opinion of the physician. Adverse events were compared between treatment groups to assess discontinuation-emergent adverse events.
                Mean time to relapse was longer in the F/F recipients than in the F/P recipients (p=.046). Relapse occurred in an estimated 34% in the F/F cohort and 60% in the F/P cohort. Incidence of adverse events and tolerability were similar in the F/F and F/P groups, suggesting that fluoxetine is not associated with significant discontinuation events.
                Fluoxetine 20 to 60 mg/day was well tolerated and can significantly delay relapse of major depressive disorder symptoms in children and adolescents.
Currently, there is little evidence to conclude which type of treatment approach is most effective in preventing relapse or recurrence of depressive episodes in children and adolescents. Limited trials found that antidepressant medication reduces the chance of relapse-recurrence in the future, however, there is considerable diversity in the design of trials, making it difficult to compare outcomes across studies. Some of the research involving psychological therapies is encouraging, however at present more trials with larger sample sizes need to be conducted in order to explore this treatment approach further.