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.     

Residual symptoms after remission of major depressive disorder with fluoxetine and risk of relapse

Background: Many patients with major depressive disorder (MDD) who achieve full remission after antidepressant treatment still have residual depressive symptoms. In this study, we assess the type and frequency of residual symptoms and their relationship to subsequent depressive relapses after remission of major depression with fluoxetine. Method: Five hundred seventy‐six patients with MDD were openly treated with fluoxetine for 12 weeks. Those who responded underwent random assignment, under double‐blind conditions, to continue taking fluoxetine or to switch to placebo for 52 weeks or until relapse. The presence of residual symptoms in patients who achieved remission at the end of the acute phase (N=203) was assessed using the 28‐item Hamilton Depression Rating Scale. Survival analysis was used to examine the effect of residual symptoms on relapse in remitters. Results: More than 90% of patients who met criteria for remission had at least one residual depressive symptom (median=4). The most common were sleep disturbances (insomnia 48.2%, hypersomnia 35.9%) and anxiety (52.7%). The most common individual symptom was middle insomnia (33.5%). No statistically or clinically significant differences in baseline variables were found between remitters with and without residual symptoms. The presence of residual symptoms, the presence of residual insomnia and the global number of residual symptoms did not predict relapse during the continuation phase of the study. Conclusion: The great majority of patients with remission of MDD after treatment with fluoxetine continue to experience selected residual depressive symptoms. The presence of residual symptoms is not significantly associated with an increased risk of relapse. Depression and Anxiety, 2011. © 2010 Wiley‐Liss, Inc.     

Early Prediction of Acute Antidepressant Treatment Response and Remission in Pediatric Major Depressive Disorder

ObjectiveLess than half of youths achieve remission (minimal to no symptoms) after acute antidepressant treatment. Early identification of who will or will not respond to treatment and achieve remission may help clinicians formulate treatment decisions and shorten the time spent on ineffective treatments. In a prospective open-label fluoxetine study, we investigate indicators of acute treatment response and remission.MethodOne hundred sixty-eight children and adolescents, ages 7 to 18 years, with primary diagnoses of major depressive disorder received 12 weeks of fluoxetine treatment. The youths were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia. The outcome measure included the Children's Depression Rating Scale-Revised.ResultsPositive first-degree family history of depression was the only baseline demographic and clinical characteristic that predicted a favorable treatment response (p = .01). The rate of symptom improvement, however, is a good indicator of acute treatment response. A significant symptom reduction (approximately 50%) by week 4 is needed to achieve remission at the end of acute treatment.ConclusionsThis study demonstrated that the rate of symptom improvement during early weeks of acute fluoxetine treatment is a good indicator of remission. Treatment approach may be reevaluated and modified as early as week 4 during acute treatment.     

The Treatment for Adolescents with Depression Study (TADS): methods and message at 12 weeks

Funded by the National Institute of Mental Health, the Treatment for Adolescents With Depression Study (TADS) is intended to evaluate the short-term (12 weeks) and longer-term (36 weeks) effectiveness of four treatments for adolescents with DSM-IV major depressive disorder: clinical management with fluoxetine (FLX), cognitive-behavioral therapy (CBT), FLX and CBT combined (COMB), and clinical management with placebo (PBO). We previously reported that COMB and FLX were more effective in reducing depression than CBT or PBO after 12 weeks of acute treatment. In this special section of the Journal, separate articles extend these findings to the impact of TADS treatments on remission, speed of response, function and quality of life, predictors of outcome, and safety during the first 12 weeks of treatment. To set the stage for the special section, we briefly review the rationale, design, and methods of the TADS; describe the TADS sample to which the TADS findings generalize; using all of the currently available data, summarize the intent-to-treat outcomes across multiple endpoints at 12 weeks; and consider the public health value of the TADS findings in the context of design decisions and methodological limitations of the TADS, including some that may have advantaged the combined treatment condition. Reflecting the ordering of effect sizes at week 12--COMB (0.98) > FLX (0.68) > CBT (-0.03)--combined treatment proved superior to PBO on 15 of 16 endpoints, to CBT on 14 of 16 endpoints, and to FLX on 8 of 16 endpoints, whereas FLX was superior to CBT on 8 of 14 and to PBO on 7 of 16 measures. CBT did not differ from PBO on any measure. Despite the fact that suicidality improved markedly across all of the treatment conditions, suicidal events were twice as common in patients treated with FLX alone than with COMB or CBT alone, perhaps indicating that CBT protects against suicidal events. Thus, combined treatment appears to accelerate recovery relative to CBT and, for some outcomes, FLX alone, while minimizing the risk of suicidality relative to FLX alone. Taking benefit and risk into account, we conclude that the combination of FLX and CBT appears superior to either monotherapy as a treatment for moderate to severe major depressive disorder in adolescents.     

Response versus remission in obsessive-compulsive disorder

OBJECTIVE: To investigate rates of response and remission in adults with obsessive-compulsive disorder (OCD) after 12 weeks of evidence-based treatment. METHOD: Post hoc analyses of response and remission were conducted using data from a multisite, randomized, controlled trial comparing the effects of 12 weeks of exposure and ritual prevention (EX/RP), clomipramine (CMI), their combination (EX/RP+CMI), or pill placebo (PBO) in 122 adults with OCD (DSM-III-R or DSM-IV criteria). Response was defined as a decrease in symptoms; remission was defined as minimal symptoms after treatment. Different response and remission definitions were constructed based on criteria used in prior studies. For each definition, the proportion of responders or remitters in each treatment group was then compared. RESULTS: There were significant differences (p<.05) among the 4 treatment groups in the proportion of responders and remitters. In pairwise comparisons, EX/RP+CMI and EX/RP each produced significantly more responders and remitters than PBO; CMI produced significantly more responders and remitters than PBO for some definitions but not for others. When remission was defined as a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of 12 or less, significantly more EX/RP+CMI (18/31 [58%]) and EX/RP (15/29 [52%]) patients entering treatment achieved remission than either CMI (9/36 [25%]) or PBO (0/26 [0%]) patients. However, even in treatment completers, many CMI and some EX/RP+CMI and EX/RP patients did not achieve remission (remission rates for YBOCS相似文献   

Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability,Safety, Clinical Benefits,and Effect on Cognition

ObjectiveEvidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults.MethodsIn this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition.ResultsCompletion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohen's d = 0.61), and these improvements were sustained in the continuation phase.ConclusionThis pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.     

Changes in weight during a 1-year trial of fluoxetine.

OBJECTIVE: Fluoxetine has been associated with weight loss during acute treatment, but no controlled studies of weight change during long-term treatment with fluoxetine or other selective serotonin reuptake inhibitors have been reported. Weights were assessed for patients whose depressive symptoms had disappeared with acute fluoxetine treatment. Patients were then randomly assigned to continuation treatment with fluoxetine or placebo. METHOD: Patients whose illness had remitted after 12 weeks of treatment with fluoxetine, 20 mg/day, were randomly assigned to receive up to 38 weeks of treatment with fluoxetine or placebo. Weight was assessed at each visit. Change in weight was analyzed during the initial 12 weeks of acute treatment and after 14, 26, and 38 weeks. Relationships between weight change and body mass index and between weight change and appetite change were assessed. RESULTS: During the initial 4 weeks of therapy, a mean absolute weight decrease of 0.4 kg was observed for all patients. Among patients who completed 50 weeks of therapy, the mean absolute weight increase during continuation treatment was similar for both the placebo- and fluoxetine-treated groups. Weight increase was not related to initial body mass index but was related to both poor appetite at study entry and to improvement in appetite after recovery. No patients discontinued therapy because of weight gain. CONCLUSIONS: Acute therapy with fluoxetine is associated with modest weight loss. After remission of depressive symptoms, weight gain for patients taking fluoxetine for longer periods is not different from that for patients taking placebo and is most likely related to recovery from depression.     

Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression

BACKGROUND: The goal was to examine predictors of relapse during continuation/maintenance treatment of major depression that had remitted following 12 to 14 weeks of fluoxetine therapy. METHOD: The study utilizes data collected in a collaborative clinical trial including patients with DSM-III-R major depression at 5 university-affiliated outpatient psychiatry clinics. Three hundred ninety-five patients who remitted with fluoxetine therapy were randomly assigned to 1 of 4 treatments: fluoxetine for 14 weeks followed by placebo for 36 weeks, fluoxetine for 38 weeks followed by placebo for 12 weeks, fluoxetine for 50 weeks, or placebo for 50 weeks. Cox proportional hazard models were used to identify predictors of time to relapse. RESULTS: In addition to the previously reported longitudinal pattern of response during acute treatment, neurovegetative symptom pattern was a predictor of fluoxetine benefit compared with placebo. Greater chronicity predicted poorer survival, which was not differential by treatment. The most robust advantage of fluoxetine was seen for patients with endogenous vegetative symptoms, chronic depression, and acute treatment response characterized by onset in the third week or later and persistence of response once attained. CONCLUSION: Both nonspecific pattern of response and neurovegetative symptoms characteristic of atypical depression were predictive of lack of fluoxetine efficacy in continuation/ maintenance treatment. These findings have importance for both clinical management and analyses of future maintenance trials.     

Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptoms

Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), produces significantly higher remission rates in depressed patients than do the selective serotonin reuptake inhibitors (SSRIs). In this analysis of pooled data, we explored the relationship between differences in treatment efficacy, early improvement of symptoms, and severity of baseline anxiety in depressed patients treated with either venlafaxine or fluoxetine. A pooled analysis was performed on data from 1,454 outpatients with major depression from five double-blind, randomized studies comparing the 6-week efficacy of venlafaxine (542 patients) with fluoxetine (555 patients). The Hamilton rating scale for depression (HAM-D) total and item scores were analyzed at different treatment times up to 6 weeks. Venlafaxine and fluoxetine both produced statistically significant higher response and remission rates compared with placebo starting from week 2 for response and weeks 3 to 4 for remission. Venlafaxine was statistically significantly superior to fluoxetine from week 3 until week 6 in respect of response rate, and from week 2 until week 6 for remission rate. After 1 week of treatment, greater improvement in individual symptoms was observed in the depressed mood, suicide, and psychic anxiety items of the HAM-D scale for both venlafaxine- and fluoxetine-treated patients compared with placebo. Improvement in psychic anxiety was statistically significantly greater with venlafaxine than with fluoxetine. The presence of baseline psychic anxiety correlated significantly to treatment outcome when analyzing the remission rates. In depressed patients with moderate anxiety (HAM-D psychic anxiety score < or = 2), venlafaxine statistically significantly increased remission rates compared with placebo from week 4 until week 6, while a significant effect of fluoxetine on remission rates was observed starting at week 6. Remission rates in the severely anxious depressed patients (score > 2) were statistically significantly higher with venlafaxine than placebo starting from week 3 until the end of the study period, but no difference could be observed between fluoxetine and placebo. Baseline severity of psychic anxiety had a significant impact on remission rates after treatment of patients diagnosed with depression. Venlafaxine's superior remission rates in the more severely anxious patients and its ability to improve psychic anxiety as early as week 1 compared with fluoxetine suggest that venlafaxine's early efficacy on anxiety symptoms may be the basis for its superior efficacy in depression.     

Predictors of fluoxetine remission for hospitalized patients with major depressive disorder

Aim: The goal of treating major depressive disorder is to achieve remission. This prospective study aimed to identify predictors of remission in a cohort of depressive inpatients who received fluoxetine. Methods: A total of 131 newly hospitalized patients with major depressive disorder received a fixed dose of 20 mg/day (the recommended dose from the literature) of fluoxetine for 6 weeks. Symptom severity was assessed using the 17‐item Hamilton Depression Rating Scale at weeks 0, 1, 2, 3, 4 and 6. Remission was defined as a score of ≤7 on the 17‐item Hamilton Depression Rating Scale after 6 weeks of treatment. We compared the remitters and non‐remitters in terms of baseline variables. The Short‐Form‐36 pain interference item was used to assess pain. It was classified as high (score ≥ 3) or low (score < 3). Results: A total of 31 (27.7%) of 112 completers remitted after 6 weeks of treatment. The remitters and non‐remitters did not differ in baseline variables, except pain interference, baseline depression severity, and depression improvement at week 1. Conclusion: These findings obtained from newly hospitalized major depression patients support the previous notion that pain interference, depression severity, and early improvement can be the predictors for remission. Patients with high pain interference, a greater depression severity or a less early improvement are likely to require aggressive treatment early. These data require confirmation and extension to outpatients and other antidepressants.     

Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents

OBJECTIVE: The authors compared fluoxetine and placebo in continuation treatment to prevent relapse of major depressive disorder in children and adolescents. METHOD: 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. RESULTS: 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. CONCLUSIONS: Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression.     

Predictors and moderators of acute outcome in the Treatment for Adolescents with Depression Study (TADS)

OBJECTIVE: To identify predictors and moderators of response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive-behavioral therapy (CBT), both fluoxetine and CBT, or clinical management with pill placebo in the Treatment for Adolescents With Depression Study (TADS). METHOD: Potential baseline predictors and moderators were identified by a literature review. The outcome measure was a week 12 predicted score derived from the Children's Depression Rating Scale-Revised (CDRS-R). For each candidate moderator or predictor, a general linear model was conducted to examine main and interactive effects of treatment and the candidate variable on the CDRS-R predicted scores. RESULTS: Adolescents who were younger, less chronically depressed, higher functioning, and less hopeless with less suicidal ideation, fewer melancholic features or comorbid diagnoses, and greater expectations for improvement were more likely to benefit acutely than their counterparts. Combined treatment, under no condition less effective than monotherapy, was more effective than fluoxetine for mild to moderate depression and for depression with high levels of cognitive distortion, but not for severe depression or depression with low levels of cognitive distortion. Adolescents from high-income families were as likely to benefit from CBT alone as from combined treatment. CONCLUSIONS: Younger and less severely impaired adolescents are likely to respond better to acute treatment than older, more impaired, or multiply comorbid adolescents. Family income level, cognitive distortions, and severity of depression may help clinicians to choose among acute interventions, but combined treatment proved robust in the presence of moderators.     

抑郁症患者焦虑/躯体化症状早期的变化与氟西汀疗效的相关性研究

目的探讨抑郁症患者焦虑／躯体化症状的早期变化对氟西汀抗抑郁治疗达症状缓解的预测作用。方法对103例重症抑郁患者给予氟西汀治疗6w,剂量固定于20 mg／d,于治疗前及治疗后的第1、2、4、6w末用汉密顿抑郁量表17项(HAMD-17)评定临床症状,其中焦虑／躯体化因子分用来评定焦虑／躯体化症状。结果治疗6w末103例患者中32例(31．1％)达到症状缓解标准,71例(68．9 ％)未达到症状缓解标准。早期HAMD-17中焦虑／躯体化因子分及胃肠道症状条目分的变化与症状缓解存在正相关,而该因子中其余条目的变化与症状缓解不相关。结论HAMD-17中焦虑／躯体化因子分及胃肠道症状有关的条目分早期改善可能是氟西汀治疗后症状能基本缓解的预测因子。     

Research knowledge among the participants in the Treatment for Adolescents With Depression Study (TADS)

OBJECTIVE: We examined the extent to which parents and adolescents participating in the Treatment for Adolescents With Depression Study (TADS) understood key aspects of the study. METHOD: TADS was a clinical trial comparing the effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), their combination, and placebo in 439 adolescents (12-17 years old) with major depressive disorder. Six weeks after starting treatment, adolescents and their parents were asked to complete a questionnaire about critical elements of the trial. RESULTS: Completion rate was 67.2% for adolescents (N = 295) and 73.6% for parents (N = 323). More than 90% of the completers knew of the main purpose of the trial, possible assignment to placebo, and their right to withdraw participation at any time. However, about one third overall (and 49% in the CBT group) described TADS as "education" rather than "research." Of 12 questions, the mean number of correct answers was 10.3 (SD 1.7) among adolescents and 11.2 (SD 1.2) among parents (p <.0001). The most frequently stated reason for TADS participation was the pursuit of high-quality care. CONCLUSIONS: Most parents and adolescents were well-informed research participants. Difficulties in appreciating the research nature of the trial, however, emerged, especially among participants assigned to psychotherapy. Parents were overall better informed than adolescents.     

Relative Cost-Effectiveness of Treatments for Adolescent Depression: 36-Week Results From the TADS Randomized Trial

ObjectiveThe cost-effectiveness of three active interventions for major depression in adolescents was compared after 36 weeks of treatment in the Treatment of Adolescents with Depression Study.MethodOutpatients aged 12 to 18 years with a primary diagnosis of major depression participated in a randomized controlled trial conducted at 13 U.S. academic and community clinics from 2000 to 2004. Three hundred twenty-seven participants randomized to 1 of 3 active treatment arms, fluoxetine alone (n = 109), cognitive-behavioral therapy (n = 111) alone, or their combination (n = 107), were evaluated for a 3-month acute treatment and a 6-month continuation/maintenance treatment period. Costs of services received for the 36 weeks were estimated and examined in relation to the number of depression-free days and quality-adjusted life-years. Cost-effectiveness acceptability curves were also generated. Sensitivity analyses were conducted to assess treatment differences on the quality-adjusted life-years and cost-effectiveness measures.ResultsCognitive-behavioral therapy was the most costly treatment component (mean $1,787 [in monotherapy] and $1,833 [in combination therapy], median $1,923 [for both]). Reflecting higher direct and indirect costs associated with psychiatric hospital use, the costs of services received outside Treatment of Adolescents with Depression Study in fluoxetine-treated patients (mean $5,382, median $2,341) were significantly higher than those in participants treated with cognitive-behavioral therapy (mean $3,102, median $1,373) or combination (mean $2,705, median $927). Accordingly, cost-effectiveness acceptability curves indicate that combination treatment is highly likely (>90%) to be more cost-effective than fluoxetine alone at 36 weeks. Cognitive-behavioral therapy is not likely to be more cost-effective than fluoxetine.ConclusionsThese findings support the use of combination treatment in adolescents with depression over monotherapy. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(7):711–720     

The Treatment for Adolescents With Depression Study (TADS): long-term effectiveness and safety outcomes

CONTEXT: The Treatment for Adolescents With Depression Study evaluates the effectiveness of fluoxetine hydrochloride therapy, cognitive behavior therapy (CBT), and their combination in adolescents with major depressive disorder. OBJECTIVE: To report effectiveness outcomes across 36 weeks of randomized treatment. DESIGN AND SETTING: Randomized, controlled trial conducted in 13 academic and community sites in the United States. Cognitive behavior and combination therapies were not masked, whereas administration of placebo and fluoxetine was double-blind through 12 weeks, after which treatments were unblinded. Patients assigned to placebo were treated openly after week 12, and the placebo group is not included in these analyses by design. PARTICIPANTS: Three hundred twenty-seven patients aged 12 to 17 years with a primary DSM-IV diagnosis of major depressive disorder. INTERVENTIONS: All treatments were administered per protocol. MAIN OUTCOME MEASURES: The primary dependent measures rated blind to treatment status by an independent evaluator were the Children's Depression Rating Scale-Revised total score and the response rate, defined as a Clinical Global Impressions-Improvement score of much or very much improved. RESULTS: Intention-to-treat analyses on the Children's Depression Rating Scale-Revised identified a significant time x treatment interaction (P < .001). Rates of response were 73% for combination therapy, 62% for fluoxetine therapy, and 48% for CBT at week 12; 85% for combination therapy, 69% for fluoxetine therapy, and 65% for CBT at week 18; and 86% for combination therapy, 81% for fluoxetine therapy, and 81% for CBT at week 36. Suicidal ideation decreased with treatment, but less so with fluoxetine therapy than with combination therapy or CBT. Suicidal events were more common in patients receiving fluoxetine therapy (14.7%) than combination therapy (8.4%) or CBT (6.3%). CONCLUSIONS: In adolescents with moderate to severe depression, treatment with fluoxetine alone or in combination with CBT accelerates the response. Adding CBT to medication enhances the safety of medication. Taking benefits and harms into account, combined treatment appears superior to either monotherapy as a treatment for major depression in adolescents.     

When should a trial of fluoxetine for major depression be declared failed?

OBJECTIVE: Although the newer antidepressants are widely used, little is known about how long it takes to see their full effect. The authors sought to determine how many weeks a fluoxetine trial with no improvement should continue before treatment is changed. METHOD: The data involved 840 patients in a 12-week open trial of fluoxetine, 20 mg/day, followed by a blinded, placebo-controlled discontinuation study. Outcomes at 4, 6, 8, 10, and 12 weeks were classified as nonresponse, partial response, response, and remission and were based on Hamilton Depression Rating Scale scores. The rate of remission at week 12 was calculated for each group of patients without remission at the earlier time points. The time to relapse during weeks 13-26 of the discontinuation study was examined in patients taking placebo and fluoxetine in relation to status at week 6. RESULTS: Patients unimproved at week 6 had a remission rate at week 12 of 31%-41%. For patients with remission at week 12, level of improvement at week 6 did not affect prognosis in weeks 13-26. Of the unimproved patients at week 8, 23% had remissions by week 12. The week 12 remission rate for unimproved patients at week 4 was clearly high enough to justify continued treatment; the rate for unimproved patients at week 10 was too low. CONCLUSIONS: These data suggest that nonresponse to fluoxetine should not be declared until 8 weeks of treatment have elapsed. Practitioners should discuss trial length with patients at the beginning of treatment.     

Moclobemide and fluoxetine in the prevention of relapses following acute treatment of depression

The efficacy of moclobemide (378 mg ± 76 mg/day) and fluoxetine (36 mg ± 8 mg/day) in preventing relapse was studied during 12 weeks of continuation treatment after a 6-week initial trial. Fifty-nine patients with Hamilton Depression Rating Scale (HDRS) scores of 16 or less were enrolled; 29 continued to receive moclobemide and 30 fluoxetine. Efficacy was measured using a 17-item HDRS, the Montgomery-Åsberg Depression Rating Scale and the Clinical Global Impression. Improvement in quality of life was measured using a Medical Outcome Study Short-form General Health Survey and the 15D Measure of Quality of Life. Twenty-three per cent of the patients in the fluoxetine group dropped out of the study and 10% in the moclobemide group. Two patients (7%) in the moclobemide group and one (3%) in the fluoxetine group suffered a relapse. Health status and quality of life improved in both drug groups during a 12-week continuation period. The reports of adverse events fell to one third during the continuation phase. The results indicate that benefits may be gained from extending acute treatment.     

Depressive Symptoms and Clinical Status During the Treatment of Adolescent Suicide Attempters (TASA) Study

ObjectiveTo examine the course of depression during the treatment of adolescents with depression who had recently attempted suicide.MethodAdolescents (N = 124), ages 12 to 18 years, with a 90-day history of suicide attempt, a current diagnosis of depressive disorder (96.0% had major depressive disorder), and a Children's Depression Rating Scale-Revised (CDRS-R) score of 36 or higher, entered a 6-month treatment with antidepressant medication, cognitive-behavioral therapy focused on suicide prevention, or their combination (Comb), at five academic sites. Treatment assignment could be either random or chosen by study participants. Intent-to-treat, mixed effects regression models of depression and other relevant ratings were estimated. Improvement and remission rates were computed with the last observation carried forward.ResultsMost patients (n = 104 or 84%) chose treatment assignment, and overall, three fourths (n = 93) received Comb. In Comb, CDRS-R declined from a baseline adjusted mean of 49.6 (SD 12.3) to 38.3 (8.0) at week 12 and to 27.0 (10.1) at week 24 (p < .0001), with a Clinical Global Impression -defined improvement rate of 58.0% at week 12 and 72.2% at week 24 and a remission (CDRS-R ≤28) rate of 32.5% at week 12 and 50.0% at week 24. The CDRS-R and the Scale for Suicidal Ideation scores were correlated at baseline (r= 0.43, p < .0001) and declined in parallel.ConclusionsWhen vigorously treated with a combination of medication and psychotherapy, adolescents with depression who have recently attempted suicide show rates of improvement and remission of depression that seem comparable to those observed in nonsuicidal adolescents with depression.     

Type of residual symptom and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine

Relapse of major depressive disorder (MDD) is a common clinical problem. Identifying relapse predictors could lead to strategies that reduce relapse risk. This study is designed to determine whether residual symptoms predict relapse risk during the continuation/maintenance treatment of MDD. 570 MDD patients received open-label fluoxetine for 12 weeks. Under double blind conditions, 262 patients who responded by week 12 were randomly assigned to continue fluoxetine or switch to placebo for 52 weeks or until relapse. Residual symptoms were measured using the Symptom Checklist-90 and the Symptom Questionnaire. The relationship between residual symptom severity and relapse risk was assessed. Without adjusting for overall residual symptom severity, a greater severity of residual obsessive-compulsive and phobic anxiety symptoms predicted greater relapse risk. After adjusting for overall residual symptom severity, only severity of phobic anxiety symptoms predicted relapse risk. The predictive value of phobic anxiety symptoms with respect to relapse risk was independent of treatment assignment. The results indicated that there may be a specific pattern of residual symptoms associated with depressive relapse during antidepressant continuation/maintenance, which is unrelated to treatment assignment. Future studies are needed to further explore the relationship between residual symptoms and relapse risk in MDD. Clinical implications: (1) It is important to treat residual symptoms among antidepressant responders/remitters in order to decrease relapse risk. (2) Clinicians should target residual phobic anxiety symptoms in order to decrease relapse risk. (3) Clinicians should target residual obsessive-compulsive symptoms in order to decrease relapse risk. Limitations: (1) limited generalizability due to inclusion/exclusion criteria; (2) lack of active comparator treatment group; (3) post hoc analysis.