Differential effects of nefazodone and cognitive behavioral analysis system of psychotherapy on insomnia associated with chronic forms of major depression

BACKGROUND: The antidepressant nefazodone and the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) were recently found to have significant, additive effects in a large multicenter study of chronic forms of major depression. As nefazodone-mediated blockade of serotonin-2 receptors may directly relieve insomnia associated with depression, we examined the more specific effects of CBASP and nefazodone, singly and in combination, on sleep disturbances. METHOD: A total of 597 chronically depressed outpatients (DSM-III-R criteria) with at least 1 insomnia symptom were randomly assigned to 12 weeks of treatment with nefazodone (mean final dose = 466 mg/day), CBASP (mean = 16.0 sessions), or the combination (mean dose = 460 mg/day plus a mean of 16.2 CBASP sessions). Continuous and categorical insomnia outcomes, derived from standard clinician- and self-rated assessments, were compared. RESULTS: Patients receiving nefazodone (either alone or in combination with CBASP) obtained significantly more rapid and greater ultimate improvement in insomnia ratings when compared with those treated with CBASP alone. This difference was maximal by the fourth week of therapy and sustained thereafter. Combined treatment did not result in markedly better insomnia scores than treatment with nefazodone alone on most measures, although patients receiving both CBASP and nefazodone were significantly more likely (p < .001) to achieve > or = 50% decrease in insomnia severity. CONCLUSION: Despite comparable antidepressant efficacy, monotherapy with nefazodone or CBASP resulted in markedly different effects on the magnitude and temporal course of insomnia symptoms associated with chronic forms of major depression. Patients receiving the combination of psychotherapy and pharmacotherapy benefited from both the larger and more rapid improvements in insomnia associated with nefazodone therapy and the later-emerging effects of CBASP on the overall depressive syndrome.     

Sexual function and satisfaction in the treatment of chronic major depression with nefazodone,psychotherapy, and their combination

BACKGROUND: Changes in sexual interest/satisfaction and function are frequently associated with major depression and the use of some antidepressant treatments. This study compares the effects of antidepressant medication, psychotherapy, and combined treatment on sexual interest/satisfaction and function in patients with chronic major depression. METHOD: Outpatients with chronic forms of DSM-IV major depressive disorder (N = 681) were randomly assigned to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined nefazodone/CBASP. The Modified Rush Sexual Inventory was used to assess sexual functioning, and the 24-item Hamilton Rating Scale for Depression was used to assess depressive symptoms. RESULTS: At baseline, 65% of men and 48% of women reported some sexual dysfunction. Statistically significant linear improvement in sexual interest/satisfaction was noted across all 3 treatment groups (p < .001). Additionally, significant improvement in sexual function was observed across all 3 treatment groups on a composite measure of female sexual function (p < .001). Controlling for depressive symptoms and gender, combined treatment produced greater improvement in total sexual interest/satisfaction than CBASP alone (p = .007), but was not significantly different from nefazodone alone. Improvement in depressive symptoms was associated with improved sexual interest/satisfaction for men and women and, for men, improved sexual functioning. CONCLUSION: Chronic depression is associated with high rates of sexual dysfunction. Treatment with nefazodone, CBASP, and combined treatment improved sexual interest/satisfaction, with greatest improvement observed with combined treatment.     

Review of Treating chronic depression with disciplined personal involvement: Cognitive behavioral analysis system of psychotherapy (CBASP)

Reviews the book, Treating chronic depression with disciplined personal involvement: Cognitive behavioral analysis system of psychotherapy (CBASP) by James P. McCullough Jr. (see record 2006-11486-000). The premise of this book is that therapeutic neutrality does not apply to the psychotherapy of chronically depressed individuals, and that disciplined personal involvement is an efficacious and perhaps necessary component of their treatment. Cognitive behavioral analysis system of psychotherapy (CBASP) is a learning model, in which the therapist focuses on teaching patients to recognize the consequences of their behavior. McCullough addresses practical and theoretical objections to this therapeutic approach, which include fears of overinvolvement, and inappropriate behavior, and clinical risks of flooding patients with excessively personal information and content. Ultimately, most readers will finish reading this volume with many open questions, some specific to McCullough's approach, others related to the challenging condition of chronic depression itself. (PsycINFO Database Record (c) 2010 APA, all rights reserved).     

Incidence and predictors of relapse during continuation treatment of major depression with SSRI, interpersonal psychotherapy, or their combination

Background: Despite the availability of many effective treatments, patients with major depression remain at risk for relapse following remission of a depressive episode. The aims of this report are to estimate the relapse rates associated with the acute treatment strategies employed in this study and to investigate demographic and clinical predictors of relapse. Methods: The study sample includes 225 patients who entered the 6‐month continuation treatment phase after remitting from an acute depressive episode. Treatment during the acute phase was interpersonal psychotherapy, SSRI (escitalopram), or the combination of the two when monotherapy did not lead to response. Relapse was defined by a Hamilton Depression Rating Scale score ≥15, confirmed by the diagnosis of major depression. The probability of relapsing was modeled using logistic regression. Three separate models were fit with subgroups of covariates. Results: Of the 225 patients, 29 (12.9%) relapsed and 28 (12.4%) discontinued the protocol prematurely. The proportion of patients who relapsed among the group requiring combination treatment to achieve remission was three times as high as among patients who had remitted with monotherapy. In the final logistic regression model, older age, higher baseline HDRS scores, last month (residual) depressive mood spectrum factor score, and requiring combination treatment to achieve remission were each associated with an increased likelihood of relapse. Conclusions: Our results suggest that greater initial depression severity, greater difficulty in stabilizing symptoms, and presence of residual mood spectrum symptoms once remission is achieved are predictive of relapse. Risk of relapse is more likely as age increases, partly because aging confers lower resilience. Depression and Anxiety, 2011. © 2011 Wiley Periodicals, Inc.     

Does psychosocial functioning improve independent of depressive symptoms? A comparison of nefazodone, psychotherapy, and their combination.

BACKGROUND: Although it is known that antidepressant treatment improves psychosocial functioning, whether such changes occur independent of depressive symptoms is not known. This study compared efficacy of nefazodone, psychotherapy, and their combination in improving psychosocial functioning in chronically depressed outpatients. METHODS: Patients with chronic forms of major depressive disorder were randomized to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined nefazodone/CBASP. Psychosocial assessments measured overall psychosocial functioning, work functioning, interpersonal functioning, and general health. RESULTS: Relative to community norms, patients with chronic major depression evidenced substantially impaired psychosocial functioning at baseline. Combined treatment produced significantly greater psychosocial improvement than either CBASP alone or nefazodone alone on all primary measures. Combined treatment remained superior to nefazodone on primary measures of work, social, and overall functioning, and superior to CBASP on social functioning when depressive symptoms were controlled. Unlike the two groups receiving nefazodone, CBASP alone's effect on psychosocial function was relatively independent of symptom change. Psychosocial functioning improved more slowly than depressive symptoms, and moderate psychosocial impairments remained at end point. CONCLUSIONS: Combined treatment had greater effect than either monotherapy. Change in depressive symptoms did not fully explain psychosocial improvement. Moderate residual psychosocial impairment remained, suggesting the need for continuation/maintenance treatment.     

Short psychodynamic supportive psychotherapy, antidepressants, and their combination in the treatment of major depression: a mega-analysis based on three randomized clinical trials

The efficacy of Short Psychodynamic Supportive Psychotherapy (SPSP) has not yet been compared with pharmacotherapy. A mega-analysis based on three original Randomized Clinical Trials (RCTs) was performed. Patients with (mild to moderate) major depressive disorder were randomized in (24 weeks) SPSP (n = 97), pharmacotherapy (n = 45), or their combination (n = 171). Efficacy was assessed by the Hamilton Depression Rating Scale (HDRS), Clinical Global Impression of Severity and of Improvement (CGI-S), the Symptom Checklist (SCL; depression subscale) and the Quality of Life Depression Scale (QLDS). Pearson chi(2) calculations were used to compare success rates. Analyses of covariance (ANCOVAs) were used to test inter-group differences. Success rates indicated that independent observers (HDRS) found no differences in symptom reduction between SPSP and pharmacotherapy (P = 0.214), but therapists (CGI-S, P = 0.026), and patients (SCL, P = 0.036) favored SPSP. Combined therapy was found superior to pharmacotherapy by all three (patients (P = 0.000), therapists (P = 0.024), independent observers (P = 0.024)). Independent observers (P = 0.062) and therapists (P = 0.430) found no differences between combined therapy and SPSP, but patients (P = 0.016) found combined therapy to be superior. As far as quality of life is concerned, success rates indicated that patients (QLDS) found no differences between SPSP and pharmacotherapy (P = 0.073) or between SPSP and combined therapy (P = 0.217). However, they found combined therapy superior to pharmacotherapy (P = 0.015). The results of the mega-analysis suggest that combined therapy is more efficacious than pharmacotherapy. SPSP and pharmacotherapy seem equally efficacious, except for some indications that patients and therapists favor SPSP for symptom reduction. Combined therapy and SPSP also seem equally efficacious, except that patients think that the first is better in symptom reduction.     

Open trial of nefazodone among Hispanics with major depression: efficacy, tolerability, and adherence issues

The efficacy and tolerability of nefazodone in the treatment of major depression among Spanish-monolingual Hispanics was examined and compared to historical controls among English-speaking, predominantly non-Hispanic subjects. Fifty monolingual Hispanic outpatients with major depression and a HAM-D17 score > or = 18 were treated with nefazodone in a flexible-dose 8-week open-label protocol. Sixty-three percent of the intent-to-treat (ITT) sample with > or = 1 efficacy visit were considered responders according to CGI-I criteria, falling within the range of response rates (58-69%) reported in six prior nefazodone trials with non-Hispanic subjects. Significant improvement was found for the ITT and completer samples in HAM-D17, HAM-D28, and SCL-90 scores and in two measures of psychosocial functioning. Endpoint mean dose in the ITT sample was 379 mg/day (SD = 170), also within the range of previous trials (321-472 mg/day). Adverse effects were not elevated, with only dry mouth (8%) reported by > 6% of subjects. However, 42% of the sample dropped out of treatment before study termination, usually because of side effects or due to family or work difficulties, a higher rate than previously reported for nefazodone (21-33%). This open trial finds nefazodone to be an efficacious treatment for major depression among monolingual Hispanics, with comparable efficacy to previous controlled trials among non-Hispanic subjects. Double-blind studies are required to confirm this comparable efficacy. Mean endpoint doses and adverse effect rates similar to previous trials do not support the need for reduced doses of nefazodone among Hispanics. However, an elevated rate of treatment discontinuation threatens treatment efficacy among this population. Causes for this elevated rate require explanation, given the apparently unremarkable pattern of adverse effect reports.     

Distinctive and common neural underpinnings of major depression,social anxiety,and their comorbidity

Assessing neural commonalities and differences among depression, anxiety and their comorbidity is critical in developing a more integrative clinical neuroscience and in evaluating currently debated categorical vs dimensional approaches to psychiatric classification. Therefore, in this study, we sought to identify patterns of anomalous neural responding to criticism and praise that are specific to and common among major depressive disorder (MDD), social anxiety disorder (SAD) and comorbid MDD-SAD. Adult females who met formal diagnostic criteria for MDD, SAD or MDD-SAD and psychiatrically healthy participants underwent functional magnetic resonance imaging as they listened to statements directing praise or criticism at them or at another person. MDD groups showed reduced responding to praise across a distributed cortical network, an effect potentially mediated by thalamic nuclei undergirding arousal-mediated attention. SAD groups showed heightened anterior insula and decreased default-mode network response to criticism. The MDD-SAD group uniquely showed reduced responding to praise in the dorsal anterior cingulate cortex. Finally, all groups with psychopathology showed heightened response to criticism in a region of the superior frontal gyrus implicated in attentional gating. The present results suggest novel neural models of anhedonia in MDD, vigilance-withdrawal behaviors in SAD, and poorer outcome in MDD-SAD. Importantly, in identifying unique and common neural substrates of MDD and SAD, these results support a formulation in which common neural components represent general risk factors for psychopathology that, due to factors that are present at illness onset, lead to distinct forms of psychopathology with unique neural signatures.     

Comparative efficacy of cognitive behavioral therapy,fluoxetine, and their combination in depressed adolescents: Initial lessons from the treatment for adolescents with depression study

Adolescents with major depressive disorder (MDD), their families and clinicians experience significant challenges when weighing the potential risks versus benefits of available choices in the treatment of MDD. Although MDD is highly prevalent in adolescents and is associated with marked suffering, impairment and risk of suicide, the scientific data regarding the safety and efficacy of treatments for pediatric depression are limited. Controlled clinical trials have provided support for the use of psychotherapy and fluoxetine for the treatment of pediatric depression, but until recently no information on the comparative efficacy of these recommended interventions alone or in combination was available. The Treatment for Adolescents with Depression Study provides a very important therapeutic advance in the field by convincingly showing that combination treatment with cognitive behavioral therapy and fluoxetine has the best benefit to risk ratio for adolescents with moderate to severe depression, and is superior to monotherapy. Moreover, the study results confirm that fluoxetine alone is effective in the treatment of depressed adolescents.     

The efficacy of long-term psychodynamic psychotherapy,fluoxetine and their combination in the outpatient treatment of depression

Abstract

Objective: There are few randomized controlled trials examining the efficacy of long-term psychodynamic psychotherapy (LTPP) in depression treatment. LTPP was compared with fluoxetine treatment and their combination; Methods: 272 depressed patients (aged 26–34, 72% with a first episode of depression) were randomized to receive LTPP (one session/week), fluoxetine treatment (20–60 mg/day) or their combination for 24 months. Beck Depression Inventory (BDI) was the outcome measure. The psychotherapy was not manualized and the treatment took place under real-life conditions in an outpatient psychiatric clinic. Results: Intention-to-treat analyses indicated that all the treatments were associated with significant reductions in the BDI scores (mean reduction of 18.88 BDI points). Furthermore, LTPP and combination therapy were more effective in reducing BDI scores than fluoxetine alone (22.08 and 22.04 vs. 12.53 BDI points). Conclusions: LTPP, pharmacological treatment with fluoxetine and their combination are effective in reducing symptoms of patients with moderate depression. LTPP and combined treatment were more effective compared to fluoxetine alone. These findings have implications for patients with depression who may benefit from long-term psychotherapy or combined treatment, or for depressed patients who do not wish to take medications such as fluoxetine.     

Effects on EMG feedback, diazepam and their combination on chronic anxiety.

Although there have been numerous publications on the use of EMG feedback, few controlled studies evaluating its efficacy as a treatment for anxiety have been published. Forty patients with chronic free-floating anxiety were randomly assigned to one of four groups in a 2 x 2 factorial design: EMG feedback plus diazepam, EMG feedback plus diazepam placebo, EMG control (no feedback) plus diazepam and EMG control (no feedback) plus diazepam placebo.During treatment, the effects of EMG feedback plus diazepam were additive in reducing muscular tension. Although all active treatment groups reduced their anxiety after treatment, diazepam-treated subjects (with or without feedback) did less well than other subjects on anxiety measurements, adjuvant medication usage and home practice. The results indicate that EMG feedback treatment without diazepam had a more prolonged therapeutic effect for chronic anxious patients.     

失眠伴抑郁与单纯失眠患者失眠认知行为治疗的疗效分析

目的分析失眠认知行为疗法(cognitive behavioral therapy on insomnia,CBT-i)对失眠伴抑郁患者以及单纯失眠患者的疗效。方法71例符合失眠症诊断的患者,根据贝克抑郁量表(Beck Depression Inventory,BDI)得分分为单纯失眠组(<14分,33例)和失眠伴抑郁组(≥14分,38例)。2组患者每天填写睡眠日记,并给予8周标准的CBT-i治疗,在治疗前(基线)、治疗第4周、治疗第8周、治疗结束后4周(第3个月)、治疗结束后16周(第6个月)采用匹兹堡睡眠质量指数(Pittsburgh Sleep Quality Index,PSQI)、失眠严重程度指数(Insomnia Severity Index,ISI)、BDI、贝克焦虑量表(Beck Anxiety Inventory,BAI)、SF-36健康调查简表对2组患者睡眠质量、抑郁焦虑程度、个人健康状况等进行评估,采用独立样本t检验进行组间比较,采用重复测量方差分析进行各时间点组内比较。结果与基线时比较,单纯失眠组和失眠伴抑郁组第8周、第3个月和6个月随访时入睡潜伏期、睡眠效率、PSQI、ISI、BDI、BAI、SF-36组内比较差异均有统计学意义。失眠伴抑郁组较单纯失眠组在基线、第8周、第3个月和6个月随访时BAI(t=-6.340、-3.301、-3.511、-2.982)、SF-36(t=4.162、3.195、2.022、3.629)评分差异有统计学意义(P<0.01或0.05),2组ISI评分在第6个月随访时差异有统计学意义[(7.3±4.6)分与(4.7±3.4)分,t=-2.044,P=0.048]。2组入睡潜伏期和睡眠效率以及PSQI的评分在第8周、第3个月和6个月随访时与基线的变化量差异均无统计学意义;而2组BAI、BDI评分在第8周与第3个月和6个月随访时与基线的变化量差异有统计学意义。结论CBT-i对失眠伴抑郁患者和单纯失眠患者均有效,且可以缓解失眠伴抑郁患者的抑郁症状以及改善患者生活质量。     

Combined therapy of major depression with concomitant borderline personality disorder: comparison of interpersonal and cognitive psychotherapy.

OBJECTIVE: The combination of antidepressants and brief psychotherapies has been proven more efficacious in treating major depression and is particularly recommended in patients with concomitant personality disorders. We compare the effects of 2 combined therapies, fluoxetine and interpersonal therapy (IPT) or fluoxetine and cognitive therapy (CT), on major depression in patients with borderline personality disorder (BPD). METHOD: Thirty-five consecutive outpatients with a diagnosis of BPD and a major depressive episode (not bipolar and not psychotic) were enrolled. They were randomly assigned to 1 of the 2 combined treatments and treated for 24 weeks. Assessment included a semistructured interview, Clinical Global Impression (CGI) scale, Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Beck Depression Inventory-II (BDI-II), Social and Occupational Functioning Assessment Scale (SOFAS), Satisfaction Profile (SAT-P) for quality of life (QOL), and Inventory of Interpersonal Problems (IIP-64). Statistical analysis was performed using the univariate General Linear Model to calculate the effects of duration and type of treatment. RESULTS: No significant differences between treatments were found at CGI, HDRS, BDI-II, and SOFAS score. Combined treatment with CT had greater effects on HARS score and on psychological functioning factor of SAT-P. Combined treatment with IPT was more effective on social functioning factor of SAT-P and on domains domineering or controlling and intrusive or needy of IIP-64. CONCLUSIONS: Both combined therapies are efficacious in treating major depression in patients with BPD. Differences between CT and IPT concern specific features of subjective QOL and interpersonal problems. These findings lack reliable comparisons and need to be replicated.