Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression

Antidepressant medication is considered the current standard for severe depression, and cognitive therapy is the most widely investigated psychosocial treatment for depression. However, not all patients want to take medication, and cognitive therapy has not demonstrated consistent efficacy across trials. Moreover, dismantling designs have suggested that behavioral components may account for the efficacy of cognitive therapy. The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a randomized placebo-controlled design in adults with major depressive disorder (N = 241). In addition, it examined the importance of initial severity as a moderator of treatment outcome. Among more severely depressed patients, behavioral activation was comparable to antidepressant medication, and both significantly outperformed cognitive therapy. The implications of these findings for the evaluation of current treatment guidelines and dissemination are discussed.     

Relationship of posttreatment decentering and cognitive reactivity to relapse in major depression

Z. V. Segal et al. (2006) demonstrated that depressed patients treated to remission through either antidepressant medication (ADM) or cognitive-behavioral therapy (CBT), but who evidenced mood-linked increases in dysfunctional thinking, showed elevated rates of relapse over 18 months. The current study sought to evaluate whether treatment response was associated with gains in decentering-the ability to observe one's thoughts and feelings as temporary, objective events in the mind-and whether these gains moderated the relationship between mood-linked cognitive reactivity and relapse of major depression. Findings revealed that CBT responders exhibited significantly greater gains in decentering compared with ADM responders. In addition, high post acute treatment levels of decentering and low cognitive reactivity were associated with the lowest rates of relapse in the 18-month follow-up period.     

Impaired divided attention predicts delayed response and risk to relapse in subjects with depressive disorders

BACKGROUND: This study addresses the complex relationship between cognitive function and the course of depression. METHOD: A sample of patients (n=73) in a depressive episode (major depression or bipolar disorder) was tested with a comprehensive battery of attention and executive tasks at both admission and discharge. In addition, response to pharmacological treatment and remission was assessed with standardized rating scales. Nineteen patients, recovered from depression, were re-investigated 6 months after discharge to determine whether specific cognitive parameters were related to subsequent relapse. RESULTS: On admission, patients were impaired in almost all cognitive tasks. At discharge, we found a significant reduction in psychopathology, but only marginal cognitive improvements. Non-responders after 4 weeks of antidepressive medication and subjects who did not achieve remission prior to discharge were specifically impaired in divided attention on admission (p < 0.05). In addition, a trend was found for the association between impaired divided attention at discharge and an elevated risk to relapse (p < 0.10). CONCLUSIONS: We observed generalized cognitive impairment in most cognitive domains in acute depression. Cognitive impairments were still within abnormal ranges at discharge but less distinct. Divided attention performance predicted response to treatment, remission of symptoms, and risk to relapse. Impaired divided attention capacity can be explained either by reduced attentional resources or impaired activation and/or top-down control of attentional resources by the central executive.     

Mechanisms of action in cognitive-behavioral and pharmacological interventions for obesity and bulimia nervosa

In the treatment of obesity, anorexiant medication appears to enhance restraint, presumably through altering internal cues, and facilitates weight loss with behavioral treatment. However, relapse occurs once medication is withdrawn. Antidepressants appear to work similarly, and initial evidence suggests the same limitations. Long-term combined pharmacologic and behavioral treatment, however, may be useful for some individuals not responding positively to behavioral treatment alone. In the treatment of bulimia nervosa, antidepressants appear to enhance restraint, whereas cognitive behavioral treatment decreases restraint. Thus, these modalities appear to be incompatible, and highly restrictive eating is not desirable for those of normal weight. However, for individuals not responding to cognitive-behavioral treatment, long-term pharmacologic treatment may be an alternative, perhaps combined with a more compatible psychological treatment.     

New psychotherapeutic approaches to residual symptoms and relapse prevention in unipolar depression

Relapse and recurrence are vexing problems of unipolar depression. Awareness of their frequent occurrence has led to the development of pharmacological long‐term strategies. A substantial proportion of patients with mood disorders still display residual symptoms upon successful treatment of their illness. Such symptoms were found to entail prognostic value in the prediction of relapse in the entire range of affective disorders. Specific psychotherapeutic strategies for this stage of illness have been developed. One involves cognitive‐behavioral treatment of residual symptoms after successful pharmacological therapy of acute depression. This strategy has resulted in a lower relapse rate at a four‐year follow‐up compared to a clinical management group. The other strategy, based on Ryff's conceptual model, was developed to enhance well‐being (well‐being therapy). Results from recent pilot studies indicate that well‐being therapy may be a promising strategy for decreasing residual symptomatology in affective disorders and thus as a relapse‐preventive strategy. Copyright © 1999 John Wiley & Sons, Ltd.     

行为激活技术对抑郁症的疗效研究

目的 探讨行为激活技术对抑郁症患者的临床疗效.方法 单相抑郁症患者42例随机分为联合治疗组(行为激活技术结合药物治疗)和对照组(单纯药物治疗),疗程10周.分别于治疗前、治疗后以及1年随访结束时采用汉密尔顿抑郁量表(HAMD)和生活质量综合评定问卷(GQOLI- 74)评定临床疗效和生活质量情况.结果 两组的HAM...     

Computerized,interactive, multimedia cognitive-behavioural program for anxiety and depression in general practice

BACKGROUND: Cognitive-behavioural therapy (CBT) brings about significant clinical improvement in anxiety and depression, but therapists are in short supply. We report the first phase of a randomized controlled trial of an interactive multimedia program of cognitive-behavioural techniques, Beating the Blues (BtB), in the treatment of patients in general practice with anxiety, depression or mixed anxiety/depression. METHOD: One hundred and sixty-seven adults suffering from anxiety and/or depression and not receiving any form of psychological treatment or counselling were randomly allocated to receive, with or without medication, BtB or treatment as usual (TAU). Measures were taken on five occasions: prior to treatment, 2 months later, and at 1, 3 and 6 months follow-up using the Beck Depression Inventory, Beck Anxiety Inventory and Work and Social Adjustment Scale. RESULTS: Patients who received BtB showed significantly greater improvement in depression and anxiety compared to TAU by the end of treatment (2 months) and to 6 months follow-up. Symptom reduction was paralleled by improvement in work and social adjustment. There were no interactions of BtB with concomitant pharmacotherapy or duration of illness, but evidence, on the Beck Anxiety Inventory only, of interaction with primary care practice. Importantly, there was no interaction between the effects of BtB and baseline severity of depression, from which we conclude that the effects of the computer program are independent of starting level of depression. CONCLUSIONS: These results demonstrate that computerized interactive multimedia cognitive-behavioural techniques under minimal clinical supervision can bring about improvements in depression and anxiety, as well as in work and social adjustment, with and without pharmacotherapy and in patients with pre-treatment illness of durations greater or less than 6 months. Thus, our results indicate that wider dissemination of cognitive-behavioural techniques is possible for patients suffering from anxiety and/or depression.     

矫正体验心理疗法治疗抑郁症的对照研究

目的 探讨提高治疗抑郁症疗效的方法.方法 对首次住院诊断为抑郁症的病例,采用随机的方法分入贝克认知疗法组和矫正体验心理疗法组进行约10周对照研究,随访1年,并采用Hamilton抑郁量表和Hamilton焦症量表对治疗前后及随访进行评定.结果 治疗前后比较,两组焦虑抑郁分均有显著下降(P＜0.01),治疗结束与随访时两组间评分差异有显著性;两组间治愈率差异有显著性(分别为41.67%及52.27%,P＜0.05).结论 2种方法对抑郁症治疗均有效,但矫正体验心理疗法治疗抑郁症疗效更为明显.     

Unlinking negative cognition and symptoms of depression: evidence of a specific treatment effect for cognitive therapy

In this study, the authors examined whether cognitive therapy alters the association between negative cognition and symptoms of depression. Participants were recruited during psychiatric hospitalization for depression. Following discharge, they were randomly assigned to 6 months of outpatient treatment. Treatment consisted of pharmacotherapy either alone or in combination with cognitive therapy and/or family therapy. Following this 6-month treatment period, negative cognition and symptoms of depression were assessed monthly for 1 year. Hierarchical linear modeling indicated that the association between negative cognition and depression during follow-up was weaker for patients randomized to cognitive therapy than for patients who did not receive cognitive therapy. Cognitive therapy appeared to unlink negative cognition and symptoms of depression to a greater extent than other forms of treatment.     

Enhanced treatment for depression in primary care: long-term outcomes of a psycho-educational prevention program alone and enriched with psychiatric consultation or cognitive behavioral therapy

BACKGROUND: The long-term outcome of major depression is often unfavorable, and because most cases of depression are managed by general practitioners (GPs), this places stress on the need to improve treatment in primary care. This study evaluated the long-term effects of enhancing the GP's usual care (UC) with three experimental interventions. METHOD: A randomized controlled trial was conducted from 1998 to 2003. The main inclusion criterion was receiving GP treatment for a depressive episode. We compared: (1) UC (n=72) with UC enhanced with: (2) a psycho-educational prevention (PEP) program (n=112); (3) psychiatrist-enhanced PEP (n=37); and (4) brief cognitive behavioral therapy followed by PEP (CBT-enhanced PEP) (n=44). We assessed depression status quarterly during a 3-year follow-up. RESULTS: Pooled across groups, depressive disorder-free and symptom-free times during follow-up were 83% and 17% respectively. Almost 64% of the patients had a relapse or recurrence, the median time to recurrence was 96 weeks, and the mean Beck Depression Inventory (BDI) score over 12 follow-up assessments was 9.6. Unexpectedly, PEP patients had no better outcomes than UC patients. However, psychiatrist-enhanced PEP and CBT-enhanced PEP patients reported lower BDI severity during follow-up than UC patients [mean difference 2.07 (95% confidence interval (CI) 1.13-3.00) and 1.62 (95% CI 0.70-2.55) respectively] and PEP patients [2.37 (95% CI 1.35-3.39) and 1.93 (95% CI 0.92-2.94) respectively]. CONCLUSIONS: The PEP program had no extra benefit compared to UC and may even worsen outcome in severely depressed patients. Enhancing treatment of depression in primary care with psychiatric consultation or brief CBT seems to improve the long-term outcome, but findings need replication as the interventions were combined with the ineffective PEP program.     

Extreme nonresponse in cognitive therapy: can behavioral activation succeed where cognitive therapy fails?

In a recent placebo-controlled comparison, behavioral activation was superior to cognitive therapy in the treatment of moderate to severely depressed adults. Moreover, a subset of patients exhibited a pattern of extreme nonresponse to cognitive therapy on self-reports of depression not evident on the clinician ratings. These patients were severely depressed, functionally impaired, and had primary support group problems; most also described themselves as having life-long depressions. Comparable numbers of patients with such characteristics were assigned to behavioral activation, indicating that randomization did not fail, and most instances occurred in the context of adequate cognitive therapy. If this pattern of self-reported extreme nonresponse to cognitive therapy replicates, it would suggest that there might be a subset of patients who see themselves as doing better with sustained attention to behavior change in time-limited treatment.     

Comparing outcomes in chronic depression following inpatient psychotherapy for patients continuing versus discontinuing antidepressant medication

Research indicates that combination of psychotherapy and antidepressant medication (ADM) provides cumulative effects and thus outperforms monotherapy in treating chronic depression. In this quasi-experimental study, we explored symptom change for patients with chronic depression treated with ADM when presenting for a 12-week psychotherapeutic inpatient treatment programme. We compared outcomes through treatment and follow-up of patients who continued medication with those who discontinued. We also tested possible moderator effects of initial depression severity on change between the groups. Based on prior research, we hypothesized that combination treatment would yield better results (i.e., more reduction in depression). Patients (N = 112) were referred from general practitioners or local secondary health care. Outcome was measured by Beck Depression Inventory-II (BDI-II), and comparisons were carried out using multilevel modelling. Although 35 patients discontinued ADM during treatment, 77 continued. Both continuers and discontinuers had a significant treatment effect that was maintained at 1-year follow-up. There was no difference in outcome between continuers and discontinuers of ADM. Patients with severe depression had significantly more symptom improvement than patients with moderate depression, but depression severity did not affect outcomes across continuers and discontinuers of ADM differently. The results could indicate that patients had developed resistance and/or tolerance to the prophylactic effects of medication and that ADM did not contribute to the reduction of depressive symptoms. The findings may also indicate that psychotherapy alone in some instances can be a viable alternative to continued combined treatment. Clinicians should carefully assess benefits of patients' ongoing use of antidepressant medication when entering psychotherapy.     

A 15-year analysis of early and late autologous hematopoietic stem cell transplant in relapsed, aggressive, transformed, and nontransformed follicular lymphoma.

Autologous stem cell transplant (ASCT) has been shown to be an effective treatment for follicular lymphoma (FL). We explored our experience in ASCT for FL among all patients treated over a 15-year period from diagnosis through their entire treatment history including relapse post ASCT. All patients who underwent an unpurged ASCT for relapsed, advanced FL between June 1990 and December 2000 were analyzed. After salvage therapy they received melphalan/etoposide/total body irradiation, BCNU, etoposide, cytarabine, melphalan (BEAM), or cyclophosphamide BCNU etoposide (CBV) as conditioning for the ASCT. One hundred thirty-eight patients with a median age of 48 years and a median follow-up of 7.6 years were analyzed. The majority were of the subtype grade 1, nontransformed (FL-NT), having had 1 prior chemotherapy. The progression-free (PFS) and overall survival (OS) of the FL-NT at 10 years were 46% and 57%, respectively, and at 5 years for the transformed (FL-T) were 25% and 56%, respectively, of which only the PFS was significantly different (P=.007). The median OS from diagnosis was 16 years for the FL-NT. ASCT positively altered the trend of shorter remissions with subsequent chemotherapies, and there was no difference in OS between those who had 1, 2, or >2 chemotherapies prior to ASCT. Salvage therapy for relapse post ASCT was effective (OS>1 year) in a third of patients. Unpurged ASCT is an effective tool in the treatment of relapsed, aggressive FL-NT and FL-T, is superior to retreatment with standard chemotherapy, is effective at various stages of treatment, is likely to have a beneficial influence on the natural history of this disease, and the disease is amenable to salvage therapy post-ASCT relapse.     

Cognitive therapy with depressed inpatients: specific effects on dysfunctional cognitions

Specificity of cognitive change following cognitive therapy for depression was assessed in 39 depressed inpatients who completed either a standard inpatient treatment (pharmacotherapy and milieu management) or the standard treatment plus cognitive therapy. Following treatment, patients in both groups endorsed fewer dysfunctional cognitions on 2 of 4 measures of cognitive distortion. Compared with patients receiving only the standard treatment, patients also receiving cognitive therapy reported less hopelessness and fewer cognitive biases at posttreatment and 6- and 12-month follow-up assessments and fewer dysfunctional attitudes at the 6-month follow-up. Treatment effects for dysfunctional cognitions were found even though the treatment groups did not differ in depression severity, suggesting that results did not reflect state-dependent differences between treatments secondary to difference in depression.     

Randomized trial of a population-based care program for people with bipolar disorder

BACKGROUND: Despite the availability of efficacious medications and psychotherapies, care of bipolar disorder in everyday practice is often deficient. This trial evaluated the effectiveness of a multi-component care management program in a population-based sample of people with bipolar disorder. METHOD: Four hundred and forty-one patients treated for bipolar disorder during the prior year were randomly assigned to continued usual care or usual care plus a systematic care management program including: initial assessment and care planning, monthly telephone monitoring including brief symptom assessment and medication monitoring, feedback to and coordination with the mental health treatment team, and a structured group psychoeducational program--all provided by a nurse care manager. Blinded quarterly assessments generated week-by-week ratings of severity of depression and mania symptoms using the Longitudinal Interval Follow-Up Evaluation. RESULTS: Participants assigned to the intervention group had significantly lower mean mania ratings averaged across the 12-month follow-up period (Z= 2.44, p=0.015) and approximately one-third less time in hypomanic or manic episode (2.59 weeks v. 1.69 weeks). Mean depression ratings across the entire follow-up period did not differ significantly between the two groups, but the intervention group showed a greater decline in depression ratings over time (Z statistic for group-by-time interaction = 1.98, p = 0.048). CONCLUSIONS: A systematic care program for bipolar disorder significantly reduces risk of mania over 12 months. Preliminary results suggest a growing effect on depression over time, but longer follow-up will be needed.     

A meta-analysis of psychotherapy and medication in unipolar depression and dysthymia

BACKGROUND: There remains considerable disagreement regarding the relative efficacy of psychotherapy and medication across types of depression. METHOD: We used random effects meta-analysis to examine the relative efficacy of psychotherapy vis-à-vis medication at post-treatment and follow-up. We also estimated the relative efficacy of continued medication versus discontinued psychotherapy. As twenty-eight studies (39 effects, n=3381) met inclusion criteria, we were able to conduct an adequately powered test of between-study heterogeneity and examine if the type of depression influenced relative efficacy. RESULTS: Psychotherapy and medication were not significantly different at post-treatment, however effect sizes were not consistent. Although there was no association between severity and relative efficacy, a small but significant advantage for medications in the treatment of dysthymia did emerge. However, psychotherapy showed a significant advantage over medication at follow-up and this advantage was positively associated with length of follow-up. Moreover, discontinued acute phase psychotherapy did not differ from continued medication at follow-up. LIMITATIONS: Limitations included relatively fewer studies of severe and chronic depression, as well as dysthymia. In addition, only a minority of studies reported follow-up data. CONCLUSIONS: Our results indicated that both psychotherapy and medication are viable treatments for unipolar depression and that psychotherapy may offer a prophylactic effect not provided by medication. However, our analyses diverged from previous findings in that effects were not consistent and medication was significantly more efficacious than psychotherapy in the treatment of dysthymia.     

Preventing relapse/recurrence in recurrent depression with cognitive therapy: a randomized controlled trial

This article reports on the outcome of a randomized controlled trial of cognitive group therapy (CT) to prevent relapse/recurrence in a group of high-risk patients diagnosed with recurrent depression. Recurrently depressed patients (N = 187) currently in remission following various types of treatment were randomized to treatment as usual, including continuation of pharmacotherapy, or to treatment as usual augmented with brief CT. Relapse/recurrence to major depression was assessed over 2 years. Augmenting treatment as usual with CT resulted in a significant protective effect, which intensified with the number of previous depressive episodes experienced. For patients with 5 or more previous episodes (41% of the sample), CT reduced relapse/recurrence from 72% to 46%. Our findings extend the accumulating evidence that cognitive interventions following remission can be useful in preventing relapse/recurrence in patients with recurrent depression.     

Circulating immune complexes, complement and complement component levels in childhood Hodgkin's disease.

Serum levels of circulating immune complexes (CIC) assayed by the Raji cell radioimmunoassay, total haemolytic complement (TCH50), Clq and C3 were correlated with clinical stage, histological type, age, sex and treatment of eighty-six children with Hodgkin's disease over a period of 4 years. Most significant findings were the changes of levels of CIC, TCH50, Clq and C3 during disease activity and following treatment. Significant perturbations were also seen in association with relapse. Levels of C and CIC were significantly elevated (P less than 0.001) at the time of diagnosis prior to splenectomy and/or any treatment. In the group before treatment, 81 percent of CIC levels were above 16 micrograms/ml with a maximum value of 1120 micrograms/ml. During treatment 33 percent were still above normal with a maximum of 320 micrograms/ml. Within 1 year after cessation of treatment, 37 percent also remained above normal levels with a maximum of 240 micrograms/ml. At relapse prior to treatment, 63 percent were again elevated with a maximum of 1280 micrograms/ml. The most significant difference on TCH50 levels relates to treatment periods. Sera of patients with active disease who are previously untreated show elevation of TCH50 levels (P less than 0.001) (average 127 CH50 mu/ml. During and after treatment eht TCH50 levels drop to 96 and 102 CH50 mu/ml, as compared to normal control of 100 CH50 mu/ml. In sera of patients at the first, second or third relapse, the combined TCH50 levels are significantly different from controls and across treatment periods (P less than 0.005).     

A pilot study of cognitive therapy in bipolar disorders

BACKGROUND: The efficacy and effectiveness of cognitive therapy (CT) is well established for unipolar disorders, but little is known about its utility in bipolar disorders. This study aimed to explore the feasibility and efficacy of using CT as an adjunct to usual psychiatric treatment in this patient population. METHOD: Subjects referred by general adult psychiatrists were assessed by and independent rater and then randomly allocated to immediate CT (N = 21) or 6-month waiting-list control, which was then followed by CT (N = 21). Observer and self-ratings of symptoms and functioning were undertaken immediately prior to CT, after a 6-month course of CT and a further 6-months later. Data on relapse and hospitalization rates in the 18 months before and after commencing CT were also collected. RESULTS: At 6-month follow-up, subjects allocated to CT showed statistically significantly greater improvements in symptoms and functioning as measured on the Beck Depression Inventory, the Internal State Scale, and the Global Assessment of Functioning than those in the waiting-list control group. In the 29 patients who eventually received CT, relapse rates in the 1 8 months after commencing CT showed a 60 % reduction in comparison with the 18 months prior to commencing CT. Seventy per cent of subjects who commenced therapy viewed CT as highly acceptable. CONCLUSION: Although the results of this study are encouraging, the use of CT in subjects with bipolar disorders is more complex than in unipolar disorders and requires a high level of therapist expertise. The therapy may prove to be particularly useful in the treatment of bipolar depression.     

Combined Psychotherapy and Pharmacotherapy for the Treatment of Major Depressive Disorder

Studies comparing the efficacy of combined psychotherapy and pharmacotherapy to single treatment (i.e., either psychotherapy or pharmacotherapy alone) for major depression have not found consistent differences in outcome, resulting in a range of conclusions regarding the efficacy of combined treatment. In order to clarify the efficacy of combined treatment for depression, the authors conducted both a meta-analytic and qualitative review. Our findings suggest that combined treatment is associated with a small improvement in efficacy, and that this finding appears consistent across studies. Trends in the literature suggest that adding psychotherapy to antidepressant medication may be particularly efficacious among chronic or severely depressed patients. Further, adding cognitive-behavioral therapy to medication may be particularly efficacious in preventing relapse, particularly among individuals discontinuing medication use. The authors propose an illness-cognition model for better understanding outcomes in combined treatment.