Cognitive reactivity to sad mood provocation and the prediction of depressive relapse

CONTEXT: Episode remission in unipolar major depression, while distinguished by minimal symptom burden, can also be a period of marked sensitivity to emotional stress as well as an increased risk of relapse. OBJECTIVE: To examine whether mood-linked changes in dysfunctional thinking predict relapse in recovered patients who were depressed. DESIGN: In phase 1 of this study, patients with major depressive disorder were randomly assigned to receive either antidepressant medication or cognitive behavior therapy. In phase 2, patients who achieved clinical remission underwent sad mood provocation and were then observed with regular clinical assessments for 18 months. SETTING: Outpatient psychiatric clinics at the Centre for Addiction and Mental Health, Toronto, Ontario. PARTICIPANTS: A total of 301 outpatients with major depressive disorder, aged 18 to 65 years, participated in phase 1 of this study and 99 outpatients with major depressive disorder in remission, aged 18 to 65 years, participated in phase 2. MAIN OUTCOME MEASURE: Occurrence of a relapse meeting DSM-IV criteria for a major depressive episode as assessed by the longitudinal interval follow-up evaluation and a Hamilton Depression Rating Scale score of 16 or greater. RESULTS: Patients who recovered through antidepressant medication showed greater cognitive reactivity following the mood provocation than those who received cognitive behavior therapy. Regardless of type of prior treatment, the magnitude of mood-linked cognitive reactivity was a significant predictor of relapse over the subsequent 18 months. Patients whose mood-linked endorsement of dysfunctional attitudes increased by a minimum of 8 points had a significantly shorter time to relapse than those whose scores were not as elevated. CONCLUSIONS: The vulnerability of remitted depressed patients for illness relapse may be related to the (re)activation of depressive thinking styles triggered by temporary dysphoric states. This is the first study to link such differences to prognosis following successful treatment for depression. Further understanding of factors predisposing to relapse/recurrence in recovered patients may help to shorten the potentially lifelong course of depression.     

Severity of depression and response to cognitive behavior therapy

OBJECTIVE: The authors studied the relationship between clinical severity of depression and response to cognitive behavior therapy. METHOD: Fifty-nine outpatients with major depression with endogenous features, according to Research Diagnostic Criteria, were stratified into more severe (score of 20 or more on the Hamilton Rating Scale for Depression; N = 38) or less severe (Hamilton score of 19 or less; N = 21) subgroups. Patients were treated with a 16-week, 20-session cognitive behavior therapy protocol. Outcome was assessed with the Hamilton scale, the Global Adjustment Scale, and the Beck Depression Inventory. RESULTS: The more severe group was significantly more symptomatic across the 16-week protocol and had a significantly lower response rate on the Beck inventory (50% versus 81%). However, the groups did not significantly differ at end point on any of the three measures, and they showed comparable rates of symptomatic improvement (i.e., percent change in scores and interactions between severity classification and time). CONCLUSIONS: These results partially replicate the National Institute of Mental Health's Treatment of Depression Collaborative Research Program's findings of poorer response to cognitive behavior therapy in patients with Hamilton scale scores of 20 or more. However, both groups experienced robust and clinically significant reductions in depressive symptoms, and the response of the more severe patients in the current study could hardly be considered poor. While these findings do not support the view that a Hamilton scale score of 20 or more is a relative contraindication for cognitive behavior therapy, the symptoms of the more severely depressed patients did tend to remit less completely (particularly on the Beck inventory) and thus these patients may benefit from a more intensive or extended course of therapy.     

Cognitive therapy and pharmacotherapy for depression. Sustained improvement over one year

Seventy patients with nonbipolar affective disorder who completed a 12-week course of either cognitive therapy (CT), pharmacotherapy, CT plus active placebo, or CT plus pharmacotherapy were assessed one month, six months, and one year after termination of active treatment. Of the 44 patients who had originally responded to treatment, 16 relapsed as defined by reentry into treatment or by self-reported depression scores in the moderately depressed range. Twenty-eight patients remained well during the one-year follow-up. Patients with relatively high levels of remaining depressive symptoms on completion of treatment relapsed more often than those who had little or no residual depression. Further, at treatment termination, patients who relapsed had significantly higher scores on a measure of dysfunctional attitudes. Patients who had received CT (with or without tricyclic antidepressants) were less likely to relapse in the one-year follow-up period than patients who received pharmacotherapy.     

Efficacy of combined,sequential and crossover psychotherapy and pharmacotherapy in improving outcomes in depression

There is a growing recognition that relapse and recurrence after the successful treatment of major depression is a common and debilitating outcome that has massive social costs. Although many patients achieve a sustained recovery with maintenance pharmacotherapy, the long-term outcome for a significant proportion of patients is still poor. The purpose of this review is to evaluate the role of combined psychological and pharmacological therapies in minimizing relapse and recurrence in the treatment of depression. Three approaches have been investigated: concurrent treatment, sequential treatment and crossover treatment. Concurrent therapy is as effective as monotherapy for the treatment of mild-to-moderate depressive disorder and shows evidence of a potential treatment advantage in cases where depression is more severe. Consecutive sequencing of pharmacotherapy and psychotherapy has demonstrated some benefit for both the conversion of partial to full response and the prevention of relapse and recurrence, especially in more severely depressed patients. Crossover treatments during the maintenance phase (i.e., switching patients from one treatment to a second after an adequate response to the first) show evidence of being beneficial in preventing relapse and recurrence. Variants of cognitive therapy that have been modified to specifically address residual symptoms in patients who have recovered from depression appear to be the most effective. A review of the studies to date indicates that cognitive therapy may play a role in improving remission rates and decreasing relapse and recurrence rates. Although most studies are small, there is a consistent suggestion of superior prophylaxis for patients receiving some type of sequenced or crossover treatment in which the delivery of antidepressant medication and structured antidepressant psychotherapy is combined. These approaches warrant greater attention; they may present another route for enhancing long-term recovery from major depression.     

One-year outcome of psychotic depression after successful electroconvulsive therapy

BACKGROUND: Psychotic depression is thought to have a higher relapse frequency after electroconvulsive therapy (ECT) compared with nonpsychotic depression, although this observation is contradicted by previous studies that have found the opposite. In this study, the 1-year risk of relapse after successful ECT was determined prospectively in patients with psychotic depression and compared with the risk of relapse observed for depressed patients without psychotic features. METHOD: Fifty-nine responders to ECT (a decrease in Hamilton Rating Scale for Depression [HAM-D] score > or = 50%) were followed for 1 year: 29 with and 30 without psychotic features. Relapse was defined as meeting DSM-IV criteria for major depressive disorder and a HAM-D score > or = 16. The frequency of relapse after 4 and 12 months was compared between both samples, adjusted for the co-variables duration of the index episode and type of post-ECT pharmacotherapy. RESULTS:: At both 4 and 12 months after ECT, instances of relapse were significantly lower in patients with psychotic depression compared with nonpsychotic patients: 3/28 (11%) versus 16/27 (59%) and 4/27 (15%) versus 19/28 (68%), respectively. CONCLUSIONS: The main finding of the present study is the favorable 1-year outcome for patients with psychotic depression after response to ECT with a trend toward the same result at 4 months. The 1-year outcome of the total sample is also more favorable than expected.     

Six-year outcome of cognitive behavior therapy for prevention of recurrent depression

OBJECTIVE: A paucity of studies use nonpharmacological strategies for preventing recurrence in depression. Cognitive behavior treatment of residual symptoms was found to yield a significantly lower relapse rate than clinical management in recurrent depression at a 2-year follow-up. The objective of this investigation was to provide a 6-year follow-up of cognitive behavior treatment versus clinical management. METHOD: Forty patients with recurrent major depression who had been successfully treated with antidepressant drugs were randomly assigned to either cognitive behavior treatment of residual symptoms (supplemented by lifestyle modification and well-being therapy) or clinical management. In both groups, antidepressant drugs were tapered and discontinued. A 6-year follow-up was undertaken. During this period, no antidepressant drugs were used unless a relapse ensued. RESULTS: Cognitive behavior treatment resulted in a significantly lower relapse rate (40%) at a 6-year follow-up than did clinical management (90%). When multiple recurrences were considered, the group that received cognitive behavior treatment had a significantly lower number of relapses in comparison with the clinical management group. CONCLUSIONS: The results suggest that the sequential use of cognitive behavior treatment after pharmacotherapy may improve the long-term outcome in recurrent depression. A significant proportion of patients with recurrent depression might be able to withdraw from medication successfully and to stay well for at least 6 years with a focused course of psychotherapy.     

Prevention of relapse in residual depression by cognitive therapy: a controlled trial

BACKGROUND: Previous studies indicate that depressed patients with partial remission and residual symptoms following antidepressant treatment are common and have high rates of relapse. There is evidence that cognitive therapy may reduce relapse rates in depression. METHODS: One hundred fifty-eight patients with recent major depression, partially remitted with antidepressant treatment (mean daily doses equivalent to 185 mg of amitriptyline or 33 mg of fluoxetine) but with residual symptoms of 2 to 18 months' duration, were included in a controlled trial. Subjects were randomized to receive clinical management alone or clinical management plus cognitive therapy for 16 sessions during 20 weeks, with 2 subsequent booster sessions. Subjects were assessed regularly throughout the 20 weeks' treatment and for a further year. They received continuation and maintenance antidepressants at the same dose throughout. RESULTS: Cognitive therapy reduced relapse rates for acute major depression and persistent severe residual symptoms, in both intention to treat and treated per protocol samples. The cumulative relapse rate at 68 weeks was reduced significantly, from 47% in the clinical management control group to 29% with cognitive therapy (hazard ratio 0.54; 95% confidence interval, 0.32-0.93; intention to treat analysis). Cognitive therapy also increased full remission rates at 20 weeks but did not significantly improve symptom ratings. CONCLUSION: In this difficult-to-treat group of patients with residual depression who showed only partial response despite antidepressant treatment, cognitive therapy produced worthwhile benefit.     

Kognitiv terapi eller psykofarmakologisk behandling ved depresjoner? En kritisk vurdering av behandlingseffekt

Martinsen EW. Cognitive therapy or psychopharmacologic treatment of depressions? A critical evaluation of treatment effect.

A review of controlled studies comparing cognitive therapy and cyclic antidepressant agents (CA) showed that all studies addressed the treatment of nonbipolar DSM-III-R major depression without psychotic or melancholic features. On an average, cognitive therapy and CA seemed to be equally effective. Cognitive therapy tended to be better for the less severely depressed patients, while CA was superior for those most severely depressed. The combined treatment tended to be more effective than either of the two used singly, but this effect was not great. Patients who received cognitive therapy during a depressive episode had reduced risk of relapse; some studies indicated that the relapse rate was reduced to half. This is the most promising finding with regard to cognitive therapy. The number of studies is small, however, and more well-designed studies are needed. The implications for clinical practice and research are discussed.     

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.     

Factors predicting the relapse of depression in old age

BACKGROUND: Studies in mixed-aged populations show differences between the predictors of a relapse and those of a long-term course of depression, supporting the hypothesis about similar differences among the aged. AIM: The aim was to identify the factors predicting or related to a relapse of depression among the Finnish elderly having recovered from depression during treatment. MATERIAL AND METHODS: The population consisted of 70 depressed (DSM-III criteria) elderly (60 yr-) Finns having recovered from depression during treatment as determined 15 months after baseline. By the 4-year follow-up after the recovery, 20 patients had relapsed and 50 persons were non-depressed. RESULTS: The logistic regression model showed major depression and psychomotor retardation to be independent predictors. Relapses were not related to stressors in life or physical illnesses occurring during the follow-up. CONCLUSIONS: Major depressive elderly patients have a high risk for relapses without the occurrence of the stressors or physical illnesses. In clinical practice, major depressive elderly patients should be followed up in order to detect and treat potential relapses as early as possible. Cooperation between psychiatrists and general practitioners is needed in the follow-up. Theoretically, the results suggest the assumption of a biochemical aetiology of major depression.     

Mindfulness predicts relapse/recurrence in major depressive disorder after mindfulness-based cognitive therapy

Empirical evidence for the effectiveness of mindfulness-based cognitive therapy (MBCT) is encouraging. However, data concerning the role of mindfulness in its relapse preventive effect are lacking. In our study, 25 formerly depressed patients received MBCT. Mindfulness was assessed before and immediately after MBCT using the Mindful Attention and Awareness Scale. Mindfulness significantly increased during MBCT, and posttreatment levels of mindfulness predicted the risk of relapse/recurrence to major depressive disorder in the 12-month follow-up period. Mindfulness predicted the risk of relapse/recurrence after controlling for numbers of previous episodes and residual depressive symptoms. The results provide preliminary evidence for the notion that mindfulness is an important factor in relapse prevention in major depression.     

认知疗法合并艾司西酞普兰治疗女性抑郁症患者的疗效

目的:比较艾司西酞普兰合并认知治疗与单用艾司西酞普兰对女性抑郁症患者的疗效。方法:60例女性抑郁症患者随机分为研究组(艾司西酞普兰合并认知治疗组)30例,对照组(单用艾司西酞普兰组)30例,治疗8周。治疗前及治疗1、2、4和8周分别采用汉密尔顿抑郁量表(HAMD)评定疗效。结果:治疗2周开始,两组HAMD评分均显著下降。研究组治疗1周HAMD明显下降。研究组较对照组HAMD下降更显著。两组不良反应差异无显著性。结论:艾司西酞普兰合并认知治疗对女性抑郁症患者疗效明显,安全性高。     

Course of depressive symptoms over follow-up. Findings from the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

We studied the course of depressive symptoms during an 18-month naturalistic follow-up period for outpatients with Major Depressive Disorder treated in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. The treatment phase consisted of 16 weeks of randomly assigned treatment with the following: cognitive behavior therapy, interpersonal therapy, imipramine hydrochloride plus clinical management (CM), or placebo plus CM. Follow-up assessments were conducted at 6, 12, and 18 months after treatment. Of all patients entering treatment and having follow-up data, the percent who recovered (8 weeks of minimal or no symptoms following the end of treatment) and remained well during follow-up (no Major Depressive Disorder relapse) did not differ significantly among the four treatments: 30% (14/46) for those in the cognitive behavior therapy group, 26% (14/53) for those in the interpersonal therapy group, 19% (9/48) for those in the imipramine plus CM group, and 20% (10/51) for those in the placebo plus CM group. Among patients who had recovered, rates of Major Depressive Disorder relapse were 36% (8/22) for those in the cognitive behavior therapy group, 33% (7/21) for those in the interpersonal therapy group, 50% (9/18) for those in the imipramine plus CM group, and 33% (5/15) for those in the placebo plus CM group. The major finding of this study is that 16 weeks of these specific forms of treatment is insufficient for most patients to achieve full recovery and lasting remission. Future research should be directed at improving success rates of initial and maintenance treatments for depression.     

Residual symptoms in depressed patients who respond acutely to fluoxetine

BACKGROUND: Antidepressants have unequivocal efficacy as compared with placebo, but many patients have residual symptoms despite a robust response to antidepressant therapy. The purpose of this study is to assess residual symptoms in outpatients who respond acutely to fluoxetine. METHOD: Two hundred and fifteen outpatients with major depressive disorder as assessed with the Structured Clinical Interview for DSM-III-R (SCID-P) were treated openly with fluoxetine 20 mg/day for 8 weeks. One hundred and eight (50.2%) were considered full responders (final 17-item Hamilton Rating Scale for Depression [HAM-D] score < or =7). Percentages of full responders who continued to have subthreshold or full major depressive disorder symptoms were calculated. The relationship between residual symptoms and Axis I and Axis II (assessed with SCID-II for personality disorders) comorbidity was assessed. RESULTS: Of the 108 responders, 19 (17.6%) had no subthreshold or threshold SCID-P major depressive disorder symptoms, while 28 (25.9%) had 1 symptom, and 61 (56.5%) had 2 or more symptoms. No statistically significant relationships were found between number of residual symptoms and selected Axis I comorbid conditions or total number of Axis II disorders. CONCLUSION: Less than 20% of full responders to fluoxetine by HAM-D criteria were free of all SCID-P subthreshold and threshold major depressive disorder symptoms after 8 weeks of treatment. While depressed patients benefit from antidepressants, most continue to have some symptoms of depression. The high prevalence of residual symptoms among antidepressant responders suggests the need for further study including whether residual symptoms abate with longer treatment or increased dose of fluoxetine. Other strategies, such as cognitive behavioral therapy, may be needed to address residual symptoms.     

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.     

表达性艺术治疗对抑郁症残留症状疗效随机对照研究

目的 探讨艾司西酞普兰合并表达性艺术治疗对于抑郁症残留症状的疗效.方法 60例单用艾司西酞普兰治疗6周后存在残留症状的抑郁症患者被随机分为研究组（n=30）和对照组（n=30）,分别给予为期4周的艾司西酞普兰合并表达性艺术治疗和单用艾司西酞普兰治疗.在基线期和4周末采用汉密尔顿抑郁量表（Hamilton DepressionScale-17,HAMD-17）、汉密尔顿焦虑量表（Hamilton anxiety scale,HAMA）评定疗效.结果 基线期研究组和对照组HAMD-17、HAMA评分无统计学差异（P＞0.05）;治疗后第4周末,研究组HAMD-17减分显著高于对照组（P =0.009）,研究组HAMA减分显著高于对照组（P =0.000）.结论 艾司西酞普兰合并表达性艺术治疗较单用艾司西酞普兰能更好地改善抑郁症的残留症状.     

Placebo response and antidepressant response.

OBJECTIVE: Much of the response to an antidepressant is the result of placebo response. The placebo response embedded in drug response confounds studies seeking to identify brain mechanisms essential for pharmacologic response. Exclusion of patients who fail to meet entry criteria at the end of a placebo lead-in phase has been inadequate to reduce the effect of placebo during pharmacologic trials. This study focused on the placebo lead-in phase and examines whether change in severity of depression during placebo lead-in predicts change in depressive symptoms during antidepressant treatment. METHOD: The subjects were patients aged 60-85 years with nonpsychotic unipolar major depression not attributed to dementing disorders, medical illnesses, or drugs causing depression and had a 24-item Hamilton Depression Rating Scale score of 18 or greater. After a two-week placebo lead-in, subjects with Hamilton Depression Rating Scale score of 18 or greater received 10 mg escitalopram for 12 weeks. RESULTS: Worsening or limited change in depression during placebo treatment predicted improvement in depressive symptoms during escitalopram treatment. Limited change in anxiety, melancholia, helplessness, and paranoia during placebo treatment were the strongest predictors of improvement in depression while on escitalopram. CONCLUSIONS: These findings, if replicated, may be used to characterize depressed older patients likely to respond to the pharmacologic action of antidepressants rather than the placebo response embedded in drug trials and thus improve the methodology of biomarker studies of antidepressant response. On a clinical level, depressed older patients who improve during a prolonged evaluation may be candidates for nonpharmacologic treatments because their drug response may be limited.     

Relationships between major depressive disorder and comorbid anxiety and personality disorders

OBJECTIVE: The aim of the study was to examine whether comorbid anxiety disorders influence depressed patients' likelihood of meeting criteria for a personality disorder (PD) and whether comorbid anxiety disorders influence the stability of the PDs in patients with remitted depression. METHODS: The initial sample consisted of 373 outpatients who met criteria for major depressive disorder (MDD) (by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition-Patient Edition) and who were enrolled in the 8-week acute treatment phase of a study of fluoxetine for MDD. Sixty-four subjects who responded to fluoxetine treatment in the acute phase met criteria for remission throughout a 26-week continuation phase during which they remained on fluoxetine with or without cognitive behavioral therapy. Stability of PDs was defined as meeting criteria for a PD at both beginning and end point of the continuation treatment phase. RESULTS: Before fluoxetine treatment, anxious depressed patients (defined as meeting criteria for MDD as well as at least one comorbid anxiety disorder) were significantly more likely to meet criteria for any comorbid PD diagnosis compared with depressed patients without comorbid anxiety disorders. In particular, there was a significant relationship between the presence of Cluster A and C PDs and the presence of anxious depression at baseline before antidepressant treatment. After successful treatment of MDD, we found a significant relationship between anxious depression diagnosed at baseline and the stability of a Cluster C PD diagnosis. CONCLUSION: Anxious depression may place patients at greater risk of having a PD diagnosis, especially one from Cluster A or C. Once the depression remits, patients who initially met criteria for anxious depression may be more likely to maintain a Cluster C PD diagnosis compared with patients initially diagnosed with MDD alone.