Early-onset Chronic Depression Research Articles

Longitudinal Clusters of Long-Term Trajectories in Patients with Early-Onset Chronic Depression: 2 Years of Naturalistic Follow-Up after Extensive Psychological Treatment

Introduction: In clinical trials, mostly group-level treatment effects of repeated cross-sectional measures are analyzed. However, substantial heterogeneity regarding individual symptom profiles and the variability of treatment effects are often neglected, especially over the long-term course. To provide effective personalized treatments, investigations of these characteristics are urgently needed. Methods: Depression severity ratings over 104 weeks of follow-up after year-long treatment with the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or Supportive Psychotherapy (SP) were analyzed. Longitudinal cluster analysis and multinomial logistic regression analysis were conducted to investigate intraindividual trajectories from one of the largest psychotherapy trials in early-onset chronic depression. Results: Two-year post-study-treatment trajectories of N = 188 patients with early-onset chronic depression were grouped into four prototypical clusters. Overall, 16.0% of patients remitted (cluster 1) and most of them did not receive any treatment during the 2-year follow-up. However, 84.0% of patients continued to experience subthreshold (37.2% cluster 2) or major depressive symptoms (46.8% clusters 3–4) and spent on average more than half of the follow-up in pharmacological and psychological treatment. Hierarchical regression analysis indicated that previous study treatment with CBASP or SP did not significantly predict cluster allocation, while baseline variables accounted for a large proportion of explained variance (R² _N = 0.64). Conclusion: While some patients experienced stable remission over 2 years of follow-up, the majority of patients experienced subthreshold or major depressive symptoms regardless of former study treatment with CBASP or SP. This calls for a long-term perspective implementing staging and innovative treatment approaches such as the sequential model or modular psychotherapy.

Precuneus connectivity and symptom severity in chronic depression✰

Although abnormal resting state connectivity within several brain networks has been repeatedly reported in depression, little is known about connectivity in patients with early onset chronic depression. We compared resting state connectivity in a homogenous sample of 32 unmedicated patients with early onset chronic depression and 40 healthy control participants in a seed-to-voxel-analysis. According to previous meta-analyses on resting state connectivity in depression, 12 regions implicated in default mode, limbic, frontoparietal and ventral attention networks were chosen as seeds. We also investigated associations between connectivity values and severity of depression. Patients with chronic depression exhibited stronger connectivity between precuneus and right pre-supplementary motor area than healthy control participants, possibly reflecting aberrant information processing and emotion regulation deficits in depression. Higher depression severity scores (Hamilton Rating Scale for Depression) were strongly and selectively associated with weaker connectivity between the precuneus and the subcallosal anterior cingulate. Our findings correspond to results obtained in studies including both episodic and chronic depression. This suggests that there may be no strong differences between subtypes of depression regarding the seeds analyzed here. To further clarify this issue, future studies should directly compare patients with different courses of depression.

Effects of alliance ruptures and repairs on outcomes

Objective: This study explored whether treatment outcomes in a trial on the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) vs. Supportive Psychotherapy (SP) for patients with early-onset chronic depression differ between alliance patterns. Method: Session-to-session ratings of the therapeutic alliance (Helping Alliance Questionnaire (HAQ)) from 254 outpatients with chronic depression (CBASP: 134; SP: 120) who took part in a multicenter randomized controlled trial of CBASP vs. SP were used to categorize patients into three alliance pattern categories for the patients’ and therapists’ rating separately. Based on the reliable change in the HAQ from one session to the next categories were: no rupture, unrepaired rupture, rupture-repair. Depression severity (24-item Hamilton Rating Scale for Depression) at post-treatment, at 12- and 24- months follow-up was the outcome. Results: The alliance pattern categories for therapists and patients did not differ between CBASP and SP. Only the alliance patterns calculated for patients were associated with outcome: in the unrepaired rupture category, patients had higher HRSD-ratings across time points (p = 0.047). Conclusions: CBASP was not associated with more or fewer ruptures or repairs as compared to SP in the treatment of chronic depression. The study highlights the need to resolve ruptures to avoid poor outcomes. Trial registration: ClinicalTrials.gov identifier: NCT00970437.

Two-Year Follow-Up after Treatment with the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for Early-Onset Chronic Depression

Background: Evidence on the long-term efficacy of psychotherapeutic approaches for chronic depression is scarce. Objective: To evaluate the effects of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared to Supportive Psychotherapy (SP) 1 year and 2 years after treatment termination. Methods: In this study, we present 1- and 2-year follow-up assessments of a prospective, multicenter, evaluator-blinded, randomized clinical trial of outpatients with early-onset chronic major depression (n = 268). The initial treatment included 32 sessions of CBASP or SP over 48 weeks. The primary outcome was the rate of “well weeks” (Longitudinal Interval Follow-Up Evaluation; no/minimal symptoms) after 1 year and 2 years. The secondary outcomes were, among others, clinician- and self-rated depressive symptoms, response/remission rates, and quality of life. Results: Of the 268 randomized patients, 207 (77%) participated in the follow-up. In the intention-to-treat analysis, there was no statistically significant difference between CBASP and SP patients in experiencing well weeks (CBASP: mean [SD] of 48.6 [36.9] weeks; SP: 39.0 [34.8]; rate ratio 1.26, 95% CI 0.99–1.59, p = 0.057, d = 0.18) and in remission rates (CBASP: 1 year 40%, 2 years 40.2%; SP: 1 year 28.9%, 2 years 33%) in the 2 years after treatment. Statistically significant effects were found in favor of CBASP 1 year after treatment termination regarding the rate of well weeks, self-rated depressive symptoms, and depression-related quality of life. Conclusions: CBASP lost its superiority over SP at some point between the first and the second year. This suggests the necessity of maintenance treatment for early-onset chronically depressed patients remitted with CBASP during the acute therapy phase, as well as the sequential integration of other treatment strategies, including medication for those who did not reach remission.

Effect of Disorder-Specific vs Nonspecific Psychotherapy for Chronic Depression

ImportanceChronic depression is a highly prevalent and disabling disorder. There is a recognized need to assess the value of long-term disorder-specific psychotherapy.ObjectiveTo evaluate the efficacy of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared with that of nonspecific supportive psychotherapy (SP).Design, Setting, and ParticipantsA prospective, multicenter, evaluator-blinded, randomized clinical trial was conducted among adult outpatients with early-onset chronic depression who were not taking antidepressant medication. Patients were recruited between March 5, 2010, and October 16, 2012; the last patient finished treatment on October 14, 2013. Data analysis was conducted from March 5, 2014, to October 27, 2016.InterventionsThe treatment included 24 sessions of CBASP or SP for 20 weeks in the acute phase, followed by 8 continuation sessions during the next 28 weeks.Main Outcomes and MeasuresThe primary outcome was symptom severity after 20 weeks (blinded observer ratings) as assessed by the 24-item Hamilton Rating Scale for Depression (HRSD-24). Secondary outcomes were rates of response (reduction in HRSD-24 score of ≥50% from baseline) and remission (HRSD-24 score ≤8), as well as self-assessed ratings of depression, global functioning, and quality of life.ResultsAmong 622 patients assessed for eligibility, 268 were randomized: 137 to CBASP (96 women [70.1%] and 41 men [29.9%]; mean [SD] age, 44.7 [12.1] years) and 131 to SP (81 women [61.8%] and 50 men [38.2%]; mean [SD] age, 45.2 [11.6] years). The mean (SD) baseline HRSD-24 scores of 27.15 (5.49) in the CBASP group and 27.05 (5.74) in the SP group improved to 17.19 (10.01) and 20.39 (9.65), respectively, after 20 weeks, with a significant adjusted mean difference of –2.51 (95% CI, –4.16 to –0.86; P = .003) and a Cohen d of 0.31 in favor of CBASP. After 48 weeks, the HRSD-24 mean (SD) scores were 14.00 (9.72) for CBASP and 16.49 (9.96) for SP, with an adjusted difference of –3.13 (95% CI, –5.01 to –1.25; P = .001) and a Cohen d of 0.39. Patients undergoing CBASP were more likely to reach response (48 of 124 [38.7%] vs 27 of 111 [24.3%]; adjusted odds ratio, 2.02; 95% CI, 1.09 to 3.73; P = .03) or remission (27 of 124 [21.8%] vs 14 of 111 [12.6%]; adjusted odds ratio, 3.55; 95% CI, 1.61 to 7.85; P = .002) after 20 weeks. Patients undergoing CBASP showed significant advantages in most other secondary outcomes.Conclusions and RelevanceHighly structured specific psychotherapy was moderately more effective than nonspecific therapy in outpatients with early-onset chronic depression who were not taking antidepressant medication. Adding an extended phase to acute psychotherapy seems promising in this population.Trial Registrationclinicaltrials.gov Identifier: NCT00970437.

Differentiating early-onset chronic depression from episodic depression in terms of cognitive-behavioral and emotional avoidance

BackgroundAlthough chronic depression is associated with lower global functioning and poorer treatment response than episodic depression, little is known about the differences between these two forms of depression in terms of psychological factors. Thus, the present study aimed at differentiating chronic and episodic depression regarding cognitive-behavioral and emotional avoidance that have been proposed as important risk factors for depression and promising targets for the treatment of depression. MethodsThirty patients with early onset chronic depression were compared with 30 patients with episodic depression and 30 healthy, never-depressed controls in terms of self-reported cognitive-behavioral (social and non-social) and emotional avoidance. ResultsChronically depressed patients reported more avoidance than healthy controls in each of the measures. Moreover, they reported more cognitive-nonsocial and behavioral-nonsocial as well as behavioral-social and emotional avoidance (in the form of restricted emotional expression to others) than patients with episodic depression. This kind of emotional avoidance also separated best between chronically and episodically depressed patients. Furthermore, general emotion avoidance and behavioral-social avoidance were positively correlated with levels of depression in chronically depressed patients. LimitationsThe results are based on self-report data and should thus be interpreted with caution. Additionally, the cross-sectional design limits any causal conclusions. ConclusionsThe findings underscore the relevance of cognitive-behavioral and emotional avoidance in differentiating chronic from episodic depression and healthy controls and advocate a stronger focus on maladaptive avoidance processes in the treatment of chronic depression.

Does early-onset chronic or recurrent major depression impact outcomes with antidepressant medications? A CO-MED Trial Report

Prior studies have suggested that major depressive disorder (MDD) with pre-adult onset represents a distinct subtype with greater symptom severity and higher rates of suicidal ideation. Whether these patients have poorer response to various types of antidepressant treatment than those with adult-onset MDD is unclear. Method A total of 665 psychiatric and primary care out-patients (aged 18-75 years) with non-psychotic chronic or recurrent MDD participated in a single-blind, randomized trial that compared the efficacy of escitalopram plus placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended-release plus mirtazapine. We compared participants who self-reported MDD onset (before age 18) to those with a later onset (adult onset) with respect to baseline characteristics and treatment/outcome variables at 12 and 28 weeks. Early-onset chronic/recurrent MDD was associated with a distinct set of sociodemographic (female, younger age) and clinical correlates (longer duration of illness, greater number of prior episodes, greater likelihood of atypical features, higher rates of suicidality and psychiatric co-morbidity, fewer medical problems, poorer quality of life, greater history of child abuse/neglect). However, results from unadjusted and adjusted analyses showed no significant differences in response, remission, tolerability of medications, quality of life, or retention at 12 or 28 weeks. Although early-onset chronic/recurrent MDD is associated with a more severe clinical picture, it does not seem to be useful for predicting differential treatment response to antidepressant medication. Clinicians should remain alert to an increased risk of suicidality in this population.

Comparative efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus supportive psychotherapy for early onset chronic depression: design and rationale of a multisite randomized controlled trial.

BackgroundEffective treatment strategies for chronic depression are urgently needed since it is not only a common and particularly disabling disorder, but is also considered treatment resistant by most clinicians. There are only a few studies on chronic depression indicating that traditional psycho- and pharmacological interventions are not as effective as in acute, episodic depression. Current medications are no more effective than those introduced 50 years ago whereas the only psychotherapy developed specifically for the subgroup of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), faired well in one large trial. However, CBASP has never been directly compared to a non-specific control treatment.Methods/DesignThe present article describes the study protocol of a multisite parallel-group randomized controlled trial in Germany. The purpose of the study is to estimate the efficacy of CBASP compared to supportive psychotherapy in 268 non-medicated early-onset chronically depressed outpatients. The intervention includes 20 weeks of acute treatment with 24 individual sessions followed by 28 weeks of continuation treatment with another 8 sessions. Depressive symptoms are evaluated 20 weeks after randomisation by means of the 24-item Hamilton Rating Scale of Depression (HRSD). Secondary endpoints are depressive symptoms after 12 and 48 weeks, and remission after 12, 20, and 48 weeks. Primary outcome will be analysed using analysis of covariance (ANCOVA) controlled for pre-treatment scores and site. Analyses of continuous secondary variables will be performed using linear mixed models. For remission rates, chi-squared tests and logistic regression will be applied.DiscussionThe study evaluates the comparative effects of a disorder-specific psychotherapy and a well designed non-specific psychological approach in the acute and continuation treatment phase in a large sample of early-onset chronically depressed patients.Trial registrationClinicalTrials.gov (NCT00970437).

A Method for Conducting Intensive Psychological Studies with Early-onset Chronically Depressed Patients

An intensive empirical methodology is introduced to evaluate the efficacy of Cognitive Behavioral Analysis System of Psychotherapy (CBASP) treatment for outpatients with early onset chronic depression. The patient with chronic illness presents a unique measurement challenge to psychotherapists. One of the most prominent reasons is the refractory nature of the disorder. In order to measure the change process, the authors have found it helpful to use an acquisition-learning methodology to answer three questions: (1) What are we trying to teach the patient? (2) How much has the patient learned throughout the course of therapy? And, (3) how does the extent of patient learning impact the change indices at the end of treatment and during the follow-up period? Answering questions 2 and 3 allows us to superimpose the change process variables over the performance learning variables on a graph. These combined variables also allow us to test the hypothesis: By learning what psychotherapy teaches, the chronic psychological disorder may be resolved.

Cognitive behavioral analysis system of psychotherapy versus interpersonal psychotherapy for early-onset chronic depression: A randomized pilot study

Background The only psychotherapy specifically designed and evaluated for the treatment of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), has never been directly compared to another depression-specific psychological method. Methods Thirty patients with early-onset chronic depression were randomized to 22 sessions of CBASP or Interpersonal Psychotherapy (IPT) provided in 16 weeks. Primary outcome was the score on the 24-item Hamilton Rating Scale for Depression (HRSD) assessed posttreatment by an independent blinded evaluator. Secondary endpoints were, among others, remission (HRSD ≤ 8) rates and the Beck Depression Inventory (BDI). The study included a prospective naturalistic 12-month follow-up. Results Intent-to-treat analyses of covariance (ANCOVA) revealed that there was no significant difference in posttreatment HRSD scores between the CBASP and the IPT condition, but in self-rated BDI scores. We found significantly higher remission rates in the CBASP (57%) as compared to the IPT (20%) group. One year posttreatment, no significant differences were found in the self-reported symptom level (BDI) using ANCOVA. Limitations The study used only a small sample size and no placebo control. The generalizability of the results may be limited to patients with a preference for psychological treatment. Conclusions While the primary outcome was not significant, secondary measures showed relevant benefits of CBASP over IPT. We found preliminary evidence that in early-onset chronic depression, an approach specifically designed for this patient population was superior to a method originally developed for the treatment of acute depressive episodes. Long-term results suggest that chronically depressed patients may need extended treatment courses.

Exploring preoperational features in chronic depression

Background The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) by James McCullough is the first psychotherapeutical approach specifically designed for chronic depression. Whereas its efficacy has recently been studied, empirical investigations on the underlying etiopathological hypotheses are missing. McCullough postulates that chronically depressed patients — particularly those with early onset — think preoperationally. This term was coined by J. Piaget and includes egocentrism in the views of self and others and incapacity for authentic interpersonal empathy. In accordance, empirical studies indicate a deficit in theory of mind (ToM) in depressed individuals. Methods Sixteen patients with early onset chronic depression were compared to sixteen matched healthy controls using three measurements: 1) the Movie for the Assessment of Social Cognition (MASC) as a new video-based theory of mind test, 2) self-rated questionnaires on empathy (Interpersonal Reactivity Index (IRI), and a scale assessing individual competence in relationships), and 3) a structured evaluation by the patients' therapists. Results The groups did not differ in their theory of mind performance on any aspect assessed by the used test. However, patients rated their empathy in daily life as significantly inferior to healthy controls. In addition, the therapists assigned a considerable amount of preoperational behavior to their patients. No meaningful correlations between these three types of measurements were found. Limitations: Small sample size, no structural assessment of possible psychopathology in the control group, control group was not rated by clinicians concerning preoperational behaviors. Conclusions Lack of empathy exists in the daily life of early onset chronically depressed patients according to their own and their therapists' evaluation. However, a video-based test failed to pick up deficits in their theory of mind capacities. Further research is needed to investigate theory of mind deficits using real life interpersonal interactions demanding the patient's personal involvement.

Does personality disorder decrease the likelihood of remission in early-onset chronic depression?

Background The impact of personality disorders (PD) on the course of depression has been gaining interest among clinical researchers over the past decade. Recent observational studies have found that PD was associated with impaired social functioning and reduced likelihood of depression recovery. Elevated rates of PD have been noted in early-onset and chronic forms subtypes of depression. However, scant data exist regarding the link between PD and outcome for this depression subtype. Methods The National Epidemiological Survey on Alcohol and Related Conditions database was analyzed. This survey included 43 093 respondents, 18 years and older, conducted in 2001 through 2002. Logistic regression was used to identify demographic and clinical predictors of remission in early-onset chronic depression. Results The absence of PD, having more years of education, and being married considerably improved the likelihood of remission. Paranoid personality disorder and obsessive-compulsive disorder were the only specific PD found to be associated with a reduced probability of remission. Limitations Depression remission status may have biased the recollection of PD symptoms. Borderline personality disorder, narcissistic personality disorder, and schizotypal personality disorder were not assessed. Conclusions This study suggests that PD are significant predictors of remission in early-onset chronic depression.

Cognitive Behavioral Analysis System of Psychotherapy versus Interpersonal Psychotherapy in early-onset chronic depression: A randomized, controlled pilot study with fMRI results

Cognitive Behavioral Analysis System of Psychotherapy versus Interpersonal Psychotherapy in early-onset chronic depression: A randomized, controlled pilot study with fMRI results

Age of onset in chronic major depression: relation to demographic and clinical variables, family history, and treatment response

Background: The clinical and etiological significance of the early–late onset distinction in chronic major depressive disorder was explored. Method: Subjects were 289 outpatients with DSM-III-R chronic major depression drawn from a multi-site study comparing the efficacy of sertraline and imipramine in the acute and long-term treatment of chronic depression. Patients received comprehensive evaluations using semi-structured interviews and rating scales. Results: Early-onset chronic major depression was associated with a longer index major depressive episode and higher rates of recurrent major depressive episodes, comorbid personality disorders, lifetime substance use disorders, depressive personality traits, and a history of psychiatric hospitalization. In addition, more early-onset patients tended to have a family history of mood disorders. The early-late onset distinction was not associated with differences in symptom severity, functional impairment, or treatment response. Limitations: Family members were not interviewed directly; there were a large number of statistical comparisons; and interrater reliability of the assessments was not evaluated. Conclusions: Early-onset chronic major depression has a more malignant course and is associated with greater comorbidity than late-onset chronic major depression.

One year clinical and psychosocial outcomes of early-onset chronic depression

Background: Results from short-term treatment studies have demonstrated the efficacy of antidepressant medications for outpatients with early-onset chronic depression. However, scant data exists regarding the long-term outcome of these patients treated for this disorder. Methods: The author conducted a one-year naturalistic follow-up study of 50 outpatients with early-onset, chronic depression, who were treated in a university-based psychopharmacology research clinic. Assessments were conducted blind to the patients' histories. Results: Forty-eight percent of the total sample reported 9–12 months of sustained euthymia (Months Well). Among the patients who recovered, 50% relapsed. Limitations: The major limitations of this study were its small sample size and lack of a comparison group. Conclusions: These results data demonstrate that despite initial response, many outpatients with chronic depression seem to relapse after leaving university-based psychopharmacology centers.

The efficacy of imipramine and psychotherapy in early-onset chronic depression: a reanalysis of the National Institute of Mental Health Treatment of Depression Collaborative Research Program

The authors compared the effectiveness of Cognitive Behavioral Therapy (CBT), Interpersonal Psychotherapy (IPT), Imipramine Clinical Management (ICM) to Placebo Clinical Management (PCM) for outpatients with early-onset chronic depression ( N=65) in the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program (TDRP). The post-treatment depression scores of the CBT, IPT, and ICM groups were not significantly different from the PCM group. We did not find a relationship between the duration of Major Depression and response to a specific treatment. Studies are needed to determine if combining psychotherapy with medication improves social functioning and enhances the quality of life for patients with chronic depression.

Desipramine for the treatment of "pure" dysthymia versus "double" depression

The authors report results of an 8-week, open trial of desipramine in 42 patients with DSM-III-R dysthymia with a concurrent diagnosis of major depression ("double" depression) and 33 patients with dysthymia who had no other depressive diagnosis ("pure" dysthymia). Either complete or partial remission was achieved by 70% of the patients with "pure" dysthymia. This compared favorably with but was not significantly different from results in the "double" depression group.