Treatment Of Persistent Depressive Disorder Research Articles

A randomized controlled trial of desvenlafaxine-induced structural brain changes in the treatment of persistent depressive disorder

The anatomical changes that antidepressant medications induce in the brain and through which they exert their therapeutic effects remain largely unknown. We randomized 61 patients with Persistent Depressive Disorder (PDD) to receive either desvenlafaxine or placebo in a 12-week trial and acquired anatomical MRI scans in 42 of those patients at baseline before randomization and immediately at the end of the trial. We also acquired MRIs once in 39 age- and sex-matched healthy controls. We assessed whether the serotonin-norepinephrine reuptake inhibitor, desvenlafaxine, differentially changed cortical thickness during the trial compared with placebo. Patients relative to controls at baseline had thinner cortices across the brain. Although baseline thickness was not associated with symptom severity, thicker baseline cortices predicted greater reduction in symptom severity in those treated with desvenlafaxine but not placebo. We did not detect significant treatment-by-time effects on cortical thickness. These findings suggest that baseline thickness may serve as predictive biomarkers for treatment response to desvenlafaxine. The absence of treatment-by-time effects may be attributable either to use of insufficient desvenlafaxine dosing, a lack of desvenlafaxine efficacy in treating PDD, or the short trial duration.

Suicidal behaviors are associated with loneliness and decrease during inpatient CBASP treatment for persistent depressive disorder

Suicidal ideation and behavior (SIB) are common in persistent depressive disorder (PDD) and may be related to interpersonal dysfunction. While SIB has been extensively analyzed in other high-risk disorders (e.g., borderline personality disorder, BPD), data on interpersonal risk factors and effects of specific psychotherapy on SIB in PDD are limited. This study aimed at investigating loneliness versus social network size as interpersonal risk factors for SIB in PDD and assess effects of cognitive behavioral analysis system of psychotherapy (CBASP) on this domain. In a prospective naturalistic study, 64 PDD patients were assessed, who underwent a 10-weeks inpatient CBASP program. Our clinical comparison group consisted of 34 BPD patients, who underwent a 10-weeks inpatient dialectical behavioral therapy (DBT) program. SIB was measured with the Columbia-Suicide Severity Rating Scale (C-SSRS), loneliness and social network size with the UCLA Loneliness Scale (UCLA) and the Social Network Index (SNI). Twenty-six PDD patients (40.6% of the PDD sample) showed current SIB at baseline in comparison with 26 BPD patients (76.5% of the BPD sample). While in suicidal PDD patients, SIB was associated with perceived social isolation (UCLA), but not with reduced social network size (SNI), this association was not observed in suicidal BPD patients. In PDD, SIB significantly decreased during CBASP. In conclusion, SIB appears to be associated with interpersonal factors related to loneliness in PDD, but not in BPD. CBASP showed first positive evidence in reducing SIB in PDD, but our pilot data need replication studies.

Serotonin-norepinephrine reuptake inhibitor antidepressant effects on regional connectivity of the thalamus in persistent depressive disorder: evidence from two randomized, double-blind, placebo-controlled clinical trials.

Previous neuroimaging studies have shown that serotonin–norepinephrine reuptake inhibitor antidepressants alter functional activity in large expanses of brain regions. However, it is not clear how these regions are systemically organized on a connectome level with specific topological properties, which may be crucial to revealing neural mechanisms underlying serotonin–norepinephrine reuptake inhibitor treatment of persistent depressive disorder. To investigate the effect of serotonin–norepinephrine reuptake inhibitor antidepressants on brain functional connectome reconfiguration in persistent depressive disorder and whether this reconfiguration promotes the improvement of clinical symptoms, we combined resting-state functional magnetic resonance imaging (fMRI) scans acquired in two randomized, double-blind, placebo-controlled trial studies of serotonin–norepinephrine reuptake inhibitor antidepressant treatment of patients with persistent depressive disorder. One was a randomized, double-blind, placebo-controlled trial of 10-week duloxetine medication treatment, which included 17 patients in duloxetine group and 17 patients in placebo group (ClinicalTrials.gov Identifier: NCT00360724); the other one was a randomized, double-blind, placebo-controlled trial of 12-week desvenlafaxine medication treatment, which included 16 patients in desvenlafaxine group and 15 patients in placebo group (ClinicalTrials.gov Identifier: NCT01537068). The 24-item Hamilton Depression Rating Scale was used to measure clinical symptoms, and graph theory was employed to examine serotonin–norepinephrine reuptake inhibitor antidepressant treatment effects on the topological properties of whole-brain functional connectome of patients with persistent depressive disorder. We adopted a hierarchical strategy to examine the topological property changes caused by serotonin–norepinephrine reuptake inhibitor antidepressant treatment, calculated their small-worldness, global integration, local segregation and nodal clustering coefficient in turn. Linear regression analysis was used to test associations of treatment, graph properties changes and clinical symptom response. Symptom scores were more significantly reduced after antidepressant than placebo administration (η2 = 0.18). There was a treatment-by-time effect that optimized the functional connectome in a small-world manner, with increased global integration and increased nodal clustering coefficient in the bilateral thalamus (left thalamus η2 = 0.21; right thalamus η2 = 0.23). The nodal clustering coefficient increment of the right thalamus (ratio = 29.86; 95% confidence interval, −4.007 to −0.207) partially mediated the relationship between treatment and symptom improvement, and symptom improvement partially mediated (ratio = 21.21; 95% confidence interval, 0.0243–0.444) the relationship between treatment and nodal clustering coefficient increments of the right thalamus. Our study may indicate a putative mutually reinforcing association between nodal clustering coefficient increment of the right thalamus and symptom improvement from serotonin–norepinephrine reuptake inhibitor antidepressant treatments with duloxetine or desvenlafaxine.

Borderline Personality Features in Patients With Persistent Depressive Disorder and Their Effect on CBASP Outcome.

Introduction: The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) was developed for the treatment of persistent depressive disorder (PDD), where comorbid personality disorders (PD) are common. In contrast to other PD, comorbid borderline personality disorder (BPD) is often regarded as an exclusion criterion for CBASP. In clinical settings, however, subthreshold BPD symptoms are prevalent in PDD and may not be obvious at an initial assessment prior to therapy. As data on their impact on CBASP outcome are very limited, this naturalistic study investigates BPD features in PDD and their relevance for the therapeutic outcome of a multimodal CBASP inpatient program.Method: Sixty patients (37 female, mean age 38.3, SD 11.9 years) meeting DSM-5 criteria for PDD underwent a 10 weeks CBASP inpatient program. BPD features (i.e., number of fulfilled DSM-5 criteria) together with childhood maltreatment and rejection sensitivity were assessed on admission. Before and after treatment, severity of depressive symptoms was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI-II). BPD symptoms were assessed using the Borderline Personality Disorder Severity Index (BPDSI-IV) and the Borderline Symptom List (BSL-23). Intercorrelations of baseline characteristics and symptom change during treatment were analyzed.Results: Patients with PDD met a mean of 1.5 (SD 1.6) BPD criteria with 4 patients fulfilling ≥5 criteria. BPD symptoms and depressive symptoms showed a strong correlation, and BPD symptoms were additionally correlated with emotional abuse and rejection sensitivity. There was no association between BPD features at baseline and improvement on the MADRS, however, BPD features tended to be associated with a lower response according to the BDI-II score after 10 weeks of treatment. Furthermore, BPD symptoms (i.e., abandonment, impulsivity and affective instability) were reduced after 10 weeks of CBASP treatment.Discussion: BPD symptoms are prevalent in patients with PDD and highly intertwined with the experience of depressive symptoms. In this naturalistic study in PDD, BPD features at baseline did not limit the clinical response to CBASP. Future studies may extend the spectrum of PDD to comorbid subsyndromal or even syndromal BPD in order to develop tailored psychotherapeutic treatment for these complex affective disorders.

Gray matter reorganization underpinnings of antidepressant treatment of persistent depressive disorder

Brain gray matter is organized in a manner with interconnected brain regions, resulting in a notable covariance pattern that recapitulates either the functional coactivation or structural connectivity of brain regions, which is believed to underpin psychiatric disorders such as depression. This study aimed to investigate whether and how antidepressants took effect in treating depression and reducing symptoms by altering the gray matter covariance pattern. We combined structural magnetic resonance imaging (MRI) scans acquired in two randomized, double-blind, placebo-controlled trial (RCT) studies of the treatment using serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant medications in patients with persistent depressive disorder (PDD). One was an RCT of 10-week duloxetine medication that consisted of patients who received duloxetine (N = 21) or placebo (N = 21), and the other was an RCT of 12-week desvenlafaxine medication that consisted of 19 and 17 patients respectively who received desvenlafaxine or placebo. We examined treatment effect on gray matter volume (GMV) and topological organization of GMV covariance pattern (i.e., GMV-based network). We found a treatment-by-time effect on GMV in the angular gyrus and cuneus areas, whereas the GMV change rate of the cuneus was inversely correlated with the response rate. We observed a significant increase in the local efficiency of the GMV-based network following medication treatment compared with placebo. Our findings provide preliminary evidence for a GMV-based network-specific reconfiguration caused by antidepressants compared to placebo and the cuneus may be a possible candidate region to predict antidepressant response.

Impact of Baseline Characteristics on the Effectiveness of Disorder-Specific Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and Supportive Psychotherapy in Outpatient Treatment for Persistent Depressive Disorder.

Importance: In the treatment of persistent depressive disorder (PDD), disorder-specific Cognitive Behavioral Analysis System of Psychotherapy (CBASP) has been shown to be superior to Supportive Psychotherapy (SP) in outpatients. It remains to clear which subgroups of patients benefit equally and differentially from both psychotherapies.Objective: To identify those patient-level baseline characteristics that predict a comparable treatment effectiveness of CBASP and SP and those that moderate the differential effectiveness of CBASP compared to SP.Design, setting and participants: In this analysis of a 48-week multicenter randomized clinical trial comparing CBASP to SP in adult antidepressant-free outpatients with early-onset PDD, we evaluated baseline variables from the following domains as potential predictors and moderators of treatment effectiveness: socio-demography, clinical status, psychosocial and global functioning, life quality, interpersonal problems, childhood trauma, treatment history, preference for psychotherapy, and treatment expectancy.Interventions: A 48-week treatment program with 32 sessions of either CBASP or SP.Main outcomes and measures: Depression severity measured by the 24-item Hamilton Rating Scale for Depression (HRSD-24) at week 48.Results: From N = 268 randomized outpatients, N = 209 completed the 48-week treatment program. CBASP completers had significantly lower post-treatment HRSD-24 scores than SP completers (meanCBASP=13.96, sdCBASP= 9.56; meanSP= 16.69, sdSP= 9.87; p = 0.04). A poor response to both therapies was predicted by higher baseline levels of clinician-rated depression, elevated suicidality, comorbid anxiety, lower social functioning, higher social inhibition, moderate-to-severe early emotional or sexual abuse, no preference for psychotherapy, and the history of at least one previous inpatient treatment. Moderator analyses revealed that patients with higher baseline levels of self-rated depression, comorbidity of at least one Axis-I disorder, self-reported moderate-to-severe early emotional or physical neglect, or at least one previous antidepressant treatment, had a significantly lower post-treatment depression severity with CBASP compared to SP (all p < 0.05).Conclusions and relevance: A complex multifactorial interaction between severe symptoms of depression, suicidality, and traumatic childhood experiences characterized by abuse, social inhibition, and anxiety may represent the basis of non-response to psychotherapy in patients with early onset PDD. Specific psychotherapy with CBASP might, however, be more effective and recommendable for a variety of particularly burdened patients compared to SP.

Group Cognitive Behavioral Analysis System of Psychotherapy (CBASP): A Pilot Study for Bipolar Depression.

ObjectivesCognitive Behavioral Analysis System of Psychotherapy (CBASP) is an individually administered treatment model designed specifically for Persistent Depression however bipolar patients have traditionally been excluded from CBASP studies. There is a perception that bipolar depression will be harder to treat and requires a unique psychological approach. This pilot study reports on the feasibility of administering the same 20-week manualized group CBASP therapy with bipolar patients currently in a depressive episode.MethodsThis non-randomized, single-arm prospective pilot study, reports on an a posteriori exploration of benefits to bipolar depressed patients (n=26) of the same 20-week group CBASP intervention administered to unipolar depressed patients (n=81). The clinical trial for the initial phase examining benefits of the manualized 20-week group CBASP intervention with unipolar patients was registered with the ISRCTN registry, study ID: ISRCTN95149444. Results reported here include mixed ANOVA analyses, across group treatment models and diagnostic categories. Changes over time in self-reported depressive symptoms (Inventory of Depressive Symptoms -IDS-SR), self-reported social functioning, interpersonal problems and interpersonal dispositions are documented for all patients. An exploratory longitudinal latent class analysis was used to examine patients’ trajectories of improvement in depressive symptoms. Finally, the best predictors of change in reported depressive symptoms were explored with a logistic regression for all patients. ResultsImprovements in depressive symptoms and in social functioning over time were significant for all patients with bipolar patients trending towards a greater improvement in depressive symptoms after controlling for baseline differences. An exploratory Latent Class Analysis identified two different treatment trajectories for the entire sample: 1) moderate to severely depressed patients who improved significantly (49%) and 2) severely depressed patients who did not improve (51%). The best predictors of non-response to group therapy include high baseline problems in social functioning and low rates of self-reported Perceived Improvements in overall health. ConclusionBipolar patients in a depressive episode appear to benefit from the same 20-week group CBASP model designed originally for the treatment of Persistent Depressive Disorder. Bipolar patients seem more easily mobilized both during and outside of group therapy sessions and report more interpersonal confidence and more agency than unipolar depressed patients.

Group Cognitive Behavioural Analysis System of Psychotherapy (CBASP) for persistently depressed outpatients: a retrospective chart review.

BackgroundCognitive behavioural analysis system of psychotherapy (CBASP) is an effective individual treatment for persistent depressive disorder (PDD), but evidence on group treatment (Group‐CBASP) is limited. Our aim was to review the effect of Group‐CBASP on self‐report depression severity in outpatients with PDD, overall and by age of depression‐onset.MethodsA retrospective chart review study (November 2011–March 2017) in 54 patients with PDD (29 late‐onset, 25 early‐onset). Patients were previously treated by pharmacotherapy (92.6%), psychotherapy (98.1%) and/or electroconvulsive therapy (11.1%). Group‐CBASP involved 24 weekly sessions during 6 months, followed by individual appointments over 6 months. The Inventory of Depressive Symptoms ‐self rating(IDS‐SR) was used at baseline and after 3, 6, 9 and 12 months, computing mean differences and response rates.ResultsThe mean IDS‐SR score decreased significantly from 39.83 at baseline to 33.78 at 6 months: a decrease from severe to moderate depression after 24 weeks of Group‐CBASP, with a medium effect size (Cohen’s d = .49). At 12 months, the mean IDS‐SR score was 32.81, indicating moderate symptom levels remained. At 6 and 12 months, mean IDS‐SR scores were similar among late‐ versus early‐onset patients, but at 12 months response rates were higher among late‐onset patients.LimitationsAlthough results of our study provide valuable input for future prospective studies, limitations were the use of a retrospective design and the small group size.ConclusionGroup‐CBASP offered to an outpatient population with PDD was associated with clinically relevant decrease in self‐reported symptom severity, and with sustained response particularly in patients with late onset of depression.Practitioner points Group‐CBASP seems to be a good alternative for CBASP in individual setting.Patients with late age of depression‐onset seem to benefit more from Group‐CBASP.This study shows that clinical relevant effects of Group‐CBASP, followed by individual contacts, remain at least for 6 months.Research on personalizing treatment strategies is needed to improve patient assignment for Group‐CBASP.

How is a specialist depression service effective for persistent moderate to severe depressive disorder?: a qualitative study of service user experience

BackgroundA specialist depression service (SDS) offering collaborative pharmacological and cognitive behaviour therapy treatment for persistent depressive disorder showed effectiveness against depression symptoms versus usual community based multidisciplinary care in a randomised controlled trial (RCT) in specialist mental health services in England. However, there is uncertainty concerning how specialist depression services effect such change. The current study aimed to evaluate the factors which may explain the greater effectiveness of SDS compared to Treatment as Usual (TAU) by exploring the experience of the RCT participants.MethodsQualitative audiotaped and transcribed semi-structured interviews were conducted 12–18 months after baseline with 21 service users (12 SDS, 9 TAU arms) drawn from all three sites. Inductive thematic analysis using a grounded approach contrasted the experiences of SDS with TAU participants.ResultsFour themes emerged in relation to service user experience: 1. Specific treatment components of the SDS: which included sub-themes of the management of medication change, explaining and developing treatment strategies, setting realistic expectations, and person-centred and holistic approach; 2. Individual qualities of SDS clinicians; 3. Collaborative team context in SDS: which included sub-themes of communication between healthcare professionals, and continuity of team members; 4. Accessibility to SDS: which included sub-themes of flexibility of locations, frequent consultation as reinforcement, gradual pace of treatment, and challenges of returning to usual care.ConclusionsThe study uncovered important mechanisms and contextual factors in the SDS that service users experience as different from TAU, and which may explain the greater effectiveness of the SDS: the technical expertise of the healthcare professionals, personal qualities of clinicians, teamwork, gradual pace of care, accessibility and managing service transitions. Usual care in other specialist mental health services may share many of the features from the SDS.Trial registration“Trial of the Clinical and Cost Effectiveness of a Specialist Expert Mood Disorder Team for Refractory Unipolar Depressive Disorder” was registered in www.ClinicalTrials.gov (NCT01047124) on 12–01-2010 and the ISRCTN registry was registered in www.isrctn.com (ISRCTN10963342) on 25–11-2015 (retrospectively registered).

Do social functioning and symptoms improve with continuation antidepressant treatment of persistent depressive disorder? An observational study

ObjectiveTo determine efficacy of continued treatment with the serotonin norepinephrine reuptake inhibitor duloxetine on symptom reduction and functional improvement in outpatients with dysthymia. MethodFifty outpatients with DSM-IV-TR diagnosed dysthymia who had participated in a 10 week double-blind, placebo-controlled study of duloxetine received open treatment for three months. Nineteen duloxetine responders continued duloxetine, 24 patients initially treated with placebo started open duloxetine treatment, and 7 duloxetine non-responders were treated with desvenlafaxine or bupropion, selected by clinician choice. ResultsPatients continuing duloxetine maintained symptom improvement, 84% meeting response and 63% remission criteria at week 22. Patients initially treated with placebo showed similarly high levels of response (83%) and remission (62%) at week 22, and most duloxetine non-responders subsequently responded to other antidepressants. Duloxetine-continuation patients improved modestly between weeks 10 and 22 on measures of social and cognitive functioning and temperament. Despite this improvement concurrently across several functional domains, 66.7% of patients continuing duloxetine remained in the impaired range of functioning according to the Social Adjustment Scale (SAS). ConclusionsContinued duloxetine treatment appears to be effective in maintaining symptom response in dysthymic disorder, and has positive effects on social functioning. However, the majority of patients do not show normalization of functioning, even when controlling for remission status. Additional treatments should be considered to target residual impairments in social functioning in mood remitted patients with persistent depressive disorder.