Distress and anhedonia as predictors of depression treatment outcome: A secondary analysis of a randomized clinical trial.
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ABSTRACT:
SUBMITTER: Khazanov GK
PROVIDER: S-EPMC6983353 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Publications
Distress and anhedonia as predictors of depression treatment outcome: A secondary analysis of a randomized clinical trial.
Khazanov Gabriela K GK Xu Colin C Dunn Barnaby D BD Cohen Zachary D ZD DeRubeis Robert J RJ Hollon Steven D SD
Behaviour research and therapy 20191031
Two core features of depression include depressed mood (heightened distress) and anhedonia (reduced pleasure). Despite their centrality to depression, studies have not examined their contribution to treatment outcomes in a randomized clinical trial providing mainstream treatments like antidepressant medications (ADM) and cognitive therapy (CT). We used baseline distress and anhedonia derived from a factor analysis of the Mood and Anxiety Symptom Questionnaire to predict remission and recovery in ...[more]
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Project description:BackgroundEarly childhood depression is associated with anhedonia and reduced event-related potential (ERP) responses to rewarding or pleasant stimuli. Whether these neural measures are indicators of target engagement or treatment outcome is not yet known.MethodsWe measured ERP responses to win and loss feedback in a guessing task and to pleasant versus neutral pictures in young (4.0-6.9 years of age) depressed children before and after randomization to either 18 weeks of Parent-Child Interaction Therapy-Emotion Development (PCIT-ED) treatment or waitlist (WL) control condition.ResultsAnalyses included reward positivity (RewP) data from 118 children randomized to PCIT-ED treatment (n = 60) or WL control condition (n = 58) at baseline and late positive potential (LPP) data from 99 children (44 PCIT-ED treatment vs. 55 WL control condition) at baseline. Children in the PCIT-ED group showed a greater reduction in anhedonia (F1,103 = 10.32, p = .002, partial η2 = .09). RewP reward responses increased more (F1,87 = 5.45, p = .02, partial η2 = .06) for PCIT-ED and a greater change in RewP was associated with a greater reduction in major depressive disorder symptoms (r = -.24, p = .05). Baseline RewP did not predict treatment change. LPPs to positive pictures did not change across treatment, but greater baseline LPPs to positive pictures predicted a higher likelihood of remission from major depressive disorder in the PCIT-ED group (B = 0.14; SE = 0.07; odds ratio = 1.15; p = .03).ConclusionsThe ERP reward response improved in young children with depression during a treatment designed to enhance emotion development, providing evidence of target engagement of the neural systems associated with reward. Further, greater baseline LPP responses to positive pictures were associated with a greater reduction in depression, suggesting that this ERP measure can predict which children are most likely to respond to treatment.
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Project description:ObjectiveThe current study examined predictors and moderators of two interventions for binge-eating disorder (BED).MethodParticipants were 112 adults with BED (Mage = 39.7 ± 13.4 years; MBMI = 35.1 ± 13.4 kg/m²; 82% female; 91% Caucasian) randomly assigned to integrative cognitive-affective therapy for BED (ICAT-BED) or guided self-help cognitive-behavioral therapy (CBTgsh). Generalized linear models examined predictors and moderators of objective binge-eating episode (OBE) frequency and OBE abstinence at end-of-treatment (EOT) and 6-month follow-up (FU).ResultsLower levels of baseline dietary restraint and emotion regulation difficulties predicted greater reductions in OBE frequency at EOT and FU, respectively. At EOT, greater pretreatment self-control predicted greater reductions in OBE frequency in ICAT-BED than CBTgsh (ps < .05). In addition, low shape/weight overvaluation predicted greater reductions in OBE frequency in ICAT-BED than CBTgsh, whereas high shape/weight overvaluation predicted comparable reductions in OBE frequency across treatments at EOT (ps < .02). At EOT and FU, greater baseline actual-ideal self-discrepancy predicted significantly greater reductions in OBE frequency in ICAT-BED, than CBTgsh (ps < .02). No significant predictor or moderator effects were observed for models examining OBE abstinence.ConclusionThis study identified two general predictors and four moderators of BED treatment response. However, only one predictor (actual-ideal self-discrepancy) interacted with treatment type to differentially predict OBE frequencies at both EOT and FU. Altogether, findings suggest that ICAT-BED may confer specific and durable improvements in OBE frequencies among individuals with high actual-ideal self-discrepancy. Therefore, patients demonstrating these characteristics may be more likely to benefit from ICAT-BED. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Project description:ImportanceThe ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD.ObjectiveTo evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT.Design, setting, and participantsThis secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians.ExposuresEligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks.Main outcomes and measuresAssociation between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses.ResultsAmong the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment.Conclusions and relevanceIn this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.
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Project description:ImportanceThe application of precision medicine principles for the treatment of depressive disorders in adolescents requires an examination of the variables associated with depression outcomes in randomized clinical trials (RCTs).ObjectiveTo describe predictors, moderators, and mediators associated with outcomes in RCTs for the treatment of depressive disorders in adolescents.Evidence reviewA scoping review of RCTs for the treatment of depression in adolescents was conducted. Databases searched included MEDLINE, Embase, APA PsycInfo, and CINAHL. Included publications tested predictors, moderators, and/or mediators associated with depression symptom outcomes (eg, symptom reduction, response, remission) in RCTs pertaining to the treatment of adolescents, ages 13 to 17 years. Predictors were defined as variables that were associated with depression outcomes, independent of treatment group. Moderators were defined as baseline variables that were associated with differential outcomes between treatment groups. Mediators were defined by a formal mediation analysis. In duplicate, variables were extracted and coded with respect to analysis type (univariable or multivariable), statistical significance, direction of effect size, reporting of a priori hypotheses, and adjustment for multiple comparisons. Aggregated results were summarized by variable domain and RCT sample.FindingsEighty-one articles reporting on variables associated with outcomes across 33 RCTs were identified, including studies of biological (10 RCTs), psychosocial (18 RCTs), and combined (4 RCTs) treatments as well as a service delivery model (1 RCT). Fifty-three variable domains were tested as baseline predictors of depression outcome, 41 as moderators, 19 as postbaseline predictors, and 5 as mediators. Variable domains that were reported as significant in at least 3 RCTs included age, sex/gender, baseline depression severity, early response to treatment, sleep changes, parent-child conflict, overall psychopathology, suicidal ideation, hopelessness, functional impairment, attendance at therapy sessions, and history of trauma. Two publications reported a priori hypotheses and adjustment for multiple comparisons, both finding that baseline depression severity and family conflict were associated with poorer outcomes.Conclusions and relevanceThis review identified commonly researched variables requiring more scrutiny as well as underresearched variables to inform future study designs. Further efforts to discover predictors, moderators, and mediators associated with treatment response have great potential to optimize care for adolescents with depression.
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Project description:BackgroundMajor depressive disorder (MDD) is often comorbid with metabolic diseases such as obesity, cardiovascular disease, and type 2 diabetes. A potential link between these disorders is adiponectin, an adipocyte-derived circulating hormone with insulin-sensitizing, anti-inflammatory, and neuroplasticity effects. Reductions in plasma levels of adiponectin have been reported in both humans with depression and in the chronic-defeat mouse model of depression. However, the predictive value of adiponectin for treatment response to depression has not been determined.MethodsWe investigated the potential predictive effect of baseline adiponectin levels in patients who provided plasma and were undergoing one of three pharmacological treatments (escitalopram monotherapy; escitalopram plus bupropion; and venlafaxine plus mirtazapine) in the Combining Medications to Enhance Depression Outcomes clinical trial (n=160). Specifically, we assessed whether adiponectin moderates-that is, differentially predicts-treatment response among the treatment arms. Improvements with treatment were assessed using change in the clinician-rated 30-item Inventory of Depressive Symptomatology (IDS-C) from baseline through week 12. Moderator effects were tested using separate pairwise repeated measures mixed-effects models with a treatment-arm-by-adiponectin interaction.ResultsBaseline adiponectin levels moderated treatment outcome between two combination therapies. Specifically, low adiponectin predicted better response to escitalopram plus bupropion compared to venlafaxine plus mirtazapine, whereas high adiponectin predicted better response to venlafaxine plus mirtazapine compared to escitalopram plus bupropion (F=4.84, p=0.03). Adiponectin levels did not correlate with baseline depression severity (r=-0.03, p=.59).ConclusionsAntidepressant selection for patients with MDD can be personalized using pre-treatment blood-based biomarkers, such as adiponectin, thereby improving treatment outcomes.
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| S-EPMC8491723 | biostudies-literature
Project description:ObjectiveThis study examined predictors and moderators of outcome in 2 treatments for bulimia nervosa (BN).MethodEighty adults with BN symptoms at 1 of 2 sites were randomized to 21 sessions of integrative cognitive-affective therapy for BN (ICAT-BN) or enhanced cognitive behavior therapy (CBT-E). Generalized linear models examined predictors and moderators of improvements in bulimic behavior and eating disorder psychopathology at end of treatment (EOT) and 4-month follow-up (FU).ResultsAt EOT, individuals with higher dietary restraint had greater reductions in bulimic behavior. At FU, individuals with higher weight and shape concern had greater reductions in bulimic behavior, whereas those with greater baseline depression had less improvement in eating disorder psychopathology. Individuals higher in stimulus seeking had greater reductions in bulimic behavior and eating disorder psychopathology at follow up in ICAT-BN than in CBT-E, whereas individuals lower in stimulus seeking had greater reductions in bulimic behavior in CBT-E than in ICAT-BN. Finally, individuals with higher affective lability had greater reductions in eating disorder psychopathology in ICAT-BN than in CBT-E, whereas improvements were comparable across treatments for individuals with lower affective lability.ConclusionsThis study identified 3 nonspecific predictors of outcome (i.e., dietary restraint, weight and shape concern, and depression) and 2 moderators (i.e., affective lability and stimulus seeking). All moderator effects emerged at FU rather than at EOT, suggesting that the moderating effects of treatment were not immediately apparent. These results suggest that individuals with higher affective lability and stimulus seeking may benefit more from treatment with a greater focus on affective states and self-regulation.
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Project description:BACKGROUND: Minor depression is almost twice as common in primary care (PC) as major depression. Despite the high prevalence, few evidence-based algorithms exist for managing patients with minor depression or patients presenting solely with distress. OBJECTIVES: The aim of this study was to test the effectiveness of a telephone-based close monitoring program to manage PC patients with minor depression or distress. DESIGN: Subjects were randomly assigned to either the control arm (usual care; UC) or the intervention arm (close monitoring; CM). We hypothesized that those randomized to CM would exhibit less depression and be less likely to have symptoms progress to the point of meeting diagnostic criteria. SUBJECTS: Overall, 223 PC subjects with minor depression or distress consented to participation in this trial. MEASUREMENTS: At baseline, subjects completed a telephone-based evaluation comprised of validated diagnostic assessments of depression and other MH disorders. Outcomes were assessed at six months utilizing this same battery. Chart reviews were conducted to track care received, such as prescribed antidepressants and MH and primary care visits. RESULTS: Subjects in the CM arm exhibited fewer psychiatric diagnoses than those in the UC arm (chi(2) = 4.04, 1 df, p = 0.04). In addition, the intervention group showed improved overall physical health (SF-12 PCS scores) (M = 45.1, SD = 11.8 versus M = 41.5, SD = 12.4) (chi(2) = 5.90, 1 df, p = .02). CONCLUSIONS: Those randomized to CM exhibited less MH problems at the conclusion of the trial, indicating that the close monitoring program is effective, feasible and valuable. The findings of this study will allow us to enhance clinical care and support the integration of mental health services and primary care.
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Project description:Importance:Nonadherence to antidepressant medication is common and leads to poor outcomes. Early nonadherence is especially problematic. Objective:To test the effectiveness of a psychosocial intervention to improve early adherence among older patients whose primary care physician newly initiated an antidepressant for depression. Design, Setting, and Participants:The Treatment Initiation and Participation Program (TIP) was offered in a 2-site randomized clinical effectiveness study between January 2011 and December 2014 at primary care practices in New York, New York, and Ann Arbor, Michigan. Analyses began in February 2016. All participants were middle-aged and older adults (aged ?55 years) who received newly initiated depression treatment by their primary care physician and recruited within 10 days of their prescription. Analyses were intention-to-treat. Interventions:Participants were randomly assigned to the intervention (TIP) or treatment as usual. Participants in the TIP group identified and addressed barriers to adherence, including stigma, misconceptions, and fears about treatment, before developing a personalized adherence strategy. The Treatment Initiation and Participation Program was delivered in three 30-minute contacts scheduled during a 6-week period just after the antidepressant was prescribed. Main Outcomes and Measures:The primary outcome was self-reported adherence on the Brief Medication Questionnaire, with adequate early adherence defined as taking 80% or more of the prescribed doses at 6 and 12 weeks. The secondary outcome was depression severity. Results:In total, 231 middle-aged and older adults (167 women [72.3%] and 64 men [27.7%]) without significant cognitive impairment were randomly assigned to the TIP intervention (n?=?115) or treatment as usual (n?=?116). Participants had a mean (SD) age of 67.3 (8.4) years. Participants in the TIP group were 5 times more likely to be adherent at 6 weeks (odds ratio,?5.54; 95% CI, 2.57 to 11.96; ?21?=?19.05; P?<?.001) and 3 times more likely to be adherent at both 6 and 12 weeks (odds ratio,?3.27; 95% CI, 1.73 to 6.17; ?21?=?13.34; P?<?.001). Participants in the TIP group showed a significant earlier reduction (24.9%) in depressive symptoms (95% CI, 13.9 to 35.9; t337?=?4.46; adjusted P?<?.001). In both groups, participants who were 80% adherent at weeks 6 and 12 had a 15% greater improvement in depressive symptoms from baseline over the course of treatment (95% CI, -0.2 to -30; t369?=?1.93; P?=?.051). Conclusions and Relevance:The Treatment Initiation and Participation Program is an effective intervention to improve early adherence to pharmacotherapy. Improved adherence can promote improvement in depression. Trial Registration:clinicaltrials.gov Identifier: NCT01301859.
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Project description:BackgroundMultiple studies have attempted to increase the rate of intravenous thrombolysis for ischemic stroke using interventions to promote adherence to guidelines. Still, many of them did not measure individual-level impact. This study aimed to make a posthoc comparison of the clinical outcomes of patients in the "Thrombolysis ImPlementation in Stroke (TIPS)" study, which aimed to improve rates of intravenous thrombolysis in Australia.MethodsA posthoc analysis was conducted using individual-level patient data. Excellent (Three-month post treatment modified Rankin Score 0-2) and poor clinical outcome (Three-month post treatment modified Rankin Score 5-6) and post treatment parenchymal haematoma were the three main outcomes, and a mixed logistic regression model was used to assess the difference between the intervention and control groups.ResultsThere was a non-significant higher odds of having an excellent clinical outcome of 57% (odds ratio: 1.57; 95% CI: 0.73-3.39) and 33% (odds ratio: 1.33; 95% CI: 0.73-2.44) during the active-and post-intervention period respectively, for the intervention compared to the control group. A non-significant lower odds of having a poor clinical outcome was also found in the intervention, relative to control group of 4% (odds ratio: 0.96; 95% CI: 0.56-2.07) and higher odds of having poor outcome of 44% (odds ratio: 1.44 95% CI: 0.61-3.41) during both active and post-intervention period respectively. Similarly, a non-significant lower odds of parenchymal haematoma was also found for the intervention group during the both active- (odds ratio: 0.53; 95% CI: 0.21-1.32) and post-intervention period (odds ratio: 0.96; 95% CI: 0.36-2.52).ConclusionThe TIPS multi-component implementation approach was not effective in reducing the odds of post-treatment severe disability at 90 days, or post-thrombolysis hemorrhage.Trial registrationClinical Trial Registration-URL: http://www.anzctr.org.au/ Unique Identifier: ACTRN12613000939796 .
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