Objective
Reanalyse the patient-level data set of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study with fidelity to the original research protocol and related publications.
Design
The study was open label and semirandomised examining the effectiveness of up to four optimised and increasingly aggressive, antidepressant therapies in depressed adults. Patients who failed to gain adequate relief from their level 1 trial on the SSRI citalopram could receive up to three additional treatment trials in levels 2–4.
Setting
41 North American psychiatry and primary care treatment centres.
Participants
4041 adults screened positive for major depressive disorder. In contrast to most clinical trials, STAR*D enrolled patients seeking care (vs recruited) and included patients with a wide range of common comorbid medical and psychiatric conditions to enhance the generalisability of findings to real-world clinical practice.
Interventions
STAR*D evaluated the relative effectiveness of 13 antidepressants therapies in treatment levels 2–4 for depressed patients who failed to gain adequate benefit from their level 1 medication trial.
Main outcome measures
According to the STAR*D protocol, the primary outcome was remission, defined as a score <8 on the blinded Hamilton Rating Scale for Depression (HRSD). Response was a secondary outcome defined as ≥50% reduction in HRSD scores. STAR*D’s protocol specifically excluded all non-blinded clinic-administered assessments from use as research outcome measures.
Results
STAR*D investigators did not use the protocol-stipulated HRSD to report cumulative remission and response rates in their summary article and instead used a non-blinded clinic-administered assessment. This inflated their report of outcomes, as did their inclusion of 99 patients who scored as remitted on the HRSD at study outset as well as 125 who scored as remitted when initiating their next-level treatment. These patients should have been excluded from data analysis. In contrast to the STAR*D-reported 67% cumulative remission rate after up to four antidepressant treatment trials, the rate was 35.0% when using the protocol-stipulated HRSD and inclusion in data analysis criteria.
Conclusion
STAR*D’s cumulative remission rate was approximately half of that reported.
University of Idaho - Research Portal
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VERSO (Vandal Expertise, Research, and Scholarship Online) preserves and provides access to the research and creative output of the University of Idaho's faculty, students and staff.
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Top Ten
Journal article
by H Edmund Pigott, Thomas Kim, Colin Xu, Irving Kirsch and Jay Amsterdam
Journal article
by Thomas Kim, Colin Xu and Jay D. Amsterdam
Objectives: Antidepressants may be less effective in treatment-resistant depression (TRD). In this exploratory study, we examined the widely held hypothesis that monoamine oxidase inhibitor (MAOI) therapy may be superior to tricyclic antidepressant (TCA) therapy for TRD. We also examined the influence of the number of prior treatment trials on TCA versus MAOI effectiveness in TRD.
Methods: Data were retrospectively extracted from approximately 2,500 treatment charts of patients with TRD who were attending a university mood disorder clinic between 1983 and 2015. Hierarchical linear modeling was used to examine the efficacy of drug class on outcome as well as the interaction between drug class and the number of prior antidepressant trials.
Results: 147 treatment outcome observations were made from 94 unipolar, depressed patients who either received TCA (N = 47) or MAOI (N = 100) monotherapy for TRD. For patients unresponsive to at least one prior trial, drug class significantly predicted end-of-treatment CGI/S scores, with TCAs showing worse (i.e., higher) end-of-treatment CGI/S scores relative to MAOI therapy (b = 1.04, t = 4.98, p < 0.0001). When examining the interaction between drug class and the number of prior antidepressant trials, the interaction effect was significant (b = -0.50, t = -2.43, p = 0.02); however, the advantage for MAOI versus TCA therapy decreases with more prior, failed, antidepressant trials.
Conclusion: Results suggest that MAOIs may be more effective than TCAs for early stage TRD. This difference in effectiveness between MAOIs and TCAs diminished as the number of prior treatment trials increased. However, the TCA sample size was limited and the analysis was retrospective with non-randomized conditions.
Journal article
by Thomas T. Kim, Colin Xu and Robert J. Derubeis
Objective: An implicit assumption in the use of depressive severity measures to assess change during treatment, such as the Hamilton Rating Scale for Depression (HRSD), is that reductions from pre- to post-treatment that are equal to each other are of equal value. However, stakeholders' valuations of changes might depart substantially from this assumption. Method: Vignettes were constructed that reflected the six possible 1, 2, and 3-point reductions on five cognitive and four somatic symptoms derived from the HRSD. Former or currently depressed patients provided judgments of the importance of the symptom reductions. Mean importance ratings were modeled using symptom category and the pre/post-treatment combination. Differences were explored using the Tukey method. Results: Results indicated that mean ratings, from most to least important, were: Anxiety, Suicide, Depressed Mood, Work, and Guilt (the cognitive symptoms) followed by Somatic, Sleep, Appetite & Weight, and Retardation (the somatic symptoms). Participants valued reductions that resulted in posttreatment scores of zero more than expected, given the magnitude of the reductions. Conclusions: The value of reductions in symptoms captured by the HRSD, as judged by patients, appears to differ as a function of symptom category and the post-treatment score. Similar patterns might characterize other measures of depression severity.
Journal article
by Thomas T. Kim, Colin Xu and Robert J. DeRubeis
Within mental health, approaches to determine whether a patient experienced "meaningful " change from treatment have predominantly involved imposing thresholds on three types of metrics derived from assessments of symptom severity: end score (posttreatment score), absolute change (pre-minus posttreatment score), and proportion of change. However, none of these approaches have considered input from the consumer. This study examined correspondences between various reductions from pre-to posttreatment symptom severity levels and patients' judgments of satisfaction with change. Former or currently depressed patients were asked to provide judgments of their satisfaction reflected in vignettes that used descriptions from the Hamilton Rating Scale for Depression. Judgments from 108 female participants were fit using four metrics: end score, absolute change, proportion of change, and the combination of end score and absolute change. Akaike information criteria (AICs) and Akaike weights were used to determine the best-fitting model. Cutoffs were calculated for the five levels of satisfaction with change. Proportion of change best accounted for variation in the patients' ratings. For "slightly ... , " "somewhat ... , " "moderately ... , " and "very ... , " the proportions of reduction that corresponded with each of these ratings of satisfaction were, respectively: 17%, 39%, 62%, and 84%. Our a priori level of satisfaction (between "some-what " and "moderately ") corresponded to a 50% reduction in pretreatment severity. This study may provide services some insight into their female patients' satisfaction with change from treatment for depression using only the proportion of reduction from pretreatment severity. A similar procedure could be applied to other diagnostic groups, as well as other constructs that attend to the patient's perspective.
Journal article
Predictive modeling for response to lithium and quetiapine in bipolar disorder
by Thomas T Kim, Steven Dufour, Colin Xu, Zachary D Cohen, Louisa Sylvia, Thilo Deckersbach, Robert J DeRubeis and Andrew A Nierenberg
Lithium and quetiapine are known to be effective treatments for bipolar disorder. However, little information is available to inform prediction of response to these medications. Machine-learning methods can identify predictors of response by examining variables simultaneously. Further evaluation of models on a test sample can estimate how well these models would generalize to other samples.
Data (N = 482) were drawn from a randomized clinical trial of outpatients with bipolar I or II disorder who received adjunctive personalized treatment plus either lithium or quetiapine. Elastic net regularization (ENR) was used to generate models for lithium and quetiapine; these models were evaluated on a test set.
Predictions from the lithium model explained 17.4% of the variance in actual observed scores of patients who received lithium in the test set, while predictions from the quetiapine model explained 32.1% of the variance of patients that received quetiapine. Of the baseline variables selected, those with the largest parameter estimates were: severity of mania; attention-deficit/hyperactivity disorder (ADHD) comorbidity; nonsuicidal self-injurious behavior; employment; and comorbidity with each of two anxiety disorders (social phobia/society anxiety and agoraphobia). Predictive accuracy of the ENR model outperformed the simple and basic theoretical models.
ENR is an effective approach for building optimal and generalizable models. Variables identified through this methodology can inform future research on predictors of response to lithium and quetiapine, as well as future modeling efforts of treatment choice in bipolar disorder.
Journal article
Adding cognitive therapy to antidepressant medications decreases suicidal ideation
by Gabriela K Khazanov, Colin Xu, Steven D Hollon, Robert J DeRubeis and Michael E Thase
Psychotherapy for depression and antidepressant medications have both been associated with decreases in suicidal ideation. Studies have not examined whether adding psychotherapy to antidepressant medications further reduces suicidal ideation relative to medications alone in adults.
Participants (N = 452) were randomized to 7 months of treatment with antidepressant medications or combined treatment with both medications and cognitive therapy for depression. We examined change in the suicide items from the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS) across treatment using Bayesian generalized linear mixed models for non-continuous outcomes.
Suicidal ideation decreased across treatment. When measured with the BDI, participants receiving both cognitive therapy and antidepressant medications showed 17% greater reductions in suicidal ideation relative to those receiving medications alone; this effect remained significant when controlling for depression severity. While the same pattern was observed when suicidal ideation was measured with the HDRS, the effect was smaller (7%) and not statistically significant. When BDI and HDRS scores were combined, participants receiving both therapy and medications showed 9% greater reductions in suicidal ideation relative to those receiving medications alone; this effect was marginally significant when controlling for depression severity.
This is a secondary analysis of a randomized clinical trial designed to treat depression, in which suicidal ideation was assessed using single-item measures.
Adding cognitive therapy to antidepressant medications may reduce suicidal ideation to a greater extent than medications alone. Pending replication, combination treatment may be preferred for individuals with suicidal ideation.
Journal article
by Gabriela K. Khazanov, Colin Xu, Barnaby D. Dunn, Zachary D. Cohen, Robert J. DeRubeis and Steven D. Hollon
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 433 individuals with recurrent/chronic major depressive disorder. Patients were provided with only ADM or both ADM and CT. Overall, higher baseline distress and anhedonia predicted longer times to remission within one year and recovery within three years. When controlling for treatment condition, distress improved prediction of outcomes over and above anhedonia, while anhedonia did not improve prediction of outcomes over and above distress. Interactions with treatment condition demonstrated that individuals with higher distress and anhedonia benefited from receiving CT in addition to ADM, whereas there was no added benefit of CT for individuals with lower distress and anhedonia. Assessing distress and anhedonia prior to treatment may help select patients who will benefit most from CT in addition to ADM. For the treatments and outcome measures tested, utilizing distress to guide treatment planning may yield the greatest benefit.
Book chapter
Research in Clinical Psychology: Social Exclusion and Psychological Disorders
by Klint Fung, Colin Xu, Brianne L. Glazier, Carly A. Parsons and Lynn E. Alden
In this chapter, we review empirical studies that examine the link between social exclusion and a variety of DSM-5 diagnostic categories. The review focuses on longitudinal and experimental studies so as to draw more definitive conclusions about the extent to which exclusion is a vulnerability factor for the development of these disorders. This research reveals that the effects of exclusion are wide-spread and may facilitate the development and maintenance of most adult mental disorders. For certain disorders, such as social anxiety disorder, depression, and borderline personality disorder, symptoms may in turn elicit exclusion, forming an interpersonal cycle that perpetuates the psychopathology. In light of parallels in the patterns observed in the various clinical domains, we propose that social exclusion may be best viewed as a transdiagnostic risk factor. Accordingly, we propose several transdiagnostic factors that may explain both the shared and the specific effects of exclusion in the context of traditional diagnostic labels.
Journal article
by Robert J DeRubeis, John Zajecka, Richard C Shelton, Jay D Amsterdam, Jan Fawcett, Colin Xu, Paula R Young, Robert Gallop and Steven D Hollon
Antidepressant medication (ADM) maintenance treatment is associated with the prevention of depressive recurrence in patients with major depressive disorder (MDD), but whether cognitive behavioral therapy (CBT) treatment is associated with recurrence prevention remains unclear.
To determine the effects of combining CBT with ADM on the prevention of depressive recurrence when ADMs are withdrawn or maintained after recovery in patients with MDD.
A total of 292 adult outpatients with chronic or recurrent MDD who participated in the second phase of a 2-phase trial. Participants had recovered in the first phase of the trial receiving ADM, either alone or in combination with CBT. The trial was conducted in research clinics in 3 university medical centers in the United States. Patients in phase 2 were randomized to receive maintenance of or withdrawal from ADM and were followed up for 3 years. The first and last patients entered phase 2 in August 2003 and October 2009, respectively. The last patient completed phase 2 in August 2012. Data were analyzed from December 2013 to December 2018.
Maintenance of or withdrawal from treatment with ADM.
Recurrence of an MDD episode using longitudinal interval follow-up evaluations; sustained recovery across both phases.
A total of 292 participants (171 women, 121 men; mean [SD] age 45.1 [12.9] years) were included in analyses of depressive recurrence. Maintenance ADM yielded lower rates of recurrence compared with ADM withdrawal regardless of whether patients had achieved recovery in phase 1 with ADM alone (48.5% vs 74.8%; z = -3.16; P = .002; number needed to treat [NNT], 2.8; 95% CI, 1.8-7.0) or ADM plus CBT (48.5% vs 76.7%; z = -3.49; P < .001; NNT, 2.7; 95% CI, 1.9-5.9). Sustained recovery rates differed as a function of phase 2 condition, with maintenance ADM superior to ADM withdrawal (z = 2.90; P = .004; OR, 2.54; 95% CI, 1.37-4.84; NNT, 2.3; 95% CI, 1.5-6.4). Phase 1 condition was not associated with differential rates of sustained recovery (ADM alone vs ADM plus CBT; z = 0.22; P = .83; OR, 1.08; 95% CI, 0.52-2.11; NNT, 26.0; 95% CI, number needed to harm 3.2 to NNT 2.8), nor was there a significant interaction of phase 1 condition and phase 2 condition (z = 0.30; P = .77; OR, 1.14; 95% CI, 0.49-2.88).
Maintenance ADM treatment, but not previous exposure to CBT, was associated with reduced rates of depressive recurrence. In previous studies, when CBT has been provided without ADM, CBT has shown a preventive effect on depressive relapse. Whether CBT also has a preventive effect on depressive recurrence, or if adding ADM interferes with any such preventive effect, remains unclear.
ClinicalTrial.gov identifier: NCT00057577.
Journal article
by Keith Bredemeier, Sadie Larsen, Geetha Shivakumar, Kathleen Grubbs, Carmen McLean, Carmella Tress, David Rosenfield, Rob DeRubeis, Colin Xu and Edna Foa ... (22 authors)
Background: Several efficacious psychological and pharmacological treatments for posttraumatic stress disorder (PTSD) are available; however, the comparative effectiveness of these treatments represents a major gap in the literature. The proposed study will compare the effectiveness of two leading PTSD treatments - Prolonged Exposure (PE) therapy and pharmacotherapy with paroxetine or venlafaxine extended release - as well as the combination of PE and medication. Methods: In a randomized clinical trial, veterans with PTSD (N = 450) recruited across six Veterans Affairs Medical Centers will complete assessments at baseline, mid-treatment (Week 7), post-treatment (Week 14), and follow-up (Weeks 27 and 40). The primary outcome will be change in (both clinician-rated and self-reported) PTSD severity. Depression symptoms, quality of life, and functioning will also be measured and examined as secondary outcomes. Baseline demographic and clinical data will be used to develop "personalized advantage indices " (PAIs), with the goal of identifying who is most likely to benefit from which treatment. Conclusions: This planned trial will yield findings to directly inform clinical practice guidelines for PTSD, by providing comparative effectiveness data to support recommendations about what can be considered the "first -line " treatment option(s) for PTSD. Further, findings from this trial have the potential to guide treatment planning for individual patients, through implementation of PAIs developed from study data, in service of "personalized medicine. "
Works added by years
Year | Works |
---|---|
2015 | 906 |
2016 | 850 |
2017 | 764 |
2018 | 848 |
2019 | 866 |
2020 | 1003 |
2021 | 1015 |
2022 | 1149 |
2023 | 1107 |
2024 | 1118 |
2025 | 648 |
2026 | 2 |