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Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report
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Background: Many patients with major depressive disorder (MDD) who experience full symptomatic remission after antidepressant treatment still have residual depressive symptoms. We describe the types and frequency of residual depressive symptoms and their relationship to subsequent depressive relapse after treatment with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method: Participants in primary ( n =18) and psychiatric ( n =23) practice settings were openly treated with citalopram using measurement-based care for up to 14 weeks and follow-up for up to 1 year. We assessed 943 (32.8% of 2876) participants who met criteria for remission to determine the proportions with individual residual symptoms and any of the nine DSM-IV criterion symptom domains to define a major depressive episode. At each visit, the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR 16 ) and the self-report Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale were used to assessed depressive symptoms and side-effects respectively. Results: More than 90% of remitters had at least one residual depressive symptom (median=3). The most common were weight increase (71.3%) and mid-nocturnal insomnia (54.9%). The most common residual symptom domains were sleep disturbance (71.7%) and appetite/weight disturbance (35.9%). Those who remitted before 6 weeks had fewer residual symptoms at study exit than did later remitters. Residual sleep disturbance did not predict relapse during follow-up. Having a greater number of residual symptom domains was associated with a higher probability of relapse. Conclusions: Patients with remission of MDD after treatment with citalopram continue to experience selected residual depressive symptoms, which increase the risk of relapse.
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“Less ill patients are known to have a smaller relapse risk overall (e.g. Nierenberg et al. 2010)”
From Predicting relapse after antidepressant withdrawal – a systematic review (2017) · cites this paper as Nierenberg et al. 2010
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“The foregoing cascade approach - which in tegrates aspects of misdiagnosis, non- ad herence, inadequate treatment trials, as well as implementation gaps - underscores the high prevalence of poor outcomes of depression in primary care, of which a significant percentage would be expected to meet crite ria for TRD 10,30,64,71,107,108 .”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [71]
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“A higher number of previous episodes (Berwian, Walter, Seifritz, & Huys, 2017; Kendler, Thornton, & Gardner, 2000), more residual symptoms (Berwian et al., 2017; Nierenberg et al., 2010), and failure to reach remission after acute antidepressant treatment (APA, 2010; Rush et al., 2006) are associated with a greater risk of relapse”
From Relapse prevention with levomilnacipran ER in adults with major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study (2019) · cites this paper as Nierenberg et al., 2010
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“Residual symptom load affects relapse risk overall (Nierenberg et al. 2010)”
From Predicting relapse after antidepressant withdrawal – a systematic review (2017) · cites this paper as Nierenberg et al. 2010
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“This was highlighted in the STAR * D trial, in which it was ob served that only 10% of persons 'in re mission' were fully asymptomatic 71 .”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [71]
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“Further drawbacks of existing TRD defi nitions are that they fail to take into consid eration the social, economic, anamnestic (e.g., adverse childhood experiences) and interpersonal factors which, alone or in combinations, are known to moderate antidepressant response 1,44,47,71,75- 81 .”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [71]
Experimental — accuracy not yet measuredIn the citing paper
“They increase the risk for [10] and seem to be a prodromal symptom of relapse [11].”
From The effects of exercise on sleep in unipolar depression: a systematic review and network meta-analysis (2021) · cites this paper as [10]
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“In addition, patients who had residual depression symptoms despite responding to treatment, had higher risk of recurrence (Serafini et al., 2018; Nierenberg et al., 2010; Judd et al., 1998) [19, 24, 25].”
From Predictors of recurrence of major depressive disorder (2020) · cites this paper as Nierenberg et al., 2010
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Metadata
- Authors
- Nierenberg, A. A., Husain, M. M., Trivedi, M. H., Fava, M., Warden, D., Wisniewski, S. R., Miyahara, S., & Rush, A. J.
- Affiliations
- Massachusetts General Hospital (US)
- The University of Texas Southwestern Medical Center (US)
- University of Pittsburgh (US)
- Corresponding author
- Nierenberg, A. A.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2009-05-22
- Volume
- 40
- Issue
- 1
- Pages
- 41-50
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC5886713
- OpenAlex
- W2150325627
- Cited by
- 458
- References
- 31
- Citations by year
- 2026: 24 · 2025: 23 · 2024: 23 · 2023: 32 · 2022: 35 · 2021: 23 · 2020: 26 · 2019: 34 · 2018: 26 · 2017: 24 · 2016: 25 · 2015: 31 · 2014: 28 · 2013: 34 · 2012: 30
- FWCI
- 16.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services
- Bristol-Myers Squibb
- University of Texas Southwestern Medical Center
- National Institutes of Health (n01mh90003-26-0-0)
- National Institute of Mental Health (N01 MH090003)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
- Keywords
- major depressive disorder, residual depressive symptoms, remission, citalopram, relapse risk, sleep disorders, weight gain, antidepressant side effects, STAR*D trial, QIDS-SR16
- MeSH terms
- Adult, Major Depressive Disorder, Female, Follow-Up Studies, Humans, Sleep Initiation and Maintenance Disorders, Male, Middle Aged, Personality Inventory, Psychometrics, Recurrence, Risk Factors, Citalopram, Weight Gain, Cognitive Behavioral Therapy, Antidepressive Agents, Second-Generation, Kaplan-Meier Estimate, Young Adult
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