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Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report.

ABSTRACT: 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-SR16) 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.

SUBMITTER: Nierenberg AA

PROVIDER: S-EPMC5886713 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report.

Nierenberg A A AA Husain M M MM Trivedi M H MH Fava M M Warden D D Wisniewski S R SR Miyahara S S Rush A J AJ

Psychological medicine 20090522 1

<h4>Background</h4>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.<h4>Method</h4>Participants in primary (n=18) and psychiatric (n=23) practice setti ...[more]

PMID: 19460188

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Project description:BACKGROUND:The Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder (PERFORM) study has been initiated to better understand the course of a depressive episode and its impact on patient functioning. This analysis aimed to identify sociodemographic and clinical factors associated with failure to achieve remission at month 2 after initiating or switching antidepressant monotherapy and with subsequent relapse at month 6 for patients in remission at month 2. MATERIALS AND METHODS:This was a 2-year observational cohort study in 1,159 outpatients aged 18-65 years with major depressive disorder initiating or undergoing the first switch of antidepressant monotherapy. Factors with P<0.20 in univariate logistic regression analyses were combined in a multiple logistic regression model to which backward variable selection was applied (ie, sequential removal of the least significant variable from the model and recomputation of the model until all remaining variables have P<0.05). RESULTS:Baseline factors significantly associated with lower odds of remission at month 2 were body-mass index ?30 kg/m2 (OR 0.51), depressive episode >8 weeks (OR 0.51), being in psychotherapy (OR 0.51), sexual dysfunction (OR 0.62), and severity of depression (OR 0.87). Factors significantly associated with relapse at month 6 were male sex (OR 2.47), being married or living as a couple (OR 2.73), residual patient-reported cognitive symptoms at 2 months (OR 1.12 per additional unit of Perceived Deficit Questionnaire-5 score) and residual depressive symptoms at 2 months (OR 1.27 per additional unit of Patient Health Questionnaire-9 score). CONCLUSION:Different factors appear to be associated with failure to achieve remission in patients with major depressive disorder and with subsequent relapse in patients who do achieve remission. Patient-reported cognitive dysfunction is an easily measurable and treatable characteristic that may be associated with an increased likelihood of relapse at 6 months in patients who have achieved remission.

Project description:Chronic insomnia tends to "wax and wane" over lifetime. The presence of residual insomnia symptoms is common, especially among naturally remitted individuals. This study aims to examine the features of these residual symptoms and their potential association with future relapse. A population-based data set on the natural history of insomnia was used for this secondary analysis. Residual insomnia symptoms were investigated in those who had insomnia symptoms/syndrome at baseline and achieved full remission (according to predetermined diagnostic algorithm) within the following 1 year. Cox regressions were used to determine the hazard ratio (HR) of each residual symptom for predicting relapse in the next 4 years. The nature and severity of residual symptoms were examined with an extended version of the Insomnia Severity Index (ISI), which incorporates additional items on sleep quality and specific sleep-related daytime impairments (on daytime fatigue, cognitive functioning, mood, interpersonal relationship, and daily activities). In addition, the presence of depressive symptoms and medical conditions were controlled for in investigating risks of insomnia relapse. A total of 434 participants were included in this study (age ranges from 18 to 94; 65.9% female); 248 of them had relapsed within 4 years. The response rate ranged from 78% to 83%. The most frequently reported residual symptoms with at least moderate severity (ISI items ≥2 on 0-4 ISI item scale) were poor "Quality of sleep" (39.2 %), followed by "difficulty maintaining sleep" (DMS; 27%). The most common residual daytime impairments related to insomnia were fatigue (24.7 %), mood disturbances (23%) and cognitive disturbances (22.6%). After controlling for baseline insomnia and depression severity and concurrent physical diseases, impairments of cognition (HR = 1.46), poor quality of sleep (HR = 1.43), disturbed mood (HR = 1.39), being female (HR = 1.36), DMS (HR = 1.35), and fatigue (HR = 1.24) were significantly associated with insomnia relapse in the next 4 years. Moreover, residual poor sleep quality and daytime insomnia symptoms were independent of DMS in predicting relapse. Subgroup regressions according to sex showed that for male participants, residual cognition impairments (HR = 1.98) was the most significant predictors of future relapse, whereas residual DMS (HR = 1.46) significantly predicted relapse for women only. A wide range of residual symptoms exists in individuals with naturally remitted insomnia. Notably, residual DMS is the most common residual nighttime symptom and the only nighttime symptom associated with insomnia relapse. Additionally, perceived poor sleep quality and cognitive, mood, and somatic impairments attributed to sleep disturbances are also related to future relapse. Attention to these residual symptoms when initiating insomnia treatment is warranted to minimize future relapse.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report.

Publications

Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report.

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