Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: A STAR*D report. Psychological Medicine, 40(1), 41-50

Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA.
Psychological Medicine (Impact Factor: 5.94). 06/2009; 40(1):41-50. DOI: 10.1017/S0033291709006011
Source: PubMed


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.
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.
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.
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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    • "Contents lists available at ScienceDirect journal homepage: well as a greater societal and economic burden through loss of work productivity and greater healthcare usage and cost (Paykel et al., 1995; McIntyre and O'Donovan, 2004; Mauskopf et al., 2009; Nierenberg et al., 2010). In a review of findings from 6 observational studies, of those patients not achieving remission, 11–45% were considered to be partial responders to treatment (Mauskopf et al., 2009). "
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    ABSTRACT: Background Remission is the goal in depression, but in practice many patients only experience a partial response to treatment. We sought to determine the prevalence, management and subsequent outcomes of partial responder patients. Methods Patients enrolled in the naturalistic Factors Influencing Depression Endpoints Research (FINDER) study with the Hospital Anxiety and Depression Scale depression subscale (HADS-D) score >10 at baseline who received only SSRI(s) between 0 and 3 months comprised the study cohort (n=1147). Patients were categorized as remitters, partial responders or non-responders at 3 months and then followed up at 6 months. Results At 3 months, 29.4% of the study population were considered non-responders, 27.6% were partial responders, and 39.3% were remitters. Most partial responders at 3 months remained on the same SSRI for the next 3 months. Of the 247 partial responders at 3 months and remained on the same SSRI(s) between 3 and 6 months, 10.9% met criteria for non-response at 6 months, 32.4% remained partial responders, and 56.3% achieved remission. Quality of life outcomes for the partial responders were significantly worse than those in remission (p<0.05). Limitations FINDER was an observational study; the current analysis was conducted post-hoc. Multivariable methods were not applied and findings are primarily descriptive and exploratory. Conclusions Partial response is common and patients in partial response have a poorer quality of life than those achieving remission. Despite this, the majority of partial responders continue to take the same SSRI. Our findings underscore the importance of continuing to strive for remission.
    Journal of Affective Disorders 12/2014; 169:149–156. DOI:10.1016/j.jad.2014.08.003 · 3.38 Impact Factor
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    • "residual symptoms and number of previous depressive episodes could contribute to recurrence of major depression (Judd et al., 1998a, 1998b; Hardeveld et al., 2010) whereas sex and socioeconomic status did not (Hardeveld et al., 2010). Other factors that increase risk of recurrence of depression increases dramatically with the number and duration of previous episodes as well as the presence of residual symptoms following the resolution of the depressive episode (Judd et al., 1998a; Nierenberg et al., 2010). Some studies have shown that psychotherapy especially cognitive behavioral therapy (CBT) was effective in preventing MDD relapse (Simons et al., 1986; Evans et al., 1992). "
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    ABSTRACT: The acute efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder (MDD) is well established; however their role in longer-term prevention of recurrence remains unconfirmed. This study aims at examining: the prophylactic efficacy of four commonly used SSRIs in MDD in a naturalistic setting with long-term follow-up, the effect of concomitant cognitive behavioral therapy (CBT), and the predictors of outcome. In a prospective cohort study, 387 patients who either remitted or responded following treatment with four different SSRIs-fluoxetine, escitalopram, sertraline and paroxetine-were followed up over several years. During an average follow-up period of 34.5 months, 76.5% of patients experienced MDD recurrence. Escitalopram and fluoxetine showed a numerically higher prophylactic efficacy than paroxetine and sertraline but the difference was statistically insignificant. The prophylactic efficacy for SSRI-only treatment was limited, with a recurrence rate of 82.0%, compared to 59.0% of patient recurrence rate in concomitant Cognitive Behavioral Therapy (CBT). The relatively small size of the CBT group and the lack of randomization may undermine the extrapolation of its findings to clinical practice. Nevertheless, the study preliminary data may help in defining the clinical utility of antidepressants and CBT in the prophylaxis from MDD recurrence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research 11/2014; 225(3). DOI:10.1016/j.psychres.2014.11.022 · 2.47 Impact Factor
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    • "Evidence of the long-term efficacy of vortioxetine was shown in a placebo-controlled relapse-prevention study. Relapse after full remission in MDD is common after antidepressant treatment, especially in patients who experience residual symptoms such as sleep or appetite disturbances (Nierenberg et al., 2010). Relapse may occur if treatment is stopped as soon as symptomatic relief is obtained, but continued maintenance antidepressant treatment may reduce the risk of relapse (Geddes, 2003). "
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    ABSTRACT: Vortioxetine, a novel antidepressant for the treatment of major depressive disorder (MDD), is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and serotonin (5-HT) transporter (SERT) inhibitor. Here we review its preclinical and clinical properties and discuss translational aspects. Vortioxetine increases serotonergic, noradrenergic, dopaminergic, cholinergic, histaminergic and glutamatergic neurotransmission in brain structures associated with MDD. These multiple effects likely derive from its interaction with 5-HT-receptor-mediated negative feedback mechanisms controlling neuronal activity. In particular, 5-HT3 receptors may play a prominent role, since their blockade i) increases pyramidal neuron activity by removing 5-HT3 receptor-mediated excitation of GABA interneurons, and ii) augments SSRI effects on extracellular 5-HT. However, modulation of the other 5-HT receptor subtypes also likely contributes to vortioxetine's pharmacological effects. Preclinical animal models reveal differences from SSRIs and SNRIs, including antidepressant-like activity, increased synaptic plasticity and improved cognitive function. Vortioxetine had clinical efficacy in patients with MDD: 11 placebo-controlled studies (including one in elderly) with efficacy in 8 (7 positive, 1 supportive), 1 positive active comparator study plus a positive relapse prevention study. In two positive studies, vortioxetine was superior to placebo in pre-defined cognitive outcome measures. The clinically effective dose range (5-20mg/day) spans ~50 to >80% SERT occupancy. SERT and 5-HT3 receptors are primarily occupied at 5mg, while at 20mg, all targets are likely occupied at functionally relevant levels. The side-effect profile is similar to that of SSRIs, with gastrointestinal symptoms being most common, and a low incidence of sexual dysfunction and sleep disruption possibly ascribed to vortioxetine's receptor modulation. [250 words].
    Pharmacology [?] Therapeutics 07/2014; 145. DOI:10.1016/j.pharmthera.2014.07.001 · 9.72 Impact Factor
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