Meta-analysis of Major Depressive Disorder Relapse and Recurrence With Second-Generation Antidepressants

Division of Pharmaceutical Outcomes and Policy, School of Pharmacy, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.
Psychiatric services (Washington, D.C.) (Impact Factor: 2.41). 11/2008; 59(10):1121-30. DOI: 10.1176/
Source: PubMed


This meta-analysis reviewed data on the efficacy and effectiveness of second-generation antidepressants for preventing major depression relapse and recurrence during continuation and maintenance phases of treatment, respectively.
MEDLINE, EMBASE, and PsycINFO, the Cochrane Library, and International Pharmaceutical Abstracts were searched for the period of January 1980 through April 2007 for reviews, randomized controlled trials, meta-analyses, and observational studies on the topic. Two persons independently reviewed abstracts and full-text articles using a structured data abstraction form to ensure consistency in appraisal and data extraction.
Four comparative trials and 23 placebo-controlled trials that addressed relapse or recurrence prevention were included. Results of comparative trials have not demonstrated statistically significant differences between duloxetine and paroxetine, fluoxetine and sertraline, fluvoxamine and sertraline, and trazodone and venlafaxine. Pooled data for the class of second-generation antidepressants compared with placebo suggested a relatively large effect size that persists over time. For preventing both relapse and recurrence, the number of patients needed to treat is five (95% confidence interval of 4 to 6). Differences in the length of open-label treatment before randomization, drug type, and trial duration did not affect pooled estimates of relapse rates. Across all trials, 7% of patients randomly assigned to receive active treatment and 5% of patients randomly assigned to receive a placebo discontinued treatment because of adverse events.
This review demonstrates the overall benefits of continuation- and maintenance-phase treatment of major depression with second-generation antidepressants and emphasizes the need for additional studies of comparative differences among drugs.

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Available from: Bradley Gaynes, Jan 28, 2014
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    • "Major depressive disorder (MDD) is a chronic disease with a relapsing and remitting course. Antidepressant medications (ADMs) form the front-line treatment for MDD and less than 50% of patients respond or remit to their first treatment (Gartlehner et al., 2012; Hansen et al., 2008). There are currently no objective measures to guide the treatment decisions in MDD, and the clinical standard is to use a " watch and wait " strategy relying on trial and error (Rush et al., 2008). "
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    ABSTRACT: Less than 50% of patients with Major Depressive Disorder (MDD) reach symptomatic remission with their initial antidepressant medication (ADM). There are currently no objective measures with which to reliably predict which individuals will achieve remission to ADMs. 157 participants with MDD from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) underwent baseline MRIs and completed eight weeks of treatment with escitalopram, sertraline or venlafaxine-ER. A score at week 8 of 7 or less on the 17 item Hamilton Rating Scale for Depression defined remission. Receiver Operator Characteristics (ROC) analysis using the first 50% participants was performed to define decision trees of baseline MRI volumetric and connectivity (fractional anisotropy) measures that differentiated non-remitters from remitters with maximal sensitivity and specificity. These decision trees were tested for replication in the remaining participants. Overall, 35% of all participants achieved remission. ROC analyses identified two decision trees that predicted a high probability of non-remission and that were replicated: 1. Left middle frontal volume < 14 · 8 mL & right angular gyrus volume > 6 · 3 mL identified 55% of non-remitters with 85% accuracy; and 2. Fractional anisotropy values in the left cingulum bundle < 0 · 63, right superior fronto-occipital fasciculus < 0 · 54 and right superior longitudinal fasciculus < 0 · 50 identified 15% of the non-remitters with 84% accuracy. All participants who met criteria for both decision trees were correctly identified as non-remitters. Pretreatment MRI measures seem to reliably identify a subset of patients who do not remit with a first step medication that includes one of these commonly used medications. Findings are consistent with a neuroanatomical basis for non-remission in depressed patients. Brain Resource Ltd is the sponsor for the iSPOT-D study (NCT00693849).
    Full-text · Article · Jan 2015 · EBioMedicine
    • "Both these factors as well as other variables (e.g., patient's disorganization) result in lower-thaneffective adherence to prescribed medical regimens. Furthermore, up to 20% of patients taking ADM for two years will experience a depressive recurrence (Hansen et al. 2008, Kocsis et al. 2007), a phenomenon known as depressive recurrence on antidepressant therapy (DRAT) or " poop out " (Dunlop 2013). Finally, even very effective ADM have a high relapse rate, exceeding 50%, even if a medication is taken as a maintenance treatment for 12–15 months (Hollon et al. 2005a). "
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    ABSTRACT: Major depressive disorder (MDD) is among the most frequent and debilitating psychiatric disorders. Efficacious psychotherapy and antidepressant medications have been developed, and two-thirds of depressed patients respond to single-modality treatment; however, only about one-third of patients remit to single-modality treatments with no meaningful differences in outcomes between treatment types. This article describes the major clinical considerations in choosing between single-modality or combination treatments for MDD. A review of the relevant literature and meta-analyses provides suggestions for which treatment to use for which patient and when each treatment or combination should be provided. The review summarizes the moderators of single-modality and combination-treatment outcomes. We describe models of mechanisms of treatment efficacy and discuss recent treatment-specific neurobiological mechanisms of change.
    No preview · Article · Jan 2014 · Annual Review of Psychology
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    • "Strategies to prevent recurrence of a major depressive episode can be highly effective. A meta-analysis found a number needed to treat (NNT) of five (Hansen et al., 2008). In comparison, the number needed to treat to prevent one major cerebrovascular event with aspirin over a mean follow-up of 6.9 years is 253 (Berger et al., 2011). "
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    ABSTRACT: OBJECTIVE: Examine time to recurrence of major depressive disorder (MDD) across different treatment settings and assess predictors of time to recurrence of MDD. METHODS: Data were from 375 subjects with a MDD diagnosis from the Netherlands Study of Depression and Anxiety (NESDA). The study sample was restricted to subjects with a remission of at least three months. These subjects were followed until recurrence or the end of the two year follow-up. DSM-IV based diagnostic interviews and Life Chart Interviews were used to assess time to recurrence of MDD across treatment settings. Predictors of time to recurrence were determined using Cox's proportional hazards analyses. RESULTS: Although trends indicated a slightly higher rate of and shorter time to recurrence in specialized mental health care, no significant difference in recurrence rate (26.8% versus 33.5%, p=0.23) or in time to recurrence (controlled for covariates) of MDD was found between respondents in specialized mental health care and respondents treated in primary care (average 6.6 versus 5.5 months, p=0.09). In multivariable analyses, a family history of MDD and previous major depressive episodes were associated with a shorter time to recurrence. Predictors did not differ across treatment settings. LIMITATIONS: The study sample may not be representative of the entire population treated for MDD in specialized mental health care. CONCLUSIONS: Health care professionals in both settings should be aware of the same risk factors since the recurrence risk and its predictors appeared to be similar across settings.
    Full-text · Article · Dec 2012 · Journal of Affective Disorders
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