Maintenance phase efficacy of sertraline for chronic depression: A randomized controlled trial

Department of Psychiatry, Butler Hospital, Brown University, Providence, RI 02906, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 12/1998; 280(19):1665-72.
Source: PubMed


The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness.
To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression").
A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996.
Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers.
Maintenance treatment with either sertraline hydrochloride (n = 77) in flexible doses up to 200 mg or placebo (n = 84).
A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase.
Time to recurrence of major depression.
Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P = .002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P = .001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P = .005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata.
Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients.

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Available from: Augustus John Rush, Oct 04, 2015
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    • "Forty-six papers met inclusion criteria, constituting 49 samples and 3,454 patients (Klerman et al., 1974; Coppen et al., 1978; Stein et al., 1980; van Praag and de Haan, 1980; Davidson and Raft, 1984; Harrison et al., 1986; Montgomery et al., 1988, 1993, 1998, 2004; Georgotas et al., 1989; Robinson et al., 1991; Doogan and Caillard, 1992; Claghorn and Feighner, 1993; Montgomery and Dunbar, 1993; Anton et al., 1994; Robert and Montgomery, 1995; Bremner and Smith, 1996; Entsuah et al., 1996; Kocsis et al., 1996, 2007; Stewart et al., 1997; Keller et al., 1998; Reimherr et al., 1998; Terra and Montgomery, 1998; Reynolds et al., 1999; Alexopoulos et al., 2000; Rouillon et al., 2000; Schmidt et al., 2000; Gilaberte et al., 2001; Hochstrasser et al., 2001; Klysner et al., 2002; Wilson et al., 2003; Detke et al., 2004; Simon et al., 2004; Amsterdam and Bodkin, 2006; Kamijima et al., 2006; Lustman et al., 2006; McGrath et al., 2006; Perahia et al., 2006, 2009; Gorwood et al., 2007; Cheung et al., 2008; Dobson et al., 2008; Emslie et al., 2008; Rickels et al., 2010). The information extracted from each study is listed in Table A1 in the Appendix. "
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    ABSTRACT: Some evolutionary researchers have argued that current diagnostic criteria for major depressive disorder (MDD) may not accurately distinguish true instances of disorder from a normal, adaptive stress response. According to disorder advocates, neurochemicals like the monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) are dysregulated in major depression. Monoamines are normally under homeostatic control, so the monoamine disorder hypothesis implies a breakdown in homeostatic mechanisms. In contrast, adaptationist hypotheses propose that homeostatic mechanisms are properly functioning in most patients meeting current criteria for MDD. If the homeostatic mechanisms regulating monoamines are functioning properly in these patients, then oppositional tolerance should develop with prolonged antidepressant medication (ADM) therapy. Oppositional tolerance refers to the forces that develop when a homeostatic mechanism has been subject to prolonged pharmacological perturbation that attempt to bring the system back to equilibrium. When pharmacological intervention is discontinued, the oppositional forces cause monoamine levels to overshoot their equilibrium levels. Since depressive symptoms are under monoaminergic control, this overshoot should cause a resurgence of depressive symptoms that is proportional to the perturbational effect of the ADM. We test this prediction by conducting a meta-analysis of ADM discontinuation studies. We find that the risk of relapse after ADM discontinuation is positively associated with the degree to which ADMs enhance serotonin and norepinephrine in prefrontal cortex, after controlling for covariates. The results are consistent with oppositional tolerance, and provide no evidence of malfunction in the monoaminergic regulatory mechanisms in patients meeting current diagnostic criteria for MDD. We discuss the evolutionary and clinical implications of our findings.
    Frontiers in Psychology 07/2011; 2:159. DOI:10.3389/fpsyg.2011.00159 · 2.80 Impact Factor
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    • "We assessed depression symptoms using the Quick Inventory of Depressive Symptoms (QIDS). Because the QIDS has a wide scoring range, it can be used to detect depressive illness in populations with moderate and low-level symptoms, and is sensitive to change over time (Keller et al. 1998). It is also valid in the post-partum period (Yonkers et al. 2001). "
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    ABSTRACT: Violent trauma is common in urban communities. We explored the hypothesis that past trauma could moderate the effect of a cognitive behavioral intervention designed to prevent depression among urban, low-income mothers. Synthesis of two pilot randomized trials of problem solving education (PSE) among 93 mothers of children hospitalized in the neonatal intensive care unit or enrolled in community-based Early Intervention programs. Outcomes included depressive symptoms, perceived stress, and social functioning. Results were adjusted for baseline depressive symptoms, then stratified according to subjects' trauma history. Fifteen of the 44 PSE subjects (34%) experienced a moderately severe depressive symptom episode during the 3-month follow-up period, as opposed to 21 of 45 control subjects (47%), for a nearly significant adjusted odds ratio (aOR) of 0.36 (95% CI: 0.13, 1.02). Among mothers without trauma histories, far fewer PSE mothers (5 of 24; 21%) experienced an episode of moderately severe depressive symptoms than control mothers (12 of 26; 46%) for a significant aOR of 0.15 (95% CI: 0.03, 0.79). Conversely, among mothers with trauma histories, a similar proportion of PSE mothers (10 of 19; 53%) experienced an episode of moderately severe depressive symptoms as control mothers (9 of 19; 47%). Similar trends held for perceived stress and social functioning. PSE may be more effective at preventing depression among mothers without trauma histories. Our results are consistent with the depression treatment literature, but are novel because they support the principle of intervention moderation in risk prevention, as opposed to treatment, paradigm.
    Depression and Anxiety 06/2011; 28(6):478-84. DOI:10.1002/da.20817 · 4.41 Impact Factor
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    • "Recurrence is associated with a positive feedback so that with each episode there is an increasing probability of another episode [11] [12]. Randomized controlled trials have demonstrated that maintenance antidepressant therapy may reduce relapse in the first year after an acute episode [13] [14]. The American Psychiatric Association practice guideline and the NIMH collaborative study group have recommend maintenance therapy for recurrent major depressive illness [15] [16]. "
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