Maintenance therapy for chronic depression. A controlled clinical trial of desipramine.

Department of Psychiatry, New York Hospital-Cornell Medical Center, New York, USA.
Archives of General Psychiatry (Impact Factor: 13.75). 10/1996; 53(9):769-74; discussion 775-6.
Source: PubMed

ABSTRACT Previous studies have shown the efficacy of antidepressants in the treatment of chronic depression. We report the results of a long-term study comparing desipramine hydrochloride and placebo for maintenance therapy of remitted patients with chronic depression.
Outpatients who met DSM-III-R diagnostic criteria for "pure" dysthymia (n = 51), dysthymia with current major depression ("double depression") (n = 64), or chronic major depression (n = 14) were treated on an open basis with desipramine. Full and partial remitters after 10 weeks entered a continuation phase of open treatment with desipramine for 16 weeks. Remitted patients then were randomized to continue desipramine treatment or tapered to placebo treatment for a maintenance phase of up to 2 years. Relapse rates and time to relapse during maintenance therapy were compared between the two treatment groups.
Acute-phase treatment results did not differ significantly according to chronic depression subtype. Remission persisted with a high degree of stability during the continuation phase. Relapse rates during the maintenance phase were 52% for the placebo group and 11% for the active desipramine group (chi 2 = 8.1, P = .004). Most placebo relapses occurred during the first 6 months of maintenance therapy. Active medication was significantly more effective than placebo in that subgroup entering the maintenance phase in full remission and in those patients who fulfilled criteria for a diagnosis of pure dysthymia or double depression on entry to the study.
Long-term maintenance treatment with desipramine appeared to be effective in the prevention or postponement of relapse of depression in patients who responded to desipramine during the acute and continuation phases.

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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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    • "forms of major depressive disorders (MDDs; Greden, 2001; Keller et al., 1998; Kocsis et al., 1996; Kupfer et al., 1992). In contrast, few studies have examined the efficacy of continuation and maintenance psychotherapy for depression (Rush & Thase, 1998). "
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    Journal of Consulting and Clinical Psychology 09/2004; 72(4):681-8. DOI:10.1037/0022-006X.72.4.681 · 4.85 Impact Factor
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    • "Several recent studies have demonstrated the efficacy of antidepressants in both acute (Harrison and Stewart 1995; Keller et al 1998; Kocsis et al 1988; Thase et al 1996), continuation (Koran et al, in press), and maintenance (Keller et al 1998; Kocsis et al 1996) treatment of chronic forms of depression. Pharmacologic treatment of chronic depression produces improvements in the associated psychosocial impairments found in these patients (Kocsis et al 1988; Markowitz et al 1996; Miller et al 1998; Stewart et al 1988). "
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