Pharmacological Strategies in the Prevention of Relapse After Electroconvulsive Therapy

§Department of Psychiatry, Washington University, St. Louis, MO and ∥Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
The journal of ECT (Impact Factor: 1.39). 01/2013; 29(1). DOI: 10.1097/YCT.0b013e31826ea8c4
Source: PubMed


To determine whether starting antidepressant medication at the start of electroconvulsive therapy (ECT) reduces post-ECT relapse and to determine whether continuation pharmacotherapy with nortriptyline (NT) and lithium (Li) differs in efficacy or adverse effects from continuation pharmacotherapy with venlafaxine (VEN) and Li.

During an acute ECT phase, 319 patients were randomized to treatment with moderate dosage bilateral ECT or high-dosage right unilateral ECT. They were also randomized to concurrent treatment with placebo, NT, or VEN. Of 181 patients to meet post-ECT remission criteria, 122 (67.4%) participated in a second continuation pharmacotherapy phase. Patients earlier randomized to NT or VEN continued on the antidepressant, whereas patients earlier randomized to placebo were now randomized to NT or VEN. Lithium was added for all patients who were followed until relapse or 6 months.

Starting an antidepressant medication at the beginning of the ECT course did not affect the rate or timing of relapse relative to starting pharmacotherapy after ECT completion. The combination of NT and Li did not differ from VEN and Li in any relapse or adverse effect measure. Older age was strongly associated with lower relapse risk, whereas the type of ECT administered in the acute phase and medication resistance were not predictive. Across sites, 50% of the patients relapsed, 33.6% continued in remission 6 months after ECT, and 16.4% dropped out.

Starting an antidepressant medication during ECT does not affect relapse, and there are concerns about administering Li during an acute ECT course. Nortriptyline and VEN were equally effective in prolonging remission, although relapse rates after ECT are substantial despite intensive pharmacology. As opposed to the usual abrupt cessation of ECT, the impact of an ECT taper should be evaluated.

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    • "However, ECT seems to produce more responses than remissions, with greater efficacy in patients with " pseudoresistance " rather than among those suffering from true TRD (Kellner et al., 2006; Rose et al., 2003; Sackeim et al., 1990). Moreover, relapse rates after ECT discontinuation are substantial, even in the presence of continuous post-ECT pharmacological treatment (Prudic et al., 2013; Rabheru, 2012). Deep brain stimulation (DBS) is a novel technique available for the treatment of a number of specific treatment-resistant neurologic and psychiatric disorders (Williams and Okun, 2013). "
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    ABSTRACT: Despite a wide variety of therapeutic interventions for major depressive disorder (MDD), treatment resistant depression (TRD) remains to be prevalent and troublesome in clinical practice. In recent years, deep brain stimulation (DBS) has emerged as an alternative for individuals suffering from TRD not responding to combining antidepressants, multiple adjunctive strategies and electroconvulsive therapy (ECT). Although the best site for TRD-DBS is still unclear, pilot data suggests that the medial forebrain bundle (MFB) might be a key target to accomplish therapeutic efficacy in TRD patients. To explore the anatomic, electrophysiologic, neurocognitive and treatment data supporting the MFB as a target for TRD-DBS. The MFB connects multiple targets involved in motivated behavior, mood regulation and antidepressant response. Specific phenomenology associated with TRD can be linked specifically to the superolateral branch (sl) of the MFB (slMFB). TRD patients who received DBS-slMFB reported high response/remission rates with an improvement in functioning and no significant adverse outcomes in their physical health or neurocognitive performance. Discussion The slMFB is an essential component of a network of structural and functional pathways connecting different areas possibly involved in the pathogenesis of mood disorders. Therefore, the slMFB should be considered as an exciting therapeutic target for DBS therapy to achieve a sustained relief in TRD patients. There is an urgent need for clinical trials exploring DBS-slMFB in TRD. Further efforts should pursue measuring baseline pro-inflammatory cytokines, oxidative stress, and cognition as possible biomarkers of DBS-slMFB response in order to aid clinicians in better patient selection. Copyright © 2014 Elsevier Inc. All rights reserved.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2014; 58. DOI:10.1016/j.pnpbp.2014.12.003 · 3.69 Impact Factor
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    ABSTRACT: High rates of early relapse following electroconvulsive therapy (ECT) are typically reported in the literature. Current treatment guidelines offer little information to clinicians on the optimal nature of maintenance therapy following ECT. The aim of this study was to provide a systematic overview of the existing evidence regarding post ECT relapse. A keyword search of electronic databases was performed for studies appearing in the peer-reviewed literature before January 2013 reporting on relapse rates in responders to an acute course of ECT administered for a major depressive episode. Meta-analyses were performed where appropriate. Thirty-two studies with up to two years' duration of follow-up were included. In modern-era studies of continuation pharmacotherapy, 51.1% (95% CI=44.7-57.4%) of patients relapsed by 12 months following successful initial treatment with ECT, with the majority (37.7%, 95% CI=30.7-45.2%) relapsing within the first six months. The six-month relapse rate was similar in patients treated with continuation ECT (37.2%, 95% CI=23.4-53.5%). In randomised controlled trials, antidepressant medication halved the risk of relapse compared to placebo in the first six months (risk ratio=0.49, 95% CI=0.39-0.62, p<0.0001, number needed to treat=3.3). Despite continuation therapy, the risk of relapse within the first year following ECT is substantial, with the period of greatest risk being the first six months. The largest evidence base for efficacy in post ECT relapse prevention exists for tricyclic antidepressants. Published evidence is limited or non-existent for commonly used newer antidepressants or popular augmentation strategies. Maintenance of well-being following successful ECT needs to be improved.Neuropsychopharmacology accepted article preview online, 18 June 2013; doi:10.1038/npp.2013.149.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 06/2013; 38(12). DOI:10.1038/npp.2013.149 · 7.05 Impact Factor
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    ABSTRACT: Electroconvulsive therapy (ECT) is the most effective treatment for a refractory major depression in the context of both unipolar and bipolar affective disorders. However, the relapse rate within the first 6 months after a successful course of ECT to treat a depressive episode can be as high 50%. Evidence-based strategies to prevent relapse have partial efficacy and are associated with problematic adverse effects limiting their use as long-term treatments. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in treatment-resistant depression with a favorable adverse effect profile. Herein, we describe six patients, four with unipolar and two with bipolar depression, where rTMS was used to maintain response after a successful course of acute and continuation ECT. rTMS was administered once or twice weekly, at 120% of the resting motor threshold. Patients received sequential bilateral rTMS (low frequency right: 600 pulses, then high frequency left: 3000 pulses). The site of stimulation was 6 cm anterior and 1 cm lateral from the site of maximum stimulation of the abductor pollicis brevis muscle. Depressive symptoms were monitored with the quick inventory of depressive symptoms-self rated. Five of the six patients were able to maintain their response status from 6 to 13 months at the time of last observation. The use of rTMS may be an important relapse prevention strategy following an acute course of ECT. Controlled studies comparing rTMS to current evidence-based relapse prevention strategies are warranted.
    Frontiers in Psychiatry 07/2013; 4:73. DOI:10.3389/fpsyt.2013.00073
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