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Question
Question: What is the risk of relapse after electroconvulsive therapy (ECT) for major depression, and what is the most effective maintenance therapy to prevent relapse?
Outcomes: Relapse rates 6 months after last ECT, defined as the proportion of participants meeting the relapse criteria for each study. People taking maintenance antidepressants were compared with those receiving continuation ECT (C-ECT) at a reduced schedule.
Methods
Design: Systematic review with meta-analyses.
Data sources: EMBASE, PubMed, CINAHL, PsycINFO and Cochrane Library databases were searched from inception to January 2013, supplemented by a hand search of reference lists.
Study selection and analysis: Prospective studies in adults (aged 18 years or older) with a major depressive episode (unipolar or bipolar, according to formal diagnostic criteria or clinical judgement) who received an acute course of ECT. Clinical outcomes had to be assessed by patient interviews at least 3 months after ECT. Exclusions: retrospective studies, studies with fewer than 10 participants, comorbid dementia, unstable medical conditions, non-affective psychosis or neurological disease. Two reviewers rated the study quality and extracted data. Heterogeneity was assessed using the I2 statistic; publication bias was assessed using funnel plots. Mean relapse rates were calculated using a random effects model. Relative risks and number needed to treat (NNT) were calculated for direct comparisons of different maintenance treatments.
Main results
Thirty-two studies with up to 2 years of follow-up met the inclusion criteria. Only modern era studies (post-Diagnostic and Statistical Manual of Mental Disorders, third edition) were included in the meta-analysis. The 6-month relapse rate for participants taking maintenance antidepressants was 37.7% (95% CI 30.7% to 45.2%; 17 studies, n=710). At 1 year post-ECT, half of the participants taking maintenance antidepressants had relapsed (51.1%, 95% CI 44.7% to 57.4%; 8 studies, n=348). The 6-month relapse rate for participants receiving C-ECT was 37.2% (95% CI 23.4% to 53.5%; four studies, n=146). The 6-month relapse rate among people taking any form of maintenance (antidepressants or C-ECT) was 39.5% (95% CI 31.9% to 47.7%; 19 studies, n=1001). The 6-month relapse rate for people taking placebo was 78% (95% CI 66.1% to 86.5%; four studies, n=65). In seven randomised control trails (n=402), maintenance antidepressants reduced the risk of relapse compared with placebo (RR=0.49, 95% CI 0.39 to 0.62) with NNT of 3.3. People in these studies were predominantly taking tricyclic antidepressants (TCAs), with limited evidence for newer antidepressants.
Conclusions
Six months after ECT for major depression, over a third of people taking maintenance antidepressants have relapsed. Similar relapse rates were seen for people receiving C-ECT. Nevertheless, maintenance antidepressants significantly reduce the risk of relapse compared with placebo, though evidence is limited to TCAs.
Abstracted from
Commentary
Electroconvulsive therapy (ECT) is widely acknowledged as the most effective acute treatment for severe depression and some psychotic disorders. ECT remains a standard treatment in psychiatric medicine.1 However, its use is limited because it has been stigmatised by sensationalist media portrayals and by exaggerated fears of memory loss. Recently, the durability of antidepressant response to ECT has received considerable attention.2
Jelovac and colleagues’ review of depressive relapse after ECT leads to the recommendation that aggressive continuation therapy (pharmacotherapy or continuation/maintenance ECT (C/M-ECT), or both) be instituted after ECT. The data are compelling that antidepressant pharmacotherapy confers some protection against relapse in the critical months immediately following ECT. The evidence for C/M-ECT (often outpatient), while much smaller, is also convincing.
These data are inadequate to guide the specific medication choice for post-ECT prophylaxis. Much of the trial data involves tricyclic antidepressants and lithium, medications viewed as ‘obsolete’. Data on the prophylactic value of newer antidepressants and second-generation antipsychotics are urgently needed. Because most clinical trials strictly limit pharmacotherapy choices or C/M-ECT schedule flexibility, it is possible that relapse rates are lower in clinical practice. Polypharmacy (eg, antidepressant plus mood stabiliser) with flexible dosing is often prescribed in these very ill patients. It is likely that combining polypharmacy with C/M-ECT would be a particularly protective strategy.
It is unclear why relapse rates after successful ECT are so high, or why they have increased over time. Possibilities include weaker ECT in the modern era and/or changing patient characteristics (eg, more heterogeneous diagnoses, longer episode duration before referral to ECT).
These data show that approximately half of the seriously depressed patients who remit with ECT will have a durable remission. This is an important ‘glass half full’ outcome in patients who are both severely ill and treatment-resistant. The Jelovac et al review should encourage practitioners to offer aggressive and flexible pharmacotherapy, possibly combined with C/M-ECT, to most patients after ECT. Clearly, post-ECT relapse rates need to be reduced by finding more effective continuation treatment strategies.
Footnotes
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Sources of funding Health Research Board; Friends of St Patrick's Hospital.
Footnotes
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Competing interests CK is a Co-Principal Investigator on the National Institute of Mental Health-funded study, Prolonging Remission in Depressed Elderly (PRIDE), which compares pharmacotherapy alone versus pharmacotherapy combined with continuation ECT to prevent relapse in geriatric depression.