Abstract
A substantial proportion of the burden of depression arises from its recurrent nature. The risk of relapse after antidepressant medication (ADM) discontinuation is high but not uniform. Predictors of individual relapse risk after antidepressant discontinuation could help to guide treatment and mitigate the long-term course of depression. We conducted a systematic literature search in PubMed to identify relapse predictors using the search terms '(depress* OR MDD*) AND (relapse* OR recurren*) AND (predict* OR risk) AND (discontinu* OR withdraw* OR maintenance OR maintain or continu*) AND (antidepress* OR medication OR drug)' for published studies until November 2014. Studies investigating predictors of relapse in patients aged between 18 and 65 years with a main diagnosis of major depressive disorder (MDD), who remitted from a depressive episode while treated with ADM and were followed up for at least 6 months to assess relapse after part of the sample discontinued their ADM, were included in the review. Although relevant information is present in many studies, only 13 studies based on nine separate samples investigated predictors for relapse after ADM discontinuation. There are multiple promising predictors, including markers of true treatment response and the number of prior episodes. However, the existing evidence is weak and there are no established, validated markers of individual relapse risk after antidepressant cessation. There is little evidence to guide discontinuation decisions in an individualized manner beyond overall recurrence risk. Thus, there is a pressing need to investigate neurobiological markers of individual relapse risk, focusing on treatment discontinuation.
Highlights
Depression is a major health issue (Whiteford et al 2013), and a substantial proportion of its burden arises through relapses and chronic courses: more than half of those with a first episode of depression will go on to have a second, and the majority of them will have further episodes (American Psychiatric Association, 2000)
Many of the factors reported on here appear to have robust properties as predictors of relapse or recurrence risk independent of medication discontinuation: number of previous episodes (Berlanga et al 1999; Kendler et al 2000; Burcusa & Iacono, 2007; Hardeveld et al 2010), residual symptoms (Hardeveld et al 2010; Nierenberg et al 2010) and other factors all robustly increase the risk of relapse
The relevant question for the individual patient really is about the differential impact of medication: will this particular person benefit from continuing treatment? This requires understanding and predicting not just overall relapse risk, but the specific consequences of medication discontinuation, i.e. effects within the separate arms
Summary
Depression is a major health issue (Whiteford et al 2013), and a substantial proportion of its burden arises through relapses and chronic courses: more than half of those with a first episode of depression will go on to have a second, and the majority of them will have further episodes (American Psychiatric Association, 2000). Antidepressant medications (ADM) have proven utility in treating acute episodes of depression, and in reducing the risk of relapse (Geddes et al 2003; Kaymaz et al 2008; Glue et al 2010; Sim et al 2015). They are no panacea: not all patients respond to ADMs, not first-line ones The other side of the treatment, the decision about whether to move to (possibly long-term) maintenance therapy or to discontinue, has attracted far less research focused on making individualized predictions. Given the importance of the initial episodes of depression in setting up the long-term course of the disorder (e.g. Kendler et al 2000; Monroe & Harkness, 2005, 2011), this is a very pressing research lacuna
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