Machmutow K, Meister R, Jansen A, et al. Comparative effectiveness of continuation and maintenance treatments for persistent depressive disorder in adults. Cochrane Database Syst Rev. 2019 May 20;5:CD012855. doi: 10.1002/14651858.CD012855.pub2. (Systematic review)

BACKGROUND: Persistent depressive disorder (PDD) is defined as a depressive disorder with a minimum illness duration of two years, including four diagnostic subgroups (dysthymia, chronic major depression, recurrent major depression with incomplete remission between episodes, and double depression). Persistent forms of depression represent a substantial proportion of depressive disorders, with a lifetime prevalence ranging from 3% to 6% in the Western world. Growing evidence indicates that PDD responds well to several acute interventions, such as combined psychological and pharmacological treatments. Yet, given the high rates of relapse and recurrences of depression following response to acute treatment, long-term continuation and maintenance therapy are of great importance. To date, there has been no evidence synthesis available on continuation and maintenance treatments of PDDs.

OBJECTIVES: To assess the effects of pharmacological and psychological (either alone or combined) continuation and maintenance treatments for persistent depressive disorder, in comparison with each other, placebo (drug/attention placebo/non-specific treatment control), and treatment as usual (TAU). Continuation treatments are defined as treatments given to currently remitted people (remission is defined as depressive symptoms dropping below case level) or to people who previously responded to an antidepressant treatment. Maintenance therapy is given during recovery (which is defined as remission lasting longer than six months).

SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 28 September 2018. An earlier search of these databases was also conducted for RCTs via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 Dec 2015). In addition we searched grey literature resources as well as the international trial registers ClinicalTrials.gov and ICTRP to 28 September 2018. We screened reference lists of included studies and contacted the first author of all included studies.

SELECTION CRITERIA: We included randomized (RCTs) and non-randomized controlled trials (NRCTs) in adults with formally diagnosed PDD, receiving pharmacological, psychological, or combined continuation and maintenance interventions.

DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted and analyzed data. The primary efficacy outcome was relapse/recurrence rate of depression. The primary acceptance outcome was dropout due to any reason other than relapse/recurrence. We performed random-effects meta-analyses using risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).

MAIN RESULTS: We included 10 studies (seven RCTs, three NRCTs) involving 840 participants in this review, from which five studies investigated continuation treatments and five studies investigated maintenance treatments. Overall, the included studies were at low-to-moderate risk of bias. For the three NRCTs, the most common source of risk of bias was selection of reported results. For the seven RCTs, the most common sources of risk of bias was non-blinding of outcome assessment and other bias (especially conflict of interest due to pharmaceutical sponsoring).Pharmacological continuation and maintenance therapiesThe most common comparison was antidepressant medication versus tablet placebo (five studies). Participants taking antidepressant medication were probably less likely to relapse or to experience a recurrent episode compared to participants in the placebo group at the end of the intervention (13.9% versus 33.8%, RR 0.41, 95% CI 0.21 to 0.79; participants = 383; studies = 4; I² = 54%, moderate quality evidence). Overall dropout rates may be similar between participants in the medication and placebo group (23.0% versus 25.5%, RR 0.90, 95% CI 0.39 to 2.11; RCTs = 4; participants = 386; I² = 64%, low quality evidence). However, sensitivity analyses showed that the primary outcome (rate of relapse/recurrence) showed no evidence of a difference between groups when only including studies with low risk of bias.None of the studies compared pharmacological or psychological treatments versus TAU.Psychological continuation and maintenance therapiesOne study compared psychological therapies versus attention placebo/non-specific control. One study compared psychotherapy with medication. The results of the studies including psychotherapy might indicate that continued or maintained psychotherapy could be a useful intervention compared to no treatment or antidepressant medication. However, the body of evidence for these comparisons was too small and uncertain to draw any high quality conclusions.Combined psychological and pharmacological continuation and maintenance therapiesThree studies compared combined psychological and pharmacological therapies with pharmacological therapies alone. One study compared combined psychological and pharmacological therapies with psychotherapeutic therapies alone. However, the body of evidence for these comparisons was too small and uncertain to draw any high quality conclusionsComparison of different antidepressant medications Two studies reported data on the direct comparison of two antidepressants. However, the body of evidence for this comparison was too small and uncertain to draw any high quality conclusions.

AUTHORS' CONCLUSIONS: Currently, it is uncertain whether continued or maintained pharmacotherapy (or both) with the reviewed antidepressant agents is a robust treatment for preventing relapse and recurrence in people with PDD, due to moderate or high risk of bias as well as clinical heterogeneity in the analyzed studies.For all other comparisons, the body of evidence was too small to draw any final conclusions, although continued or maintained psychotherapy might be effective compared to no treatment. There is need for more high quality trials of psychological interventions. Further studies should address health-related quality of life and adverse events more precisely, as well as assessing follow-up data.

Discipline Area Score
Psychiatry 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
FM/GP/Mental Health 6 / 7
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

Ignoring the bias in the studies, continued medication may help prevent relapse; adjusting for bias, it's difficult to tell. It's difficult to tell whether psychotherapy helps as well. Worth knowing we are stuck with intuition for now until we have more data.

Family Medicine (FM)/General Practice (GP) rater

Whether to continue antidepressants is a frequent question. While the quality of evidence is low, the available evidence is useful.
Comments from EvidenceAlerts subscribers

Dr. Ahmed Elaghoury (5/30/2019 10:20 AM)

This review shows what is known from the SARA*D trial and other well-controlled data. Antidepressants are of short-term and palliative effect, without long-term prevention or modification of illness course. Most of the antidepressant trials are short-term and despite the large databases reviewed here, the authors only included 10 studies. The safety of antidepressant continuation / maintenance did not differ from placebo. I think this review is great and adds to our understanding of antidepressants efficiency. We can help our patients to calm down and start the remission, then we need to think of psychotherapies that give them longer skills and resilience, rather than giving them the risks involved with continuation / maintenance meds.