Abstract: 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 therapies The 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 therapies One 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 therapies Three 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 conclusions Comparison 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. 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.

Plain-language summary: According to GRADE, there was moderate quality evidence that participants taking medication treatment probably had less relapses/recurrences and may have lower dropouts than those taking placebo. The risk of depression returning in participants receiving a placebo (instead of antidepressant medicine) was 34%. In comparison, participants who remained on antidepressant medicines had a lower risk for recurrence of 13%. The continued treatment lasted between four months and two years. Antidepressant were as well accepted as placebo. However, as most of the included studies showed risk of bias and there were some inconsistent results between the different studies, it cannot be concluded with certainty whether continued or maintained pharmacotherapy (or both) is a convincing treatment for people with PDD. Additionally, as studies on the long-term effects of medication are lacking, recommendations on the necessary duration of medication treatment cannot be drawn. The benefits of psychological therapies or combined treatment remained unclear, due to the small number of studies. This review cannot provide clear, certain evidence regarding whether continued antidepressant medication (compared to placebo tablet) reduces the risk of depression recurring in adults with persistent depression. However, only a few studies have been done. Further studies should especially address psychological and combined long-term treatments.