Depressive Episode Relapse Similar in Antidepressant Tx vs Placebo

Patients with MDD who initially respond to antidepressant medications have a 30% to 50% chance of relapse within a year of initiating treatment.

New findings reported in The Lancet Psychiatry show similar trajectories of relapse in patients with major depressive disorder (MDD) who continue treatment with antidepressants vs patients who switch to placebo.1

Patients with MDD who initially respond to antidepressant medications have a 30% to 50% chance of relapse within a year after initiating treatment, and they experience an average of 5 to 9 lifetime depressive episodes.2,3 Patterns of relapse must be discerned in order to optimize relapse prevention strategies. 

Trajectory-based models in clinical research “enable the identification of distinct classes of time-dependent treatment responses and the assessment of the effect of treatment on class membership,” wrote the investigators in the present study. “This approach has identified distinct classes of antidepressant response trajectories, including rapid or gradual improvement, transient improvement followed by symptom worsening, or worse outcomes on medication than placebo in non-responders.”

However, this approach had not previously been used to analyze trajectories of relapse in discontinuation trials. To that end, researchers from Yale University School of Medicine examined data from 4 randomized, double-blind, placebo-controlled trials in which patients with MDD (n = 1462) were initially treated with either fluoxetine or duloxetine. During a subsequent discontinuation phase of the trials, patients either continued taking their assigned medication (n = 960) or received a placebo (n = 502). The current researchers modeled relapse trajectories up to 26 weeks during this latter phase, as measured by participants’ scores on the Hamilton Depression Rating Scale.

According to the results, while continued treatment significantly decreased the odds of membership in the relapse trajectory (odds ratio [OR]: 0.47, 95% CI, 0.37-0.61), similar relapse patterns were observed in the active treatment and placebo groups. In addition, there was only a modest protective effect of treatment continuation: 33% of participants on active medication followed a relapse trajectory compared with 46% of participants receiving placebo.

The data further indicate that predictors of membership in the relapse trajectory were female sex (OR: 1.56, 95% CI, 1.23-2.06), a shorter amount of time with a clinical response by week 1 (OR: 1.10, 95% CI, 1.06-1.15), and a higher baseline score on the Clinical Global Impression Scale (OR: 1.28, 95% CI, 1.01–-.62).

“The existence of similar relapse trajectories on active medication and on placebo suggests that there is no specific relapse signature associated with antidepressant discontinuation,” the researchers wrote. “These findings suggest that strategies for reducing or forestalling the return of depression symptoms need to be developed and widely implemented in depression treatment.”

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  1. Gueorguieva RChekroud AM, Krystal JH. Trajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis. Lancet Psychiatry. 2017; pii: S2215-0366(17)30038-X. doi:10.1016/S2215-0366(17)30038-X
  2. Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annu Rev Public Health. 2013;34:119-138. doi:10.1146/annurev-publhealth-031912-114409
  3. Burcusa SL, Iacono WG. Risk for recurrence in depression. Clin Psychol Rev. 2007;27(8):959-985. doi:10.1016/j.cpr.2007.02.005