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Importance: Postpartum depression (PPD) affects as many as 20% of mothers, yet just 1 in 10 of these women receives evidence-based treatment. The COVID-19 pandemic has increased PPD risk, reduced treatment access, and shifted preferences toward virtual care. Objective: To determine whether an online 1-day cognitive behavioral therapy (CBT)-based workshop added to treatment as usual improves PPD, anxiety, social support, mother-infant relationship quality, and infant temperament more than treatment as usual alone. Design, Setting, and Participants: This randomized clinical trial included 403 women with PPD who were recruited across Ontario, Canada, during the COVID-19 pandemic (April 20 to October 4, 2020). Women with Edinburgh Postnatal Depression Scale (EPDS) scores of at least 10 who were 18 years or older and had an infant younger than 12 months were eligible. Interventions: Women were randomly assigned to receive a live, interactive online 1-day CBT-based workshop delivered by a registered psychotherapist, psychiatrist, or clinical psychology graduate student in addition to treatment as usual (n = 202) or to receive treatment as usual and wait-listed to receive the workshop 12 weeks later (n = 201). Main Outcomes and Measures: The primary outcome was change in PPD (EPDS scores) in experimental and wait list control groups 12 weeks after baseline. Secondary outcomes included maternal anxiety (7-item Generalized Anxiety Disorder Questionnaire [GAD-7]), social support (Social Provisions Scale), quality of the mother-infant relationship (Postpartum Bonding Questionnaire), and infant temperament (Infant Behavior Questionnaire-Revised Very Short Form). Results: Participants all identified as women with a mean (SD) age of 31.8 (4.4) years. The workshop led to significant mean (SD) reductions in EPDS scores (from 16.47 [4.41] to 11.65 [4.83]; B = -4.82; P < .001) and was associated with a higher odds of exhibiting a clinically significant decrease in EPDS scores (odds ratio, 4.15; 95% CI, 2.66-6.46). The mean (SD) GAD-7 scores decreased from 12.41 (5.12) to 7.97 (5.54) after the workshop (B = -4.44; 95% CI, -5.47 to -3.38; P < .001) and participants were more likely to experience a clinically significant change (odds ratio, 3.09; 95% CI, 1.99-4.81). Mothers also reported improvements in bonding (B = -3.22; 95% CI, -4.72 to -1.71; P < .001), infant-focused anxiety (B = -1.64; 95% CI, -2.25 to 1.00; P < .001), social support (B = 3.31; 95% CI, 1.04 to 5.57; P < .001), and positive affectivity/surgency in infants (B = 0.31; 95% CI, 0.05 to 0.56; P < .001). Conclusions and Relevance: In this randomized clinical trial, an online 1-day CBT-based workshop for PPD provides an effective, brief option for mothers, reducing PPD and anxiety as well as improving social support, the mother-infant relationship, and positive affectivity/surgency in offspring. Trial Registration: ClinicalTrials.gov Identifier: NCT04485000.

Relapse and recurrence following recovery from Major Depressive Disorder (MDD) are common and debilitating outcomes that carry enormous person, familial and societal costs1. Maintenance antidepressant monotherapy (M-ADM), the current standard for depressive relapse prophylaxis2 is effective as long as it is continued, yet in practice, this plan is compromised by rates of patient noncompliance that can reach 40%3,4. Alternatives to long term antidepressant monotherapy, especially those that address mood outcomes in a broader context of well-being, may appeal to patients wary of continued intervention. One such approach involves the use of sequenced, phase-specific depression treatments within an envelope spanning both acute phase and post-remission care5. Such models involve treating patients to remission pharmacologically and then providing psychotherapy aimed at preventing relapse by teaching affect regulation and self-management skills to be used during recovery. Implicit here is the view that the mechanisms underlying the onset of a depressive episode differ from those responsible for its return6 and that unique interventions are required to address each. Prevention outcomes from the sequential treatment of mood disorders are largely supportive of the approach. Fava7,8 reported lower relapse rates at 4 year follow up and fewer multiple relapses for remitted patients who discontinued medication and received CBT, compared to clinical management. Frank et al.,9 found that time to recurrence was greater for patients who discontinued antidepressants at remission and received Interpersonal Therapy (IPT) or IPT and pill placebo (PLA) versus PLA alone. Similar findings have been obtained with Mindfulness-Based Cognitive Therapy (MBCT), a group intervention designed to train recovered, recurrently depressed patients to disengage from dysphoria-activated depressogenic thinking that increases risk for relapse/recurrence. In addition, MBCT’s emphasis on the daily practice of health enhancing behaviours such as meditation or yoga is a positive incentive for the type of long term engagement required by any maintenance therapy. To date, this intervention designed to be suitable for patients achieving remission via antidepressant treatment, has been evaluated in 3 RCTs with outcomes suggesting a 50% reduction in relapse for patients receiving MBCT compared to treatment as usual10,11 or no difference in survival compared to maintenance pharmacotherapy12. These data, while encouraging, do not address the frequently encountered clinical scenario where a remitted patient wishes, whether for reasons of preference13, side effect burden14 or suitability15, (e.g. pregnancy) to discontinue antidepressant treatment but requires additional prophylactic care. Although previous studies have enrolled patients who were already in remission, no study has explicitly treated patients to remission pharmacologically with the aim of testing MBCT’s prevention effects directly following discontinuation, against active treatment or a placebo (PLA) control. Addressing this question would help determine MBCT’s generalizability to real world clinical settings and evaluate, more broadly, the sequential staging through which both treatments are delivered. The present study was designed to test the relative efficacy of MBCT and M-ADM (versus PLA and clinical management) for prevention of relapse in patients with recurrent depression who have achieved remission through antidepressant pharmacotherapy. We predicted that both MBCT and M-ADM would offer effective protection when compared against PLA and that the level of protection achieved by MBCT would not differ from that provided by M-ADM.