Abstract
IMPORTANCE: Given its recurrent nature and burden, major depressive disorder (MDD) warrants reliable methods of relapse prediction. OBJECTIVE: To determine whether actigraphy-derived parameters, measured over 1 to 2 years, are associated with relapse. DESIGN, SETTING, AND PARTICIPANTS: This was an observational cohort study with data collection from July 2016 to January 2019. The setting was multicentric. A referred sample of participants from outpatient psychiatric and primary care clinics across Canada were followed up for 1 to 2 years. Participants had a diagnosis of MDD and Montgomery-Åsberg Depression Rating Scale (MADRS) score less than or equal to 14 at baseline. EXPOSURES: Actigraphy-derived parameters measured over 1 to 2 years. MAIN OUTCOME AND MEASURES: The primary outcome was relapse, defined as any of the following: MADRS score greater than or equal to 22 for 2 consecutive weeks, psychiatric hospitalization, emergence of suicidal intent or behavior, or antidepressant treatment escalation-all adjudicated by an independent panel. Continuous actigraphy data were averaged every 2 weeks. RESULTS: From a referred sample of 102 adults, 93 participants (mean [SD] age, 39.1 [12.7] years; 58 female [62%]) contributed approximately 32 000 complete actigraphy days (median, 46 weeks). In Cox models adjusted for age, sex, season, and baseline MADRS score, baseline lower sleep regularity (hazard ratio [HR], 0.46; 95% CI, 0.28-0.74; P = .002), lower relative amplitude (RA; HR, 0.45; 95% CI, 0.29-0.70; P < .001), lower sleep efficiency (HR, 0.57; 95% CI, 0.38-0.85; P = .005), higher wake after sleep onset (HR, 1.77; 95% CI, 1.12-2.80; P = .01), and higher nighttime activity (HR, 1.86; 95% CI, 1.32-2.62; P < .001) were associated with relapse. In time-varying models, greater composite phase deviation (HR, 1.76; 95% CI, 1.04-2.98; P = .04) and lower RA (HR, 0.45; 95% CI, 0.21-0.97; P = .046) were associated with relapse, with RA remaining significant even after adjusting for concurrent MADRS scores (HR, 0.60; 95% CI, 0.36-0.98; P = .04). Actigraphy significantly differentiated individuals experiencing relapse from those with an ultrastable (MADRS score <14 throughout) and unstable (transient MADRS score, 14-22 without relapse) clinical course. CONCLUSIONS AND RELEVANCE: Actigraphy measures of sleep phase variability and daily activity amplitude were associated with depressive relapse, supporting actigraphy as a potential scalable biomarker to identify high-risk individuals and enable timely, personalized relapse prevention in MDD.