Personalized (N-of-1) Trials for Depression: A Systematic Review

Personalized (N-of-1) trials are single-patient, crossover-design trials that may be useful for personalizing the selection of depression treatments. We conducted a systematic review of published N-of-1 trials for depression to determine the feasibility and suitability of this methodology for personalizing depression care.

Electronic databases were searched from database inception through October 2016. Studies were selected if they enrolled depressed patients, included a within-subject crossover design, and systematically assessed depressive symptoms during the N-of-1 trial.

Five eligible studies reporting on 47 depressed patients (range, 1-18 patients) were identified. Two studies were conducted among adults with treatment-resistant depression, 1 study among depressed inpatients, and 2 studies among patients from special populations (geriatric nursing home, human immunodeficiency virus-associated encephalopathy). All studies evaluated the effects of pharmacologic treatments (methylphenidate, D-amphetamine, ketamine, and sulpiride). Three studies compared an off-label treatment with placebo, 1 study compared 2 off-label treatments, and 1 study compared escalating doses of an off-label treatment with placebo. All 4 studies with more than 1 participant demonstrated heterogeneous treatment effects. All studies produced data that could personalize treatment selection for individual patients. No studies reported on recruitment challenges, compliance with self-tracking, or satisfaction with participation.

The feasibility of N-of-1 trials for depression was demonstrated for a limited number of second-line pharmacologic treatments in treatment-resistant patients or in patients with comorbidities that would have excluded them from conventional randomized controlled trials. Additional research is needed to determine whether N-of-1 trials are suitable for improving the selection of depression treatments in clinical practice.