Purpose/Background

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.

Methods/Procedures

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.

Findings/Results

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.

Implications/Conclusions

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.