Phenotypic analysis of 23andMe survey data: Treatment-resistant depression from participants’ perspective

•The Antidepressant Efficacy Questionnaire (AEQ) identified traits for treatment-resistant depression (TRD).•Vulnerability characteristics distinguished TRD from non-TRD.•Individuals with TRD suffer greater disease burden than those with non-TRD. To improve understanding of treatment-resistant depression (TRD) in a large population of individuals with depression, a self-reported antidepressant efficacy survey was designed and administered to 23andMe research participants. Participants with a current depressive episode or with a depressive episode within the last 5 years were queried for the effect of pharmacotherapy during the episode. TRD was defined as non-response to at least two antidepressants taken for at least 5–6 weeks. Non-TRD (NTRD) was defined as responsive to either the first or second medication taken for at least 3–4 weeks. Participants who could not be classified as TRD or NTRD were excluded from the analysis. Approximately 56,000 participants completed the survey, among which approximately 33,000 took medication for a depressive episode. The 3409 participants with self-reported TRD tended to have younger age of onset, and a more persistent course prior to initiation of treatment (e.g., a longer prior average episode duration and residual symptoms between episodes) than the 18,511 participants classified as NTRD. This survey identified depression characteristics, comorbidities, trigger events, and early childhood trauma that distinguish TRD from NTRD.