Oral Ketamine vs Diclofenac for Mild-to-Moderate Depression in Chronic Headache Patients: A Double-Blind RCT (IRCT201508201556N80, Imam Hospital Tehran)

Six-week, randomised, double-blind, parallel-group outpatient trial (IRCT201508201556N80; Imam Hospital, Tehran University of Medical Sciences, Iran; January–December 2015). Participants: 46 adults aged 20–55 with chronic persistent headache (≥6 months requiring analgesia) and mild-to-moderate MDD (DSM-IV-TR, HDRS-17 score <19). Arms: (1) oral ketamine 50 mg three times daily (150 mg/day); (2) oral diclofenac 50 mg three times daily. Capsules were indistinguishable. Primary outcome: change in HDRS from baseline to weeks 3 and 6. Secondary: HADS depression subscale, response/remission rates, pain VAS, adverse events. Randomisation by computer-generated sequence (1:1, blocks of 4); concealed in sequentially numbered sealed envelopes; participants, investigators and raters blinded.