Adjunctive ketamine vs. buprenorphine in co-occurring major depressive disorder and opioid use disorder: a randomized, double-blind clinical trial assessing anxiety symptom severity and craving intensity

BackgroundThe concomitant presence of major depressive disorder (MDD) and opioid use disorder (OUD) poses a formidable clinical challenge, warranting effective interventions that address both psychiatric and addictive components.AimsThis study sought to compare the efficacy of adjunctive ketamine and buprenorphine in mitigating anxiety symptom severity and craving intensity in individuals with co-occurring MDD and OUD.MethodsA randomized, double-blind clinical trial was conducted, involving individuals meeting diagnostic criteria for both MDD and OUD. Participants were randomly assigned to receive adjunctive ketamine or buprenorphine, in conjunction with standard psychiatric and addiction treatments. Anxiety symptom severity and craving intensity were assessed using Hamilton Anxiety Rating Scale (HAM-A), and the Opioid Craving Scale after 2 h, 24 h, and 7 days.ResultsThe findings revealed distinct treatment trajectories, with ketamine demonstrating rapid and substantial reduction in anxiety symptom severity within hours of administration, accompanied by a pronounced decline in opioid craving intensity. In contrast, buprenorphine was associated with a more gradual but sustained improvement in anxiety symptoms over several days, paralleled by a modest initial reduction in opioid craving, followed by persistent attenuation.ConclusionsIn conclusion, this randomized clinical trial provides evidence supporting the efficacy of adjunctive Ketamine and Buprenorphine in reducing anxiety symptoms and craving intensity in patients with co-occurring MDD and OUD.Trial registrationIRCT20211214053411N1.