Trial Outcomes & Findings for Opiate Suicide Study in Patients With Major Depression (NCT NCT04116528)

The study included a sequence in which all subjects received an infusion of ketamine and then were to receive either buprenorphine or placebo. The randomization was done prior to ketamine.

Opiate Suicide Study in Patients With Major Depression

Analyses included a modified intention-to-treat population, defined as all randomized participants who received one week of treatment and completed the week 1 assessment of buprenorphine or placebo. A linear mixed-effects model tested the primary hypothesis of efficacy, measured by change in SSI total scores. The model included random effects for patient and fixed effects for treatment group, time as a continuous variable (days of study: 1, 3, 10, 17, 24, 31), and the time-by-treatment group interaction, along with an unstructured covariance matrix. The SSI has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation.

Montgomery-Åsberg Depression Rating Scale (MADRS) is a validated, 10-item rating scale with each item being scored on a scale from 0-6 with a total score ranging from 0-60. Lower scores indicate a decreased severity of depression.

The Hamilton Depression Scale (HAM-D) is a validated rating scale which consists of 17 items. Nine of the items are scored on a scale of 0-4 and 8 items are scored on a scale of 0-2 for a total scoring range of 0-52. A score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates increased severity of depression. In general, the lower the total score the less severe the depression.

peripherally by exploring opioid activity in subjects treated in the ketamine infusion and the sublingual buprenorphine vs. placebo phases by measuring serum metabolites of both ketamine and buprenorphine. The metabolites are measured in ng/mL with a reference interval of 1-10. Any presence of the drug will result in a number within the interval. If none detected, a not established level will be the result.

Levels of the hormone prolactin may be increased by opioids and ketamine in serum.

Moreover, we will apply pupillometry to estimate opioid activity. Levels of drug and opioid activity at specific time points will be correlated with response at that time point. In addition, regression analyses will be used to assess the relative contribution of opioid activity in blood, drug blood level, and pupil measure to improvement in suicidal behavior as well as mood, pain, and insomnia. This aim is exploratory.