Comparison of the efficacy and safety of adjunctive therapy using Ketamine with Bupronorphine for patients with major depressive disorder and contaminant opium abuse: A randomized double blind, placebo- controlled clinical trial

Comparison the efficacy and safety of adjunctive therapy using ketamine with buprenorphine for of patients with major depressive disorder and concomitant opium abuse.

Double-blind, randomized , placebo-controlled clinical trial with with parallel groups, , phase 2 on 60 patients. Randomization will be performed using Number cruncher software.

This study is performed on patients admitted to Ebn Sina Psychiatric Hospital in Shiraz with a diagnosis of major depressive disorder and concomitant opioid use disorder. Patients are randomly divided into two groups of 30, one receiving ketamine and one receiving buprenorphine. Depression, anxiety and suicidal ideation of patients before and after medication are measured by Beck Depression Inventory, Beck Suicide Inventory and Hamilton Anxiety Inventory.

Patients admitted in the Ebne Sina hospital wards between the ages of ۱۸ and ۶۵ who meet the diagnostic criteria for major depressive disorder and at the same time suffer from opium use disorder. They should not suffer from important psychiatry problems or internal diseases such as heart disorders, lung diseases, rheumatic diseases, Epilepsy, cancer and thyroid disease at same time.

Intervention group A: Patients with major depression and concomitant use of opioids receiving ketamine injection and placebo oral drug Intervention group B: Patients with major depression and concomitant use of opioids receiving placebo injection and oral buprenorphine

Depression severity

Random list is created by a statistician using the Number Cruncher statistical system (NCSS statistical software system) using the simple block random method. Then, the eligible patients will be divided into two categories according to a random list by our fellow researcher in charge of the ECT unit of Ebne Sina Hospital (where ketamine treatment is performed by anesthesiologist). All participants and researchers are blind to patient allocation.

Participants, the main researcher, and those who evaluate the outcome to analyze the data and those who prepare the draft article, are kept blinded by blind studies. Only those who have not blinded in this study are nurses responsible for injection of intravenous drugs, which are not involved in the process of evaluating patients before and after intervention. Considering that in both groups, the patients will receive injectable and oral drugs, for blinding the researcher and patient , two types of similar packages with opaque coating will be prepared, which first type contains of normal saline bottle, distilled water vial and bopronurfin pills and the other type package contains normal saline bottle, ketamine vial and placebo pills. Packages are numbered based on the random list. After completing the study, the list of packages will be decoded by the researcher. The nurses that inject the drug will also be reminded that they will not provide information on the content of the packages to researcher or patients. The shape of vials and serum and tablets will be very similar.