At screening, subjects were examined and questioned by a board-certified psychiatrist to determine their eligibility, i.e., “severe Opioid Use Disorder”, based on DSM-5 criteria . Prior to each interview, we described the aims of the study and guaranteed confidentiality. All the patients gave written informed consent before entering the research study. The trial was approved and monitored by the Ethics Research Committee of Shiraz University of Medical Sciences, which adheres to the Declaration of Helsinki Ethical Principles for Medical Research involving human subjects.
The interviews and examinations were achieved on the premises of the treatment hospital because it appeared to be a non-threatening and suitable environment.
Patients admitted consecutively to the psychiatric inpatient ward in Shiraz city enrolled in the clinical trial. Only men were selected for the trial because only male patients are admitted to this main referral psychiatric ward. Patients were screened and interviewed to be eligible for the study. They had to meet the DSM-5 criteria for both opioid dependence and major depressive disorder .
Fifty-one suicidal men who fulfilled the DSM-5 criteria for both opioid dependence and major depressive disorder were randomly assigned into three groups (confidentiality was completely discussed and written informed consent was received from the men). Out of 51 patients (each group included 17 patients), four patients refused to take the single dose of buprenorphine (one from the 32-mg dose group and three from the 96-mg dose group). All of the remaining 47 patients obtained only a single high dose of buprenorphine and ended the 3-day trial time.
Suicidal ideation was questioned and assessed by comprehensive and precise interviews with the patients and the persons who accompanied them. Suicidal ideation was also measured using the Iranian translated and validated version of the BSSI . Note that the patients had suicidal ideation before entering the withdrawal phase, so suicidal ideation was not due to opioid withdrawal symptoms.
Everyday opioid use for at least 1 year was a requirement. Patients were excluded if they had a substance use disorder other than opioid use. Likewise, patients who were not interested in recruitment at the start of the clinical trial were excluded.
Sublingual buprenorphine (one dose only) was administered while the patient was in moderate opioid withdrawal. The presence of two or three opioid withdrawal symptoms was considered as constituting mild withdrawal, the presence of four or five symptoms was an indication of moderate withdrawal, and the presence of six or more symptoms was an indication of severe withdrawal . The buprenorphine doses tested were 32 mg, which is the maximum dosage currently used clinically, and two other doses that were twice and three times 32 mg. A placebo group was not included because of the high probability of severe withdrawal without active pharmacological treatment.
In a double-blind manner the patients were randomly placed in one of the three treatment groups. We used a standard randomization procedure produced by computer to obtain a random sample set.
The research team was adequately trained and included an addiction psychiatrist, a general psychiatrist, a general practitioner, a psychologist, a nurse, and a statistician.
The pills all had the same shape and color. The patients and the research staff were blind to the medications for the period of the study. The ratings and interviews were done by a fully trained physician who was unaware of the medications and adverse events.
A psychometric assessment using the BSSI was administered to the inpatients to monitor the level of suicidal ideation  before the development of opioid withdrawal symptoms. Patients randomly obtained 32 mg, 64 mg, or 96 mg of buprenorphine as a single high dose only and were admitted to a psychiatric ward. Since the patients would develop severe withdrawal symptoms if they were not administered buprenorphine, we did not include a placebo control group. Out of 47 patients, 16 (34.04%) received 32 mg, 17 (36.17%) received 64 mg, and 14 (29.78%) received 96 mg of buprenorphine. The patients received buprenorphine (only a single dose) when they developed moderate opioid withdrawal symptoms. The patients were followed for 3 days. The outcome was monitored and measured by daily scoring of suicidal ideation according to the BSSI and also DSM-5 criteria for major depression.
Although our inpatient facility was a controlled environment, for more accuracy and precision, a urine drug screening test via thin-layer chromatography (TLC) was performed. To ensure safety, adverse effects, vital signs, respiration, and gastrointestinal effects were monitored every hour for the first day and then every 6 h.
We advocate using a single dose on an inpatient basis and then having the patients released drug-free without medication assistance and with an appointment for close psychosocial follow-up.
Data analysis was administered using SPSS version 18. Analysis of variance (ANOVA) and Student t test analyses were used to examine for differences in means, and chi-square analyses were used to test for differences in frequencies. Two-sided tests were used at 0.05 levels.