Repeated measures analysis of opioid use disorder treatment on clinical opiate withdrawal scale in a randomized clinical trial: sex differences.

Purpose: Sex differences may exist in opioid use disorder (OUD) treatment. This study examined the treatment effects of buprenorphine/naloxone (BUP/NX) and methadone (MET) on the Clinical Opiate Withdrawal Scale (COWS) score in individuals with OUD and tested whether the associations differ by sex.

Method: We performed a secondary analysis of the data from the National Drug Abuse Treatment Clinical Trials Network (CTN) protocol-0027. A total of 1269 participants (861 males and 408 females) being aged 18 or older with OUD were randomly assigned to receive BUP/NX (n = 740) or MET (n = 529). The paired t test was initially used to compare the COWS scores between pre-dose and post-dose for BUP/NX and MET treatments, separately. The linear mixed model was used to examine the changes in COWS score adjusted for baseline demographic, substance use, and mental health disorders. The interaction of sex and treatment was detected and stratified analysis by sex was conducted.

Results: The paired t test showed that both BUP/NX and MET treatments significantly reduced the COWS scores (p values <0.0001). BUP/NX revealed higher COWS scores than MET (p = 0.0008) and females demonstrated significantly higher COWS scores than males (p = 0.0169). Stratified by sex, BUP/NX compared with MET revealed higher COWS scores only in males (p = 0.0043), whereas baseline amphetamines use disorder and major depressive disorder were significantly associated with COWS scores in females (p = 0.0158 and 0.0422, respectively).

Conclusions: Both BUP/NX and MET are effective in decreasing opioid withdrawal symptoms via COWS scores, however, treatment plans for OUD by clinical providers should consider sex differences.