Sex differences in opioid use and medical issues during buprenorphine/naloxone treatment

Abstract

Background: There are sex differences in buprenorphine/naloxone clinical trials for opioid use. Whereas women have fewer opioid-positive urine samples, relative to men, a significant decrease in opioid-positive samples was found during treatment for men, but not women. In order to inform sex-based approaches to improve treatment outcomes, research is needed to determine if opioid use, and predictors of opioid use, differs between men and women during treatment. Objectives: To test for sex differences in opioid use during a buprenorphine/naloxone clinical trial and determine if sex differences exist in the associations between addiction-related problem areas and opioid use over the course of the trial. Method: This secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network (CTN) 0003 examined sex differences (men=347, women=169) in opioid-positive samples in a randomized clinical trial comparing 7-day vs. 28-day buprenorphine/naloxone tapering strategies. Addiction-related problem areas were defined by Addiction Severity-Lite (ASI-L) domain composite scores. Results: Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial (B=.33, p=.01) and medical issues were positively related to submitting an opioid-positive sample during treatment for women (B=1.67, p=.01). No ASI-L domain composite score was associated with opioid-positive samples during treatment for men. Conclusion: Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial, and medical issues predicted opioid use during treatment for women but not men. Complementary treatment for medical problems during opioid replacement therapy may benefit women.

Diversity inclusion in United States opioid pharmacological treatment trials: A systematic review.

“…Furthermore, the samples in the reviewed articles may represent a lower than average SES population, which is consistent with the population of individuals with OUDs—a critical factor to consider, because this group experiences a high level of health disparities related to OUDs (King et al, 2014; Singh et al, 2019). These findings are important given that research suggests that females, people of low SES, and racially/ethnically minoritized individuals experience significant health disparities related to opioid use and may not respond as well to pharmacological treatment (Barbosa-Leiker et al, 2018; Crist et al, 2013; Parran et al, 2010; Pro et al, 2020). Moreover, people who are both low SES and from a minoritized racial/ethnic background may experience even greater, additive, or multiplicative risk for harm related to OUD.…”

“…Of particular concern, none of the reviewed studies reported on the inclusion of gender diverse (e.g., transgender or gender non-binary) individuals. It is further problematic that articles did not differentiate between biological sex and socially constructed gender, as biological sex may differ from expressed gender, but sex can affect efficacy of medications for OUD, making it critical to know whether reported samples are reflecting biological sex or gender identity (Barbosa-Leiker et al, 2018).…”

“…These differences are likely due to biological, environmental, and psychosocial factors, among others. Younger individuals, those with lower SES, and females tend to report worse outcomes following pharmacological treatment for OUD compared to older individuals, those with higher SES, and males (Barbosa-Leiker et al, 2018; Hillhouse et al, 2013; Parran et al, 2010). Although some research suggests there may be specific gene polymorphisms (i.e., variations in the formation of genes) of the OPRD1 gene that are associated with worse buprenorphine treatment outcomes among females but not males (Clarke et al, 2014), these findings are equivocal and need to be replicated in larger, more diverse samples.…”

Sex and Gender Differences in the Effects of Novel Psychoactive Substances

“…Clinical research has revealed numerous sex-dependent differences in terms of patterns of use and response to treatment in opioid addicted patients, with women being more likely to use prescription opioids than men, such as Vicodin ® and Oxycodone [ 187 ], and to benefit from complementary treatment for medical problems during opioid replacement therapy [ 188 ]. Sex-dependent differences have also been observed in pain perception and in the response to opioids for pain relief [ 189 , 190 ].…”

Effectiveness and selectivity of a heroin conjugate vaccine to attenuate heroin, 6-acetylmorphine, and morphine antinociception in rats: Comparison with naltrexone

“…Patient compliance with naltrexone is notoriously poor even when naltrexone is combined with opiate abstinence incentives (Jarvis et al, 2019;Jarvis et al, 2018;Lee et al, 2018). Furthermore, some patients still relapse on current FDA-approved treatments (Barbosa-Leiker et al, 2018;Tkacz et al, 2012) highlighting the need for preclinical research to develop effective and readily accessible candidate OUD treatments.…”