Depression and thoughts of self-harm or suicide among gender and sexually diverse people in a regional Australian community.

ISSUES ADDRESSED: There is a paucity of data regarding depression and thoughts of self-harm or suicide among gender and sexually diverse (GSD) people living within Australian regional/rural locations. This study aims to elucidate these issues and fill a critical gap. METHODS: The sample included 91 GSD people from a regional community in South-West Queensland utilising the PHQ-9 to determine presence/severity of depression and self-harm/suicide ideation. These data were drawn from a larger health and wellbeing survey. Raw mean scores were calculated to determine prevalence/severity of clinical symptoms. Bayesian ordinal regression models were employed to analyse between-subgroup differences in depression and self-harm/suicide ideation. RESULTS: Overall, 80.2% of GSD sample experienced depression (35.2% severe, 45.1% mild/moderate) and 41.8% experienced self-harm/suicide ideation in the past two-weeks. Trans and nonbinary people experienced higher levels of depressions than sexually diverse cisgender people. Pansexual and bisexual people experienced higher levels of depression than gay people. Trans people experienced higher prevalence of self-harm/suicide ideation than cisgender and nonbinary people, with no differences between sexuality subgroups. CONCLUSIONS: These findings contribute to deeper and more nuanced insights regarding clinically salient depressive and self-harm/suicide ideation symptoms among trans, nonbinary, bisexual, pansexual and queer people in regional Australian communities, with the aim to ultimately reduce mental health prevalence, improve mental health outcomes and health promotion among GSD people. SO WHAT?: The current findings revealed GSD people experience high prevalence of depression and self-harm/suicide ideation indicating tailored mental health awareness-raising, training and health promotion is warranted to enhance psychological support.

A genome-wide association, polygenic risk score and sex study on opioid use disorder treatment outcomes.

Opioid use disorder continues to be a health concern with a high rate of opioid related deaths occurring worldwide. Medication Assisted Treatments (MAT) have been shown to reduce opioid withdrawal, cravings and opioid use, however variability exists in individual's treatment outcomes. Sex-specific differences have been reported in opioid use patterns, polysubstance use and health and social functioning. Candidate gene studies investigating methadone dose as an outcome have identified several candidate genes and only five genome-wide associations studies have been conducted for MAT outcomes. This study aimed to identify genetic variants associated with MAT outcomes through genome-wide association study (GWAS) and test the association between genetic variants previously associated with methadone dose through a polygenic risk score (PRS). Study outcomes include: continued opioid use, relapse, methadone dose and opioid overdose. No genome-wide significance SNPs or sex-specific results were identified. The PRS identified statistically significant results (p < 0.05) for the outcome of methadone dose (R2 = 3.45 × 10-3). No other PRS was statistically significant. This study provides evidence for association between a PRS and methadone dose. More research on the PRS to increase the variance explained is needed before it can be used as a tool to help identify a suitable methadone dose within this population.

Genetics of cannabis use in opioid use disorder: A genome-wide association and polygenic risk score study.

BACKGROUND: Individuals with an Opioid Use Disorder (OUD) have increased rates of cannabis use in comparison to the general population. Research on the short- and long-term impacts of cannabis use in OUD patients has been inconclusive. A genetic component may contribute to cannabis cravings. AIMS: Identify genetic variants associated with cannabis use through Genome-wide Association Study (GWAS) methods and investigate a Polygenic Risk Score (PRS). In addition, we aim to identify any sex differences in effect size for genetic variants reaching or nearing genome-wide significance in the GWAS. METHODS: The study outcomes of interest were: regular cannabis use (yes/no) (n = 2616), heaviness of cannabis use (n = 1293) and cannabis cravings (n = 836). Logistic and linear regressions were preformed, respectively, to test the association between genetic variants and each outcome, regular cannabis use and heaviness of cannabis use. GWAS summary statistics from a recent large meta-GWAS investigating cannabis use disorder were used to conduct PRS's. Findings are limited to a European ancestry sample. RESULTS: No genome-wide significant associations were found. Rs1813412 (chromosome 17) for regular cannabis use and rs62378502 (chromosome 5) for heaviness of cannabis use were approaching genome-wide significance. Both these SNPs were nominally significant (p<0.05) within males and females, however sex did not modify the association. The PRS identified statistically significant association with cannabis cravings. The variance explained by all PRSs were less than 1.02x10-2. CONCLUSION: This study provides promising results in understanding the genetic contribution to cannabis use in individuals living with OUD.

Cannabis use and opioid relapse: An exploratory survival analysis of prospectively collected data.

Importance: It is known that only minority of patients with opioid use disorder (OUD) receive treatment, of which only a fraction successfully complete treatment as intended. Factors associated with poor treatment outcomes remain unclear, and there is emerging but conflicting evidence that cannabis use may mitigate opioid use. Objective: To analyze predictors of relapse amongst patients receiving buprenorphine-naloxone for OUD and identify the association between cannabis use and time to relapse. Design: Data were prospectively collected between May 2018 and October 2020, and patients were followed for 12 months. Setting: Thirty-one outpatient opioid agonist treatment clinics across Ontario, Canada. Participants: All patients 16 years of age or older receiving buprenorphine-naloxone for OUD who had a urine toxicology screen negative for opioids at baseline were eligible for inclusion. Of the 488 patients consecutively sampled, 466 were included. Exposure: Cannabis use. Main outcome and measure: Relapse to opioid use assessed using urine toxicology screens. We employed a multivariable Cox-proportional hazard model for our analyses. Results: We found that cannabis use was not protective against relapse [hazard ratio (HR) = 1.03, 95% confidence interval (CI): 0.78, 1.36, p = 0.84]. We found that participants who have been in treatment for at least two years had a 44% decrease in the hazard of relapse compared to those in treatment for less than a year (HR = 0.56, 95% CI: 0.34, 0.92, p = 0.021). We also found that the hazard of relapse was 2.6 times higher for participants who were intravenous drug users (HR = 2.61, 95% CI: 1.74, 3.91, p < 0.001), and that for every 1mg increase in the participants' buprenorphine-naloxone dose, the hazard of relapse is 2% greater (HR = 1.02, 95% CI: 1.01, 1.03, p < 0.001). Conclusion: Our analysis failed to show cannabis to be protective against relapse to opioid use in patients receiving buprenorphine-naloxone for OUD. We identified that individuals who inject drugs, are on higher doses of buprenorphine-naloxone, or have been in treatment for less than two years have a higher hazard for relapse. The presence of such factors may thus warrant closer patient follow-up and more stringent treatment protocols to mitigate risk of relapse and potential overdose.

The future of precision medicine in opioid use disorder: inclusion of patient-important outcomes in clinical trials

Opioid use has reached an epidemic proportion in Canada and the United States that is mostly attributed to excess availability of prescribed opioids for pain. This excess in opioid use led to an increase in the prevalence of opioid use disorder (OUD) requiring treatment. The most common treatment recommendations include medication-assisted treatment (MAT) combined with psychosocial interventions. Clinical trials investigating the effectiveness of MAT, however, have a limited focus on effectiveness measures that overlook patient-important outcomes. Despite MAT, patients with OUD continue to suffer negative consequences of opioid use. Patient goals and personalized medicine are overlooked in clinical trials and guidelines, thus missing an opportunity to improve prognosis of OUD by considering precision medicine in addiction trials. In this mixed-methods study, patients with OUD receiving MAT (n=2,031, mean age 39.1 years [SD 10.7], 44% female) were interviewed to identify patient goals for MAT. The most frequently reported patient-important outcomes were to stop treatment (39%) and to avoid all drugs (25%). These results are inconsistent with treatment recommendations and trial outcome measures. We discuss theses inconsistencies and make recommendations to incorporate these outcomes to achieve patient-centered and personalized treatment strategies.

The future of precision medicine in opioid use disorder: inclusion of patient-important outcomes in clinical trials.

Opioid use has reached an epidemic proportion in Canada and the United States that is mostly attributed to excess availability of prescribed opioids for pain. This excess in opioid use led to an increase in the prevalence of opioid use disorder (OUD) requiring treatment. The most common treatment recommendations include medication-assisted treatment (MAT) combined with psychosocial interventions. Clinical trials investigating the effectiveness of MAT, however, have a limited focus on effectiveness measures that overlook patient-important outcomes. Despite MAT, patients with OUD continue to suffer negative consequences of opioid use. Patient goals and personalized medicine are overlooked in clinical trials and guidelines, thus missing an opportunity to improve prognosis of OUD by considering precision medicine in addiction trials. In this mixed-methods study, patients with OUD receiving MAT (n=2,031, mean age 39.1 years [SD 10.7], 44% female) were interviewed to identify patient goals for MAT. The most frequently reported patient-important outcomes were to stop treatment (39%) and to avoid all drugs (25%). These results are inconsistent with treatment recommendations and trial outcome measures. We discuss theses inconsistencies and make recommendations to incorporate these outcomes to achieve patient-centered and personalized treatment strategies.

Social functioning outcomes in men and women receiving medication-assisted treatment for opioid use disorder.

BACKGROUND: Social functioning (SF), the ability to engage with life and fulfill roles may be a salient "patient important outcome" in addiction treatment. It is not known if medication-assisted treatment (MAT) impacts SF in opioid use disorder (OUD). There is a growing evidence to suggest that men and women are impacted differently by OUD. This study is the largest to date to study sex differences in OUD and explore associations between MAT and SF. METHODS: Data were collected from 2736 participants with OUD, enrolled in MAT for varying lengths of time, in outpatient clinics across Ontario. SF was defined according to the Maudsley Addiction Profile's domains of (1) employment, (2) criminal activity, and (3) interpersonal conflict. Using logistic regression analysis, we examined sociodemographic and clinical factors associated with domains of SF. RESULTS: There were 1544 men (56%) and 1192 women (44%) in this study, and ages varied from 17 to 76 years for men and 18 to 69 years for women. At study entry, participants had been on MAT for a median of 2 years. Compared to men, women reported more psychological (mean MAP score 14/40, SD = 9.55, versus 11/40, SD = 8.64; p < 0.001) and physical symptoms (mean MAP score 17/40, SD = 7.70 versus 14/40, SD = 7.74; p < 0.001). More women reported unemployment(74% versus 58%; p < 0.0001) and interpersonal conflict (46% versus 35%; p < 0.0001). Men were more likely than women to report criminal activity (11%, versus 8%; p = 0.001). Psychological symptoms increased the risk of worse SF, across domains, for men and for women. Every year on MAT was associated with a 7% increase in the odds of women engaging with criminal activity (OR = 1.07, 95% CI 1.02, 1.12, p = 0.006). CONCLUSIONS: Men and women had different SF profiles and psychological symptoms scores while on MAT. The length of time on MAT increased the risk of criminal activity in women, and overall, duration of MAT was not associated with improvement in SF. This may suggest that MAT alone may not support continual improvements in SF in OUD.

The association between health conditions and cannabis use in patients with opioid use disorder receiving methadone maintenance treatment.

BACKGROUND: Cannabis is the most commonly used substance among patients in methadone maintenance treatment (MMT) for opioid use disorder. Current treatment programmes neither screen nor manage cannabis use. The recent legalisation of cannabis in Canada incites consideration into how this may affect the current opioid crisis. AIMS: Investigate the health status of cannabis users in MMT. METHOD: Patients were recruited from addiction clinics in Ontario, Canada. Regression analyses were used to assess the association between adverse health conditions and cannabis use. Further analyses were used to assess sex differences and heaviness of cannabis use. RESULTS: We included 672 patients (49.9% cannabis users). Cannabis users were more likely to consume alcohol (odds ratio 1.46, 95% CI 1.04-2.06, P = 0.029) and have anxiety disorders (odds ratio 1.75, 95% CI 1.02-3.02, P = 0.043), but were less likely to use heroin (odds ratio 0.45, 95% CI 0.24-0.86, P = 0.016). There was no association between cannabis use and pain (odds ratio 0.98, 95% CI 0.94-1.03, P = 0.463). A significant association was seen between alcohol and cannabis use in women (odds ratio 1.79, 95% CI 1.06-3.02, P = 0.028), and anxiety disorders and cannabis use in men (odds ratio 2.59, 95% CI 1.21-5.53, P = 0.014). Heaviness of cannabis use was not associated with health outcomes. CONCLUSIONS: Our results suggest that cannabis use is common and associated with psychiatric comorbidities and substance use among patients in MMT, advocating for screening of cannabis use in this population. DECLARATION OF INTEREST: None.