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Background: Treatment-seeking people with opioid use disorder (OUD) who are capable of pregnancy need accurate information about the potential impact of medication to treat OUD (MOUD) on fertility to make informed choices about treatment that are consistent with their reproductive wishes. There is a dearth of research on fertility associated with MOUD receipt in birthing people with OUD. Objective: To estimate the association between treatment with MOUD and odds of conception among birthing people using national administrative claims. Design: Retrospective case-crossover study using multi-state US administrative data (2006–2016). Dates of conception were estimated from delivery dates and served as "case" days for which MOUD exposures were compared to those on all other ("control") days of insurance enrollment. Participants: Treatment-seeking people with OUD with a delivery during the observation period. Main measures: Odds ratios for conception from within-person fixed effects models were modeled as a function of exposure to MOUD (buprenorphine, methadone, extended-release depot naltrexone, or oral naltrexone) using conditional logistic regression. Key Results: A total of 21,928 births among 19,133 people with OUD were identified. In the sample, 5873 people received buprenorphine, 1825 methadone, 486 extended-release naltrexone, and 714 oral naltrexone. Participants could receive more than one type of MOUD. Mean age was 28.2 years (SD = 2.2; range = 16–45), with 76.2% having Medicaid. vs. commercial insurance. Compared to no MOUD, periods of methadone (aOR = 0.55 [95% CI = 0.48–0.63]) or buprenorphine receipt (aOR = 0.84 [0.77–0.91]) were associated with fewer conceptions. Treatment periods with extended-release depot naltrexone compared to no medication were associated with higher odds of conception (aOR = 1.75 [1.22–2.50]) and there was no significant difference in conception with oral naltrexone (aOR = 1.02 [0.67–1.54]). Conclusions: The association between MOUD and odds of conception among birthing people varied by type of MOUD, with extended-release naltrexone associated with higher odds of conceiving compared to no treatment. Clinical studies are urgently needed to investigate these findings further. [ABSTRACT FROM AUTHOR]

Background: Potential differences in buprenorphine treatment outcomes across various treatment settings are poorly characterized in multi-state administrative data. We thus evaluated the association of opioid use disorder (OUD) treatment setting and insurance type with risk of buprenorphine discontinuation among commercial insurance and Medicaid enrollees initiated on buprenorphine. Methods: In this observational, retrospective cohort study using the Merative MarketScan databases (2006–2016), we analyzed buprenorphine retention in 58,200 US adults with OUD. Predictor variables included insurance status (Medicaid vs commercial) and treatment setting, operationalized as substance use disorder (SUD) specialty treatment facility versus outpatient primary care physicians (PCPs) versus outpatient psychiatry, ascertained by linking physician visit codes to buprenorphine prescriptions. Treatment setting was inferred based on timing of prescriber visit claims preceding prescription fills. We estimated time to buprenorphine discontinuation using multivariable cox regression. Results: Among enrollees with OUD receiving buprenorphine, 26,168 (45.0%) had prescriptions from SUD facilities without outpatient buprenorphine treatment, with the remaining treated by outpatient PCPs (n = 23,899, 41.1%) and psychiatrists (n = 8133, 13.9%). Overall, 50.6% and 73.3% discontinued treatment at 180 and 365 days respectively. Buprenorphine discontinuation was higher among enrollees receiving prescriptions from SUD facilities (aHR = 1.03[1.01–1.06]) and PCPs (aHR = 1.07[1.05–1.10]). Medicaid enrollees had lower buprenorphine retention than those with commercial insurance, particularly those receiving buprenorphine from SUD facilities and PCPs (aHR = 1.24[1.20–1.29] and aHR = 1.39[1.34–1.45] respectively, relative to comparator group of commercial insurance enrollees receiving buprenorphine from outpatient psychiatry). Conclusion: Buprenorphine discontinuation is high across outpatient PCP, psychiatry, and SUD treatment facility settings, with potentially lower treatment retention among Medicaid enrollees receiving care from SUD facilities and PCPs. [ABSTRACT FROM AUTHOR]

Background: Associations between race/ethnicity and medications to treat OUD (MOUD), buprenorphine and methadone, in reproductive-age women have not been thoroughly studied in multi-state samples. Objective: To evaluate racial/ethnic variation in buprenorphine and methadone receipt and retention in a multi-state U.S. sample of Medicaid-enrolled, reproductive-age women with opioid use disorder (OUD) at the beginning of OUD treatment. Design: Retrospective cohort study. Subjects: Reproductive-age (18–45 years) women with OUD, in the Merative™ MarketScan® Multi-State Medicaid Database (2011–2016). Main Measures: Differences by race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, "other" race/ethnicity) in the likelihood of receiving buprenorphine and methadone during the start of OUD treatment (yes/no) were estimated using multivariable logistic regression. Differences in time to medication discontinuation (days) by race/ethnicity were evaluated using multivariable Cox regression. Results: Of 66,550 reproductive-age Medicaid enrollees with OUD (84.1% non-Hispanic White, 5.9% non-Hispanic Black, 1.0% Hispanic, 5.3% "other"), 15,313 (23.0%) received buprenorphine and 6290 (9.5%) methadone. Non-Hispanic Black enrollees were less likely to receive buprenorphine (adjusted odds ratio, aOR = 0.76 [0.68–0.84]) and more likely to be referred to methadone clinics (aOR = 1.78 [1.60–2.00]) compared to non-Hispanic White participants. Across both buprenorphine and methadone in unadjusted analyses, the median discontinuation time for non-Hispanic Black enrollees was 123 days compared to 132 days and 141 days for non-Hispanic White and Hispanic enrollees respectively (χ2 = 10.6; P =.01). In adjusted analyses, non-Hispanic Black enrollees experienced greater discontinuation for buprenorphine and methadone (adjusted hazard ratio, aHR = 1.16 [1.08–1.24] and aHR = 1.16 [1.07–1.30] respectively) compared to non-Hispanic White peers. We did not observe differences in buprenorphine or methadone receipt or retention for Hispanic enrollees compared to the non-Hispanic White enrollees. Conclusions: Our data illustrate inequities between non-Hispanic Black and non-Hispanic White Medicaid enrollees with regard to buprenorphine and methadone utilization in the USA, consistent with literature on the racialized origins of methadone and buprenorphine treatment. [ABSTRACT FROM AUTHOR]

Key Points: Question: What is the prevalence of gabapentin use in individuals filling buprenorphine prescriptions for opioid use disorder (OUD), and what are its associations with drug-related poisoning? Findings: In this case-control study with crossover analysis of 109 407 individuals diagnosed with OUD initiating buprenorphine treatment, gabapentin use was not associated with hospitalization for drug-related poisoning after accounting for between-person confounding. Meaning: These findings contribute to the evidence base on the use of gabapentin as an adjunctive medication in individuals filling buprenorphine with OUD. This case-control study with crossover analysis assesses the differences between patients receiving and not receiving gabapentin alongside buprenorphine in the treatment of opioid use disorder and the drug-related poisoning risk associated with gabapentin. Importance: Gabapentin prescriptions have drastically increased in the US due to off-label prescribing in settings such as opioid use disorder (OUD) treatment to manage a range of comorbid conditions and withdrawal symptoms, despite a lack of evidence. Objective: To assess the purpose and associated risks of off-label gabapentin use in OUD treatment. Design, Setting, and Participants: This retrospective recurrent-event case-control study with a crossover design used administrative claims data from MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Individuals aged 12 to 64 years with an OUD diagnosis and filling buprenorphine prescriptions were included in the primary analysis conducted from July 1, 2022, through June 1, 2023. Unit of observation was the person-day. Exposures: Days covered by filled gabapentin prescriptions. Main Outcomes and Measures: Primary outcomes were receipt of gabapentin in the 90 days after initiation of buprenorphine treatment and drug-related poisoning. Drug-related poisonings were defined using codes from International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Results: A total of 109 407 patients were included in the analysis (mean [SD] age, 34.0 [11.2] years; 60 112 [54.9%] male). Among the 29 967 patients with Medicaid coverage, 299 (1.0%) were Hispanic, 1330 (4.4%) were non-Hispanic Black, 23 112 (77.1%) were non-Hispanic White, and 3399 (11.3%) were other. Gabapentin was significantly less likely to be prescribed to Black or Hispanic patients, and more likely to be prescribed to female patients, those with co-occurring substance use or mood disorders, and those with comorbid physical conditions such as neuropathic pain. Nearly one-third of persons who received gabapentin (4336 [31.1%]) had at least 1 drug-related poisoning after initiating buprenorphine treatment, compared with 13 856 (14.5%) among persons who did not receive gabapentin. Adjusted analyses showed that days of gabapentin use were not associated with hospitalization for drug-related poisoning (odds ratio, 0.98 [95% CI, 0.85-1.13]). Drug-related poisoning risks did not vary based on dosage. Conclusions and Relevance: Gabapentin is prescribed in the context of a myriad of comorbid conditions. Even though persons receiving gabapentin are more likely to have admissions for drug-related poisoning, these data suggest that gabapentin is not associated with an increased risk of drug-related poisoning alongside buprenorphine in adjusted analyses. More data on the safety profile of gabapentin in OUD settings are needed. [ABSTRACT FROM AUTHOR]

This study uses administrative data to show that pregnancy is a time period of increased opioid use disorder treatment utilization, although treatment discontinuation remains very high. OBJECTIVE: To examine the association between pregnancy and medications for opioid use disorder (MOUD) initiation and discontinuation among reproductive-aged people receiving treatment for opioid use disorder (OUD) in the United States. METHODS: We conducted a retrospective cohort study of people with gender recorded as female, aged 18–45 years, in the MerativeTM MarketScan® Commercial and Multi-State Medicaid Databases (2006–2016). Opioid use disorder and pregnancy status were identified based on inpatient or outpatient claims for established International Classification of Diseases, Ninth and Tenth Revision diagnosis and procedure codes. The main outcomes were buprenorphine and methadone initiation and discontinuation, determined by using pharmacy and outpatient procedure claims. Analyses were conducted at the treatment episode level. Adjusting for insurance status, age, and co-occurring psychiatric and substance use disorders, we used logistic regression to estimate MOUD initiation and used Cox regression to estimate MOUD discontinuation. RESULTS: Our sample included 101,772 reproductive-aged people with OUD, encompassing 155,771 treatment episodes (mean age 30.8 years, 64.4% Medicaid insurance, 84.1% White), of whom 2,687 (3.2%, encompassing 3,325 episodes) were pregnant. In the pregnant group, 51.2% of treatment episodes (1,703/3,325) involved psychosocial treatment without MOUD, in comparison with 61.1% (93,156/152,446) in the nonpregnant comparator group. In adjusted analyses assessing likelihood of initiation for individual MOUD, pregnancy status was associated with an increase in buprenorphine (adjusted odds ratio [aOR] 1.57, 95% CI 1.44–1.70) and methadone initiation (aOR 2.04, 95% CI 1.82–2.27). Discontinuation rates of MOUD at 270 days were high for both buprenorphine (72.4% for nonpregnant episodes vs 59.9% for pregnant episodes) and methadone (65.7% for nonpregnant episodes vs 54.1% for pregnant episodes). Pregnancy was associated with a decreased likelihood of discontinuation at 270 days for both buprenorphine (adjusted hazard ratio [aHR] 0.71, 95% CI 0.67–0.76) and methadone (aHR 0.68, 95% CI 0.61–0.75), in comparison with nonpregnant status. CONCLUSION: Although a minority of reproductive-aged people with OUD in the United States are initiated on MOUD, pregnancy is associated with a significant increase in treatment initiation and a reduced risk of medication discontinuation. [ABSTRACT FROM AUTHOR]

Select Drug Category Stimulants Topic Prenatal/Perinatal Abstract Detail Clinical – Epidemiology Abstract Category Original Research In pregnant people with opioid use disorder (OUD) and attention deficit hyperactivity disorder, the risks and benefits of prescription psychostimulant use are poorly understood. We evaluated the association of prescription psychostimulant use in pregnancy with 1) buprenorphine retention and 2) hospitalization or admission for acute substance use disorder (SUD)-related events. We conducted a secondary analysis of 1,029 pregnant women with OUD (ages 18-45) in the Merative™ MarketScan® Databases (2006-2016) who were initiating treatment with buprenorphine. OUD and pregnancy status were identified using inpatient and/or outpatient claims for diagnostic (ICD 9/10) or procedure (CPT) codes. The main predictor variable was prescriptions for psychostimulant medication to treat ADHD. The main outcomes were 1) buprenorphine discontinuation and 2) risk of hospitalization or emergency admission for acute SUD-related events and drug-related poisoning. We used multivariable cox regression models to estimate buprenorphine discontinuation. Using a recurrent-event, within-person case-crossover approach, we estimated conditional logistic regression models to evaluate the risk of admission for acute SUD-related events and drug-related poisonings between days with and without psychostimulant exposure. Prescription psychostimulants were initiated in 14% (n=143) of pregnant women who were starting buprenorphine for the treatment of OUD. In analyses controlling for insurance status, age, and co-occurring psychiatric conditions and SUDs, psychostimulant receipt was associated with decreased likelihood of buprenorphine discontinuation (adjusted hazard ratio [aHR]: 0.72, 95% CI: 0.66-0.78). While person-days of psychostimulant use was associated with a lower likelihood of emergency admission for SUD-related events (OR: 0.69, 95% CI: 0.63-0.76), we did not observe an association between psychostimulant treatment days and admission for specifically drug-related poisoning (OR: 0.95, 95% CI: 0.70-1.38). The use of psychostimulants in pregnancy may be associated with improved buprenorphine retention as well as decreased acute care utilization for substance use disorder-related events, although other risks of psychostimulant use in pregnant people warrant further investigation. [ABSTRACT FROM AUTHOR]

Select Drug Category Stimulants Topic Treatment Abstract Detail Clinical - Epidemiology Abstract Category Original Research To assess the effect of PAs on OUD buprenorphine treatment retention and or substance use disorder (SUD)-related emergency admission or drug-related poisonings in people with and without a co-occurring PSUD. We used a retrospective cohort design with a secondary analysis of administrative claims data from Merative™ MarketScan® Commercial and Multi-State Medicaid Databases from January 1, 2006, to December 31, 2016. Individuals included were aged 12-64 and had an OUD diagnosis and were prescribed buprenorphine. Our analysis used multivariable Cox regression to evaluate the relationship between PA receipt (predictor variable) and time to buprenorphine discontinuation (outcome variable). The second part of our analysis focused on sub-samples of buprenorphine initiators who had either (1) any SUD-related emergency admissions or (2) drug-related poisoning. These outcomes were modeled as a function of PA exposure using conditional logistic regression models as part of a within-person, case-crossover design. The final sample had 90,269 unique patients with OUD (mean age, 34.2 years [SD=11.3]; 44.2% female; 81.0% non-Hispanic White among Medicaid enrollees) who initiated buprenorphine. Being prescribed a PA was associated with improved buprenorphine retention among individuals both with (aHR, 0.91 [0.86-0.97] and without a concurrent PSUD (aHR, 0.92 [0.90-0.93]). The risk of adverse events associated with PA-treatment days was similar for both individuals with (OR: 0.94 [0.84-1.04] any SUD-related emergency admission; OR: 0.96 [0.75-1.23] drug-related poisoning) and without co-occurring PSUD (OR: 0.82 [0.76-0.88] SUD-related admission; OR: 0.96 [0.84-1.10] drug-related poisoning). PA use was associated with improved buprenorphine retention in people with OUD, both with and without co-occurring PSUD. The risks of SUD-related emergency admissions and drug-related poisonings associated with PA use did not differ between those with and without co-occurring PSUD. [ABSTRACT FROM AUTHOR]

Objective: Persons with opioid use disorder who take benzodiazepines are at high risk for overdose. The objective of this study was to evaluate the association of benzodiazepine and Z-drug use with drug-related poisonings among patients receiving buprenorphine maintenance treatment.Methods: A case-crossover study design was used to analyze prescription claims among persons ages 12-64 with opioid use disorder who had buprenorphine prescriptions and had claims data in the IBM MarketScan databases (2006-2016), encompassing 14,213,075 person-days of observation time for 23,036 individuals who experienced drug-related poisoning. The exposures were buprenorphine prescriptions and benzodiazepine or Z-drug prescriptions, standardized as daily diazepam-equivalent milligram doses and separated by pharmacologic properties (short-acting or long-acting benzodiazepines, Z-drugs). The outcome of interest was nonfatal drug-related poisoning. Conditional logistic regression was used to evaluate variation in benzodiazepine or Z-drug and buprenorphine use between poisoning and nonpoisoning days.Results: Buprenorphine treatment days were associated with a nearly 40% reduction in the risk of poisoning events (odds ratio=0.63, 95% CI=0.60, 0.66) compared with nontreatment days, whereas benzodiazepine or Z-drug treatment days were associated with an 88% increase in the risk of such events (95% CI=1.78, 1.98). In stratified analyses by dose, we observed a 78% (95% CI=1.67, 1.88) and 122% (95% CI=2.03, 2.43) increase in poisonings associated with low-dose and high-dose benzodiazepine or Z-drug treatment days, respectively. High-dose, but not low-dose, benzodiazepine or Z-drug treatment was associated with increased poisonings in combination with buprenorphine cotreatment (odds ratio=1.64, 95% CI=1.39, 1.93), but this was lower than the odds risk associated with benzodiazepine or Z-drug treatment in the absence of buprenorphine (low-dose: odds ratio=1.69, 95% CI=1.60, 1.79; high-dose: odds ratio=2.23, 95% CI=2.04, 2.45).Conclusions: Increased risk of nonfatal drug-related poisoning is associated with benzodiazepine or Z-drug treatment in patients with opioid use disorder, but this risk is partially mitigated by buprenorphine treatment. Dose reduction of benzodiazepines or Z-drugs while maintaining buprenorphine treatment may provide the advantage of lowering drug-related poisoning risk. [ABSTRACT FROM AUTHOR]

Background and Aims: Persons with opioid use disorder (OUD) and co-occurring alcohol use disorder (AUD) are understudied. We identified whether co-occurring AUD was associated with OUD treatment type, compared associations between treatment type and six-month treatment retention and determined whether co-occurring AUD moderated these relationships.Methods: We used an observational cohort study design to analyze insurance claims data from 2011 to 2016 from persons aged 12-64 with an opioid abuse or opioid dependence diagnosis and OUD treatment claim. Our unit of analysis was the treatment episode; we used logistic regression for analyses.Results: Of 211,047 treatment episodes analyzed, 14 % had co-occurring alcohol abuse or dependence diagnoses. Among persons with opioid dependence, persons with co-occurring alcohol dependence were 25 % less likely to receive medication treatment relative to those without AUD. Further, alcohol dependence was associated with decreased likelihood of treatment with buprenorphine (AOR 0.47, 95 % CI 0.44-0.49) or methadone (AOR 0.31, 95 % CI 0.28-0.35) and increased likelihood of treatment with extended-release (AOR 1.36, 95 % CI 1.21-1.54) or oral (AOR 1.73, 95 % CI 1.57-1.90) naltrexone relative to psychosocial treatment. Buprenorphine and methadone were associated with highest retention prevalence regardless of OUD or AUD severity. Co-occurring alcohol abuse or dependence did not meaningfully change retention prevalence associated with buprenorphine or methadone. Co-occurring AUD was not associated with improved retention among persons receiving either formulation of naltrexone.Conclusions: Buprenorphine and methadone are associated with relatively high likelihood of treatment retention among persons opioid and alcohol dependence, but are disproportionately under-prescribed. [ABSTRACT FROM AUTHOR]