IMPORTANCE Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality.OBJECTIVE To estimate the association of time receiving OAT with mortality.DATA SOURCES The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews.STUDY SELECTION All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included. DATA EXTRACTION AND SYNTHESISThis systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses. MAIN OUTCOMES AND MEASURESOverall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. RESULTSFifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI,, remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56). CONCLUSIONS AND RELEVANCEThis systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains ...

Aims: The aim of this study was to assess the use and factors associated with the misuse of gabapentin and pregabalin in the general French population, through a cohort study in the EGB (General Sample of Beneficiaries), a national representative sample of the French general population.Methods: New users of gabapentin and pregabalin were identified from June 2006 to December 2014, and new users of duloxetine served as control group. Misuse was defined as a use of higher daily doses than recommended. Cox proportional hazard regression models were performed to identify associated factors of misuse.Results: Misuse was more frequent in the 8692 new users of pregabalin (12.8%) than in the 1963 gabapentin (6.6%) or the 3214 duloxetine new users (9.7%) (P < 0.001). Factors associated with misuse were pregabalin (hazard ratio [HR] 1.48; 95% confidence interval [CI] [1.29-1.69]), age (HR [18-45] versus > 70 years 1.98 [1.70-2.31] and HR [58-70] versus > 70 years 1.25 [1.06-1.47]), multiple prescribers (HR 2 or 3 versus 1 prescriber 1.29 [1.15-1.45]; HR 4 or more versus 1 prescriber 1.54 [1.30-1.83]), cancer (1.28 [1.11-1.47]), multiple sclerosis (1.53 [1.07-2.18]), neuropathy (1.85 [1.19-2.89]), depression (1.26 [1.07-1.49]) and methadone (2.61 [1. 16-5.84]). After this first episode of drug misuse, 11.6% of gabapentin and 10.7% of pregabalin misusers developed a primary addiction.Conclusion: In a cohort of new users, misuse is more likely to occur in new users of pregabalin, with different associated factors of misuse compared to gabapentin and duloxetine. Health professionals and prescribers must be aware of this misuse potential, which could lead to abuse and dependence.

In this study, we aimed to provide an updated overview of drug data contained in the French health insurance database (SNIIRAM) and its associated national representative sample (EGB). This study identified most common problems concerning drug data: (i) change in level of coverage of drugs of interest (drug no more eligible for reimbursement or no more prescription-only), (ii) break in patients' eligibility (in connection with change of healthcare plan or patients' identifier), and (iii) technical and regulatory issues. We provide a brief checklist to enable a structured identification of these issues. The impact of gap in drug data availability on study validity will depend on the research question, drug, setting, and population of interest. The French health insurance database and associated sample are valuable resources for pharmacoepidemiological research. There is a need to pursue further methodological and validation studies to promote accurate and transparent use of French health insurance databases for pharmacoepidemiology.

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In France, most cases of opioid use disorder are treated with buprenorphine by general practitioners in private practice. Using reimbursement data of a representative sample of the French population, Echantillon Généraliste des Bénéficiaires, we investigated mortality during periods when patients were in and out of treatment in a cohort of 713 new users of buprenorphine having a mean (SD) followup of 4.5 (1.5) years. The mortality rate was 0.63 per 100 person-years (95% CI, 0.40-0.85) overall. In a multivariate Cox regression model, compared with being in treatment, being out of treatment was associated with a markedly increased risk of death (hazard ratio = 29.04; 95% CI,). Buprenorphine appears to be a strong protective factor against mortality.

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The first cases of pregabalin-related abuse or dependence reported in France occurred later than in other European countries, since none had been described before 2010. This analysis in the FPVD did not find a higher proportion of abuse/dependence with pregabalin in comparison with other drugs. Considering evidence of pregabalin abuse worldwide, this analysis underlines the limitations of spontaneous reporting system in the field of addictovigilance.

This study highlights the need to take account of the impact of unobservable exposure periods on risk estimates. Copyright © 2017 John Wiley & Sons, Ltd.