This study highlights the importance of assessment for PD and AUD in OUD patients in order to identify individuals at substantially elevated mortality risk to enable a more personalized approach to their medical care.

Aims To investigate clustering of all-cause and overdose deaths after a transfer of patients and their care to alternative treatment provider and after the end of opioid substitution therapy (OST) in opioid-dependent individuals in specialist addiction treatment. Design, Setting and Participants Mortality data were identified within a sample of 5335 patients with opioid use disorder who had received OST treatment between 1 April 2008 and 31 December 2013 from a large mental health-care provider in the United Kingdom. We investigated the circumstances and distribution of the 332 deaths identified within the observation window with a specific focus on overdose deaths (n = 103) after a planned discharge, dropout and transfer between services. Measurements Crude mortality rates for overdose mortality 14 days, 28 days and more than 1 month after the end of treatment/transfer for overdose mortality. Findings Of 47 individuals who died from overdose after having been transferred between services, nine died during the first 2 weeks [crude mortality rate (CMR) = 136.4, 95% confidence interval (CI) = 64.3-243.1] and a further five died during the first month posttransfer (CMR= 79.5, 95% CI = 44.2-129.7). Of the 32 individuals who died from overdose after planned OST cessation, five died during the first 2 weeks (CMR = 151.5, 95% CI = 51.1-319.0) and a further four died during the first month postdischarge (CMR = 82.6, 95% CI = 38.4-151.0). Conclusions In the United Kingdom, opioid-dependent people who are transferred to an alternative treatment provider for continuation of their opioid substitution therapy experience high overdose mortality rates, with substantially higher rates during the first month (especially during the first 14 days) following transfer.

Aims: To test the safety of new buprenorphine oral lyophilisate wafer (“bup-lyo”) versus standard sub-lingual buprenorphine (“bup-SL”). Design: Randomised (2:1) open-label study; opioid-dependent subjects; subsequent partial cross-over. Settings: Specialised clinical trials facility and addictions treatment facility. Participants: Opioid-dependent subjects (n = 36) commencing buprenorphine maintenance (personalised dose-titration) including patients co-using alcohol, cocaine and benzodiazepines (below thresholds). Measurements: Respiratory function (respiratory rate, pulse-oximetry); medication hold and dose adequacy; opiate withdrawal signs and symptoms; tablet disintegration times; treatment retention. Pharmacokinetics (PK) for plasma buprenorphine and norbuprenorphine (n = 11). Findings: Oral lyophilised buprenorphine (“bup-lyo”) completely dissolved within 2 min for 58 vs. 5% for “bup-SL.” Dose titration resulted in similar maintenance dosing (10.8 vs. 9.6 mg). There were no significant between-group differences in opiate-withdrawal phenomena, craving, adequacy of “hold,” respiratory function. No serious adverse events (AEs), nor “severe” AEs, although more AEs and Treatment-Emergent AEs with “bup-lyo” (mostly “mild”). PK found greater bioavailability of buprenorphine with “bup-lyo” (but not norbuprenorphine). Conclusions: Orally disintegrating buprenorphine oral lyophilisate wafer disintegrated rapidly. No increased respiratory depression was found and clinically no difference between medications was observed. PK found substantially increased bioavailability of buprenorphine (but not of nor-buprenorphine) with “bup-lyo” relative to “bup-SL.” In supervised dosing contexts, rapidly disintegrating formulations may enable wider buprenorphine prescribing.

Exploratory investigation found respiratory depression more strongly associated with norbuprenorphine than with buprenorphine. This accords with animal studies.
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