Nalmefene, Given as Needed, in the Routine Treatment of Patients with Alcohol Dependence: An Interventional, Open-Label Study in Primary Care

Abstract

Aims: This 12-week, open-label, primary care study (NCT02195817) evaluated the efficacy and safety of nalmefene, taken as needed, to reduce alcohol consumption in adults with a diagnosis of alcohol dependence and drinking at least at high drinking risk levels (DRL, > 60 g/day for men, > 40 g/day for women). Methods: Following the Screening Visit, patients recorded their daily alcohol consumption for 2 weeks. Patients were then categorised by their self-reported drinking levels; those who maintained at least a high DRL in the 2-week period were included in Cohort-A, and those who reduced their alcohol consumption below high DRL were included in Cohort-B. Cohort-A received simple psychosocial interventions and were supplied with nalmefene 18 mg to be taken on days when they perceived a risk of drinking alcohol. Patients in Cohort-B received a simple psychosocial intervention and were treated per normal practice. Results: Of the 378 enrolled patients, 330 were included in Cohort-A and 48 in Cohort-B. For patients in Cohort-A, the mean change from screening to Week-12 in the number of heavy drinking days/month was –13.1 days/month (95% CI –14.4 to –11.9, p < 0.0001). Overall, 55% of patients reduced their DRL by ≥2 risk levels and 44% of patients reduced to a low DRL. The most common adverse events were nausea (18.3%) and dizziness (17.7%). Patients in Cohort-B maintained their lower level alcohol consumption at the 12-week follow-up. Conclusions: Patients with alcohol dependence treated in primary care with nalmefene, taken as needed, in conjunction with simple psychosocial support, significantly reduced their alcohol consumption. Treatment was well tolerated.

The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies

“…Compared with naloxone, nalmefene has been shown to have superior efficacy in reversing the carfentanil-induced loss of righting reflex and respiratory depression in rats 132 . Nalmefene is generally well tolerated and is a recent option for patients with alcohol dependence 133–135 . Additionally, novel, selective, and potent μ-opioid receptor antagonists, such as 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ) and 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(indole-7-carboxamido)morphinan (NAN), have been reported to produce less opioid tolerance, dependence, and withdrawal signs.…”

Neuroimaging of inflammation in alcohol use disorder: a review

“…Finally, TLR4 inhibitors such as nalmefene and naltrexone have also been useful for decreasing alcohol administration in rodents [203,204]. In humans, these medications have generally found success in reducing alcohol consumption [205][206][207]. Given the link between gray matter integrity and TLR4 [190,191], these drugs might also protect against cognitive impairments linked to gray matter reduction [208,209].…”

Safety of nalmefene for the treatment of alcohol use disorder: an update

“…Four studies have been conducted in specialized treatment units (n=110) [41,42], primary care settings(n=330) [43] and in psychiatric outpatients (n=65, n=25) [44,45]. They were singlearm/naturalistic [41,42,44] or open-label studies [43] with follow-ups ranging from eight weeks to six months. In these studies it was found that nalmefene decreased HDD and TAC, and improved secondary outcomes, including reduction in daily alcohol consumption of at least 70%, a downshift of two categories in the DRL (WHO), a shift to the LR category, Borderline…”

“…Results from the multicenter open-label study by Castera et al (2019)[43], point out that nalmefene was well tolerated. From the 330 patients included, 19 (6.4%) withdrew from the study due to adverse events (mainly nausea and dizziness).…”