Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence

Abstract

Alcohol use disorders (AUD) cause significant morbidity and mortality worldwide, but pharmacological treatments for them are underused, despite evidence of efficacy.Acamprosate, naltrexone, nalmefene and disulfiram are all approved in one or more region for the treatment of alcohol use disorders. Baclofen currently has a temporary indication in France. Safety considerations for using psychopharmacological treatments in this patient group include the impact of concurrent alcohol consumption at high levels, multiple physical comorbidities which may interfere with pharmacological effects, distribution and metabolism, and concomitant medication for the treatment of comorbid physical and psychiatric conditions. The five drugs, including an extended-release injectable suspension of naltrexone, have different safety profiles which need to be balanced with the objective of treatment (initiation or continuation of abstinence, or reduction of drinking), individual patient preferences and comorbid conditions. Appropriate treatment will be based on the unique riskbenefit profile in each case. KEY POINTS Acamprosate has an excellent safety profile and is recommended as first line treatment for patients wishing abstinence. Naltrexone and nalmefene are contraindicated with opioid-containing medication, but have reasonable tolerability  The disulfiram-alcohol reaction is integral to its use, but careful patient selection and monitoring can mitigate safety risks  Baclofen is a CNS depressant so there are potential concerns regarding overdose: it may have a role in patients with severe liver disease Pharmacological treatments for alcohol dependence 3

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

“…There is limited evidence for their use in patients with comorbid schizophrenia, but the principle of active treatment of alcohol dependence as part of the overall patient management plan is key (Lingford-Hughes et al, 2012). Data relating to the pharmacokinetics of these medications as well as safety data can be used to extrapolate from the treatment of alcohol dependence alone to help determine the risk-benefit profile of treatment with a specific medication for an individual patient (Sinclair et al, 2016).…”

Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol‐Preferring (P) Rats

“…Of these, naltrexone and acamprosate are the most widely used (O'Malley and Froehlich, ). Several reviews and meta‐analyses have reported that these drugs are only moderately effective for treating alcohol relapse because relapse rates of 83 to 86% are reported in individuals treated with acamprosate (Donoghue et al., ; Pilling et al., ; Rösner et al., ; Sinclair et al., ) and relapse rates of 83 to 92% are reported in individuals treated with naltrexone (Donoghue et al., ; Pilling et al., ; Sinclair et al., ). Identifying new medications for the treatment of AUD is of prime importance.…”

Reduction in Drinking was Associated With Improved Clinical Outcomes in Women With HIV Infection and Unhealthy Alcohol Use: Results From a Randomized Clinical Trial of Oral Naltrexone Versus Placebo

“…Overall, the drinking results are similar to those of other studies comparing naltrexone to placebo, which tend to demonstrate mild or modest improvements for naltrexone when compared to placebo (Canidate et al., ; Kranzler and Soyka, ). However, these modest improvements should be balanced by a relatively high number of persons who experience side effects such as nausea and vomiting (Sinclair et al., ). The fact that 94% of study participants were African American is different from most previous alcohol trials.…”