Adverse Effects Are Frequent and Mostly Persistent with High-Dose Baclofen

High-dose baclofen to treat alcohol use disorder (AUD) has been the subject of intense debate in France, and some physicians have prescribed as “compassionate use.” The efficacy of high-dose baclofen for treating AUD is still unknown, especially when the treatment is introduced while patients are still drinking heavy amounts. Investigators conducted a retrospective case series of patients who received high-dose (> 90mg in a day) baclofen from a single general practitioner to establish the tolerability of the treatment. Baclofen was prescribed to patients with heavy drinking (> 60 g ethanol in a day for men, > 40 g for women). The dose was increased until the patients reached low-risk drinking (40 g ethanol in a day for men, ≤ 20 g for women,) or abstinence. Of 146 patients who received baclofen (75% met DSM-IV criteria for alcohol dependence), 116 (79%) were interviewed.

• 78% reported at least 1 adverse effect.
• The mean (SD) number of adverse effects per patient was 2.8 (2.7).
• 53% reported persistent adverse effects.
• The most frequent adverse effects were: somnolence (40%); insomnia (20%); asthenia, paresthesia, and respiratory disorders (17%); headaches (13%); sweating and nausea (10%); memory lapses, tinnitus, reduced libido, and hypomania (7%).
• The mean dose at which the first adverse effect appeared was 83 (57) mg in a day.

Comments:

Despite important limitations that could lead to an underreporting of adverse effects and the impossibility by design to conclude whether or not they are attributable to baclofen (retrospective design, lack of control, risk of recall bias, interviews conducted by the prescribing physician in most cases), this study shows that high-dose baclofen’s adverse effects are very frequent, persistent in most cases, and serious in some (e.g. hypomanic episodes). Given the frequency of adverse effects and their associated risks, evidence of efficacy is necessary to justify high-dose baclofen prescription for people with an alcohol use disorder who are drinking heavy amounts. 

Nicolas Bertholet, MD, MSc

Reference:

Rigal L, Legay Hoang L, Alexandre-Dubroeucq C, et al. Tolerability of high-dose baclofen in the treatment of patients with alcohol disorders: a retrospective study. Alcohol Alcohol. 2015;50(5):551–557.