Since the early 2000s, the
gamma-aminobutyric acid type B (
GABA-B) receptor agonist baclofen has been extensively used for treating
alcohol use disorder (AUD). In some countries, like France, Australia, or Germany,
baclofen has been used at patient-tailored dose regimens, which can reach 300 mgpd or even more in some patients. The
GABA-B-related pharmacology of
baclofen expose patients to a specific profile of neuropsychiatric
adverse drug reactions (ADRs), primarily some frequent
sedative symptoms whose risk of occurrence and severity are both related to the absolute
baclofen dosing and the kinetics of dose variations. Other frequent neuropsychiatric ADRs can occur, i.e.,
tinnitus,
insomnia, or
dizziness. More rarely, other serious ADRs have been reported, like
seizures, manic symptoms, or
sleep apnea. However, real-life AUD patients are also exposed to other
sedative drugs, like alcohol of course, but also
benzodiazepines, other drugs of abuse, or other
sedative medications. Consequently, the occurrence of neuropsychiatric safety issues in these patients is essentially the result of a complex multifactorial exposure, in which
baclofen causality is rarely obvious by itself. As a result, the decision of initiating
baclofen, as well as the daily dose management should be patient-tailored, according the medical history but also the immediate clinical situation of the patient. The overall safety profile of
baclofen, as well as the clinical context in which
baclofen is used, have many similarities with the use of
opiate substitution medications for
opiate use disorder. This empirical statement has many implications on how
baclofen should be managed and dosing should be adjusted. Moreover, this constant patient-tailored adjustment can be difficult to adapt in the design of clinical trials, which may explain inconsistent findings in
baclofen-related literature on AUD.