Ketamine Treatment for Alcohol Use Disorder

"There is increasing interest in the use of ketamine as an adjunct to treatment of AUD and management of AWS. There were three studies that showed the benefit of using ketamine as an adjunctive treatment to conventional first-line therapies in patients with severe AWS. Ketamine was added to the medication regimen when AWS was refractory to BZD or after clinical signs of delirium tremens (DT). IV ketamine was administered in variable doses ranging from 0.15 to 0.75 mg/kg/h. Ketamine therapy led to a decrease in BZD dose requirements, early resolution of AWS and DT, and decreased duration of ICU stay and intubation time. No AWS complications such as seizures, hallucinations, or delirium tremens were reported after initiation of ketamine (13). The administration of ketamine in AWS was generally safe without any serious adverse effects except oversedation noted in two participants among all the three studies (13, 14). Oversedation was managed by ketamine dose reduction and there was no reported use of any additional treatment modalities. This adverse effect could be explained by either due to the primary known effect of ketamine or due to sedation potentiation by BZD’s administration.

"Despite encouraging results after ketamine initiation in AWS, one of several potential confounders was the use of other medications such as phenobarbital and propofol. In all studies, ketamine was initiated late in AWS management depending on the BZD refractory status of AWS or development of DT. It is possible that the efficacy of ketamine may be greater if it were used as a first line or adjunct to BZD before large doses of BZD or other GABA agonists are used. These limitations make it difficult to determine the true efficacy and situation in which ketamine may be used in AWS.

"We also found seven studies that assessed the efficacy and safety of ketamine for AUD. While the study design, rigor, and target population varied across studies, all studies that examined alcohol outcomes showed greater alcohol abstinence rates in both short-term (21 days) and long-term (1 year) intervals compared to control conditions (43, 44, 46). Ketamine was administered in subanesthetic doses in variable frequency and routes. The highest dose administered was a single dose ketamine 2.5 mg/kg IM (43). Subsequent studies used lower doses – single ketamine 0.35 mg/kg IV infusion, ketamine 0.5 mg/kg IV once weekly for 4 weeks, single ketamine 0.71 mg/kg, three weekly ketamine 0.8 mg/kg IV infusions. Severe adverse effects like euphoria, tachycardia, hypertension, and low mood were reported in 6.3% (3/96) of participants in the Grabski et al. study and affected their normal activities of daily living. Two out of the three participants with severe adverse effects withdrew from the study due to medication intolerability. In addition to ketamine, most studies included adjunctive psychotherapy which may have contributed to outcomes, raising important questions about the frequency, timing, and type of psychotherapy that might help to optimally improve AUD-related outcomes.

"While ketamine did show an improvement in abstinence rates, the longevity of this effect was variable as there was return to alcohol consumption. However, all studies showed ketamine administration produced longer periods of abstinence and reduction in alcohol consumption and cravings, which suggests that ketamine impacts drinking outcomes beyond the direct pharmacologic effects. Furthermore, due to its anti-depressant properties, ketamine may be useful for managing depression that may arise during the abstinence periods."