Off-Label Use of Lamotrigine and Naltrexone in the Treatment of Ketamine Use Disorder: A Case Report.

Background: Ketamine is a dissociative anesthetic increasingly utilized in United States medical settings for the treatment of mental health conditions. Additionally, it is increasingly used in nonmedical settings for its dissociative properties. While nonmedical ketamine use and ketamine use disorder (KUD) have been observed internationally, KUD, and approaches to its treatment, have not been previously described in the US.

Case presentation: We present the case of a 32-year-old man with KUD who experienced severe cravings despite receipt of residential and intensive outpatient substance use disorder treatment. He resumed use after an initial period of abstinence and was subsequently started on lamotrigine and naltrexone for treatment of depressive symptoms and cravings. This combination altered his experience while on ketamine, resulting in nausea and decreased hallucinogenic effects. In addition, it substantially decreased his cravings, aiding him in achieving longer-term abstinence in combination with receipt of dialectical behavioral therapy, familial support, and involvement in 12-step programming.

Discussion: KUD is a poorly described condition that may become more prevalent as US ketamine use increases. Combining treatment of depressive symptoms and cravings, in this case with lamotrigine and naltrexone, may be a promising pharmacotherapeutic strategy. Lamotrigine, an antiepileptic with glutamate modulating effects, has been utilized to decrease cravings in a variety of substance use disorders. Naltrexone is an opioid antagonist approved for alcohol use disorder and opioid use disorder and is used off-label for stimulant use disorder. This combination offers a possible pharmacotherapeutic option for KUD with more research needed to further evaluate.