Ketamine is a dissociative anaesthetic used recreationally for psychomimetic and hallucinogenic effects (Citation1,Citation2). It is an NMDA receptor antagonist (Citation2) and also acts on GABA receptors, with both agonist and antagonist effects (Citation1). Ketamine use disorder is present in ~0.6% of the general population, and risk factors include mood disorders, polysubstance use and adolescence/young adulthood (Citation3). Thus, potential treatments may be effective through targeting both glutamate and GABA receptors. Gabapentin is a GABA analog that reduces glutamate synthesis and facilitates GABA release (Citation4), while topiramate is a nonselective glutamatergic ion channel blocker (Citation5). Both medications are used to treat alcohol use disorder, given alcohol’s propensity to increase central GABA activity and glutamatergic inhibition. We present two cases where combined gabapentin and topiramate were used to successfully treat ketamine use disorder.
Case series
Case 1
Ms A. is a 28-year-old female with schizoaffective disorder, a bipolar subtype who sought treatment for problem ketamine use. She reported smoking ketamine to ease social anxiety, reduce amotivation and anhedonia, and to relieve suicidal ideation. Over the past 5 years, her use has incrementally increased from 0.1 to 3–6 g/day. She was motivated to reduce her use for financial reasons. Gabapentin was started at 100 mg BID and increased to 100 mg TID over one month. This was associated with reduced ketamine use (from ~6 g to <0.25 g/day), cravings and improved mood stability. The dose was further increased to 400 mg TID, with the subsequent addition of topiramate 100 mg HS for persistent ketamine use. She developed bilateral finger paresthesias, which resolved when the dose of topiramate was reduced to 50 mg/day. These effects were sustained after 12 months of maintenance on these agents, and she was able to return to university classes.
Case 2
Mr B is a 35-year-old male with depression, generalized anxiety disorder, and problem use of alcohol and ketamine. He used intranasal ketamine recreationally(1–2 g/day), with reported symptoms of anxiety and dissociation. He was prescribed naltrexone 50 mg daily to reduce alcohol cravings but experienced severe gastrointestinal side effects. Subsequently, gabapentin was started at 600 mg at bedtime for one week; however, the patient experienced excessive daytime somnolence. Gabapentin was reduced to 200 mg twice daily, which he tolerated, and later increased to 300 mg TID to combat persistent ketamine cravings and anxiety. His ketamine use was significantly reduced (<1 g/day), and he was able to achieve complete abstinence from alcohol. Topiramate (25 mg at bedtime) was started, which resulted in a further reduction in ketamine use (<0.5 g/day), reduced cravings and improved mood stability. Further increases of topiramate to 100 mg qHS (without any reported side effects) over the next month led to a further reduction in cravings, and ketamine use was limited to weekends.
Discussion
We describe two cases of combined treatment with gabapentin and topiramate, which led to reduced ketamine use, cravings and improved mood. Neither of these patients received any psychotherapy to address their ketamine use. Mechanisms behind these clinical effects are unclear. In alcohol use disorder, gabapentin reduces alcohol consumption and cravings and increases abstinence rates (Citation6,Citation7). Similarly, topiramate reduces alcohol cravings and heavy alcohol use (Citation5), and this combination appeared to be well-tolerated. A limitation was the lack of urine toxicology data.
We suggest that the combination of gabapentin and topiramate ameliorates GABAergic and glutamatergic dysfunction associated with ketamine use disorder (Citation8). Both medications were used at sub-therapeutic doses, and thus it is not known if these results would have been sustained if either drug was used alone at therapeutic doses. Nonetheless, our observations merit further investigation in larger samples using controlled clinical trials to determine the potential efficacy of ketamine use disorder.
Disclosure statement
No potential conflict of interest was reported by the author(s).
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References
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