A survey of drug liking and cravings in patients using sublingual or intranasal ketamine for treatment resistant depression: A preliminary evaluation of real world addictive potential

Abstract

Ketamine has gained rapid popularity as a treatment option for treatment resistant depression (TRD). Though seen only in limited contexts, ketamine is a potential drug of abuse, addiction and diversion. Clinical ketamine studies to date have not systematically evaluated factors relevant to addiction risk in patients with TRD, but in treating patients with ketamine, risks of potential harms related to addiction must be considered. As clinical access to intravenous ketamine programs is limited in much of Canada, these considerations become even more important for clinicians who elect to offer patients less supervised, non-parenteral forms of ketamine treatment. This study explores factors relevant to addiction risk in a real-world sample of 33 patients with TRD currently or previously treated with sublingual (SL) or intranasal (IN) ketamine in the community. First, patients were surveyed using a Drug Liking and Craving Questionnaire (DLCQ) to assess their level of drug liking and craving for ketamine, and to screen for symptoms of a ketamine use disorder. Second, the pharmacy records of these patients were reviewed for red flags for addiction such as dose escalation or early refills. Third, surveys were administered to the treating psychiatrists of patients who had discontinued ketamine to determine if abuse concerns contributed to reason for discontinuation. Though limited to a small sample, results indicate that ketamine is not a universally liked or craved substance in patients with TRD. Prescribers of non-parenteral ketamine should monitor patients and prescribe cautiously. Factors related to addiction (as in the DLCQ) should be explored for clinicians to consider individual risk/benefit for judicious use of ketamine in patients with TRD.

Facts and myths about use of esketamine for treatment-resistant depression: a narrative clinical review

“…( 93 ) developed a visual analog scale for assessing esketamine craving and drug likeability, intended as a predictor of potential addition ( 94 ). The risk of esketamine addiction does not affect all patients equally ( 95 ). Moreover, slow de-tritation of esketamine and combined use of bupropion were suggested for managing drug-seeking and craving behaviors ( 34 ).…”

“…Although a causal role of dissociation in improving depressive symptoms could be hypothesized, Ballard and Zarate ( 87 ) showed that it is not necessary to determine antidepressant effects of ketamine and derived medication. Moreover, the potential addiction from this drug resulted to involve patients treated with esketamine ( 95 ).…”

Beyond therapeutic potential: a systematic investigation of ketamine misuse in patients with depressive disorders

“…Chronic ketamine abuse has been linked to structural alterations in the brain, including reductions in gray matter volume and disruptions in neural connectivity [ 17 ]. Studies have reported significant brain atrophy and neurological dysfunction in individuals with a history of prolonged ketamine misuse, highlighting the need for caution and vigilance in its use [ 40 ].…”

Use of ketamine for treatment resistant depression: updated review of literature and practical applications to a community ketamine program in Edmonton, Alberta, Canada

“…Drug-liking, was variable, with a number of patients indicating a dislike for the dissociative effects of ketamine. Overall risk level appeared low, but not negligible ( 81 ). Similarly, there is only one case report of drug seeking behavior and craving in a single patient treated with esketamine ( 82 ).…”

“…A recent chart review of a sample of patients from our program found SL ketamine was generally started at 50-200 mg, though the most common starting doses were 100 mg and 150 mg. Subsequent increases went as high as 300 mg ( 81 ). IN ketamine was typically started at 100 mg and increased as high as 150 mg.…”