Abuse of psychiatric medications: Not just stimulants and benzodiazepines

Unlike bupropion, quetiapine’s dopamine antagonism makes it unlikely to be a truly addictive drug, although this mechanism of action could mediate an increase in concurrent psychostimulant use.⁸³ A few case reports have described a quetiapine discontinuation syndrome similar to that of antidepressants,^60,65,84-88 but withdrawal symptoms suggestive of physiologic dependence may be mediated by non-dopaminergic effects through histamine and serotonin receptors.^84,89 Evidence for quetiapine misuse being associated with craving and compulsive use is lacking, and true quetiapine addiction is probably rare.

Similar to bupropion, preliminary findings have suggested promise for quetiapine as a putative therapy for other SUDs.^90-93 However, subsequent RCTs have failed to demonstrate a therapeutic effect for alcohol and cocaine use disorders.^94-96 Given these negative results and the clear M/A potential of quetiapine, off-label use of quetiapine for the treatment of SUDs and psychiatric symptoms among those with SUDs must be considered judiciously, with an eye towards possible diversion and avoiding the substitution of one drug of abuse for another.

Gabapentinoids

In 1997, the first published case report of gabapentin M/A described a woman who self-administered her husband’s gabapentin to reduce cravings for and withdrawal from cocaine.⁹⁷ The authors highlighted the possible therapeutic benefit of gabapentin in this regard rather than raising concerns about diversion and M/A. By 2004, however, reports of recreational gabapentin M/A emerged among inmates incarcerated within Florida correctional facilities who self-administered intranasal gabapentin to achieve a “high” that was “reminiscent of prior effects from intranasal ingestion of cocaine powder.”⁹⁸ In 2007, a single case of gabapentin misuse up to 7,200 mg/d (recommended dosing is ≤3,600 mg/d) was reported, with documentation of both tolerance and withdrawal symptoms.⁹⁹ As of 2017, a total of 36 cases of gabapentin M/A and 19 cases of pregabalin M/A have been published.¹⁰⁰

In the past decade, anecdotal reports have given way to larger-scale epidemiologic data painting a clear picture of the now-widespread M/A of gabapentin and other gabapentinoids. For example, a study of online descriptions of gabapentin and pregabalin M/A from 2008 to 2010 documented:

• oral and IM use (gabapentin)
• IV and rectal (“plugging”) use (pregabalin)
• “parachuting” (emptying the contents of capsules for a larger dose) (pregabalin)
• euphoric, entactogenic, stimulant, calming/anxiolytic, and dissociative subjective effects (gabapentin/pregabalin)
• rapid development of tolerance to euphoric effects leading to self-administration of increasing doses (gabapentin/pregabalin)
• frequent co-administration with other drugs of abuse, including alcohol, benzodiazepines, cannabis, stimulants, opiates, hallucinogens, gamma-hydroxybutyrate, mephedrone, and Salvia divinorum (gabapentin/pregabalin)¹⁰¹

Several systematic reviews of both anecdotal reports and epidemiologic studies published in the past few years provide additional evidence of the above, such as:

• excessive dosing with self-administration
• intranasal and inhaled routes of administration
• diversion and “street value”
• greater M/A potential of pregabalin than gabapentin
• the presence of gabapentinoids in postmortem toxicology analyses, suggesting a role in overdose fatalities when combined with other drugs.^100,102,103

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