ZOLPIDEM: INTRAVENOUS MISUSE IN DRUG ABUSERS

Abstract

Zolpidem, a short-acting imidazopyridine, has been used for over a decade in more than 100 countries for the short-term treatment of insomnia. Epidemiological studies indicate a remarkably low incidence of zolpidem abuse compared to benzodiazepines used to treat sleep disorders [1]. Cases that do occur typically involve patients with a history of abusing other drugs [1–3]. As far as we know, only two cases of zolpidem intravenous injection have been reported, both involving drug addicts [4, 5]. In a re-examination of our own data on psychoactive drug consumption [6], we found only seven reports of zolpidem injection amongst 460 patients who visited a drug addiction center in northern France. The number of zolpidem injectors could be underestimated, however, simply because clinicians do not explicitly question drug addicts about it. We therefore carried out a survey to determine the prevalence and geographical extent of zolpidem intravenous misuse in France. Specific questionnaires about drug and zolpidem injection were given to patients who visited one of five drug addiction centres throughout France over a 3-month period. Surprisingly, only three new cases of zolpidem injection were identified out of 733 patients interviewed. The lifetime prevalence of intravenous misuse was thus 0.41%[0.09–1.19] 95% CI in our sample and 0.72%[0.15–2.10] 95% CI among the 414 injecting drug users. The association of dependence (benzodiazepines, drugs or alcohol) or other psychiatric disorders with zolpidem abuse [1–3] was confirmed. All three zolpidem injectors were opiate-dependent men, aged 28, 24 and 35 years old, who had abused multiple substances for 2–12 years, mainly intravenously. All were on methadone treatment at the time of the survey. Two of these patients had previously used oral benzodiazepines for non-medical purposes (flunitrazepam, diazepam, alprazolam); one of the two had injected flunitrazepam. One subject had a history of other psychiatric disorders, another abused alcohol. All had been prescribed zolpidem for the treatment of insomnia, at the age of 18, 21 and 32 years. The first injection of zolpidem occurred 8 years after initial use for the first subject and within one year for the other two. Reasons for zolpidem injection were different: compulsive-like injecting behavior independent of the specific drug, relieving the down feeling following cocaine use, and seeking reinforcing effects. Zolpidem does not appear to be highly addictive or attractive as a recreational drug. Only one of our subjects was continuing to inject zolpidem at the time of the survey, having done so more than 50 times, typically after cocaine use. The other two injected zolpidem less than 10 times overall and stopped such misuse more than one year before the survey. Only one of the three reported injecting zolpidem for recreational purposes. Selectivity of zolpidem for the alpha 1 subtype of benzodiazepine receptors, which mediates sleep induction, means that other pharmacological effects (including euphoria and reduced anxiety) produced by other subtypes will not be seen at low doses. Abuse of high doses would be unlikely because of a strong sedation. Furthermore, although the survey was conducted in centres across France, all three cases came from a single region in the north. Considering the wide use of zolpidem in the treatment of sleep disorders and the penchant of drug addicts to misuse psychotropic drugs for recreational purposes, the limited spread of zolpidem intravenous misuse means that it is unlikely to possess strong reinforcing properties. Sleep disorders are frequently observed in opiate-dependent patients receiving drug maintenance therapy. The reassuringly low prevalence of zolpidem intravenous misuse among these patients indicates a low susceptibility for misuse. Physicians should nevertheless be cautious when prescribing zolpidem to patients with a history of substance abuse, especially those with a history of injecting behavior.