To the Editors
Pregabalin is a gamma-aminobutyric acid analog that is approved for the treatment of epilepsy, neuropathic pain, and generalized anxiety disorder. However, it has been anecdotally reported from the United States,1 Germany,2 Sweden,3 and Norway4 that the molecule may possess a potential of misuse. Pregabalin is widely described online by users as an “ideal psychotropic drug” for recreational purposes.5 In line with this, pregabalin has recently been included in the list of new recreational psychoactive substances officially notified to the relevant European Union agencies.6 We present here the first 2 cases of pregabalin misuse identified in southern Europe; they highlight a few related concerns, including intake of large dosages, allegations of drug smoking, and possible occurrence of myositis.
Patient 1, a 32-year-old white European, was referred to the local National Health Service outpatient drug treatment unit for issues related to pregabalin misuse. The case patient had a previous diagnosis of antisocial personality disorder and reported a history of benzodiazepines, cocaine, and ecstasy abuse. Because of a diagnosis of a neuropathic pain condition, his general practitioner started him on a pregabalin daily dosage of 75 mg 2 times a day (BD), which was then increased to 150 mg BD by day 5 and to 300 mg BD by day 12. Roughly over the following 4 weeks, however, the patient gradually increased the dosage up to an alleged daily amount of 4500 mg. He managed to get access to these levels of pregabalin tablets either through a new general practitioner’s prescription or obtaining it from a friend. At the same time, he was misusing with both alcohol and cannabis. On a few occasions, he tried to discontinue his pregabalin intake, but as a result was feeling anxious, extremely irritable, and aggressive. Conversely, in association with his pregabalin intake, he was feeling more relaxed, “more empathetic,” and with “very good drive.” He was describing his life before pregabalin initiation as “extremely boring” and characterized by constant feelings of anger. At admission, the urine toxicology specimen was positive only for cannabis. The pregabalin dosage was gradually reduced, and benzodiazepines were introduced to control the case patient’s withdrawal signs and symptoms. However, after a few days, the patient dropped out of treatment.
Patient 2, a 33-year-old white European, was referred to the local National Health Service outpatient psychiatric unit for issues related to both his bipolar and generalized anxiety disorder conditions. Because of these, he was prescribed olanzapine, 10 mg/d, and was started with pregabalin, 75 mg once a day. Pregabalin was then increased to 75 mg BD by day 3 and to 150 mg BD by day 8. Up to 5 years before, he was misusing with ecstasy and alcohol. At admission, his urine toxicology specimen was positive for cannabis only. Over the first few days of pregabalin intake, he was feeling increasingly relaxed, emphasizing that the pregabalin effects were “very similar to those of cannabis.” As a result, over the first 4 weeks or so, he gradually increased the dosage up to 1500 mg, feeling as being “under the influence of an anesthetic,” and “very light.” To achieve both a quicker and more intense effect, he also tried to smoke the crushed pregabalin tablets. He allegedly obtained the extra pregabalin tablets from a friend. Over time, however, he developed an intense muscle pain, as he had “severely torn his leg muscle.” Although unfortunately, CPK levels were not made available, a tentative diagnosis of myositis was made, with causes different from pregabalin intake having been ruled out by both clinical interview and full medication review. The Naranjo Probability Scale7 indicated a probable relationship between pregabalin intake and the onset of myositis. Pregabalin was gradually discontinued, and benzodiazepines were introduced to control the observed increase in both anxiety and craving levels. The muscular pain disappeared over a week.
The case reports here described suggest that pregabalin experimenters might be profiled as individuals with a history of recreational polydrug, including ecstasy, misuse and, as such, confirming previous observations.5 Pregabalin dosages reported here, especially in case 1, were clearly a reason of concern and certainly in excess of the advised daily maximum level (eg, 600 mg).8 Overall, the misuse of pregabalin mostly seem to occur orally, but intravenous, rectal (“plugging”), and “parachuting” (emptying the content of the capsule into a pouch) self-administration techniques have been described as well.5 However, patient 2 allegedly tried to smoke an unconfirmed amount of pregabalin crushed tablets, a technique, which to the best of our understanding, had never been reported before.
In both cases, the patients were started with pregabalin for medical reasons. However, because of the rapid development of high tolerance levels,5 increasing dosages were eventually self-administered. In both cases, the abrupt/rapid discontinuation of pregabalin was associated with withdrawal signs and symptoms, suggesting the potential of physical dependence.9
A possible myositis episode, considered as probably associated with the pregabalin intake, was identified in case 2. Although pregabalin has only rarely been associated with myositis/rhabdomyolysis,8 its occurrence might have been facilitated here by the unusually high dosages ingested. The muscular syndrome did however occur in association also with the cannabis discontinuation, making the interpretation of the clinical observation even more difficult.
Both cases seem to suggest the pregabalin potential for diversion, which may be an issue of particular concern. In fact, a range of prescription drugs (including pregabalin)5 may be widely accessible through online pharmacies.10,11
One could argue that pregabalin, different from benzodiazepines,5 may possess both a sedative and a cannabinoid-like effect, as described in case 2. However, pregabalin effects on both patients were here confounded by their concomitant cannabis use; and hence, only further observations may shed more light on this issue.
Although the precise mechanism of action of pregabalin is still unclear,12 the drug has recently been proposed as a treatment for both alcohol13 and benzodiazepine14 dependence. The dosages prescribed in these 2 cases (ie, 600 and 300 mg/d) were quite high. Furthermore, the patients had been exposed to this prescribing dosage after a fairly rapid titration process, albeit within the time limit advised.8 One cannot exclude that these issues could have been somewhat associated with the development of craving. In fact, in those recent trials in which the pregabalin dosage was more gradually increased, no addiction potential was actually identified.15–17 Finally, one could wonder if these patients, who eventually further escalated their intake to reach extremely large dosages in a fairly short period of time, were indeed actively seeking to experience the psychoactive effects here described, as often is the case with drug misusers. As with any other drug, physicians should carefully evaluate patients for a history of drug abuse and observe them for signs of pregabalin misuse.2
Dario Carrus, MD
Department of Mental Health
Fabrizio Schifano, MD, MRCPsych
University of Hertfordshire
School of Life and Medical Sciences
The present study was carried out with the partial support of the European Commission (EC) for both the Psychonaut Web Mapping System (A/800102; 2006 348) and the ReDNet (EC Executive Agency for Health and Consumers in the framework of the Public Health Programme; 2009 12 26) projects. The views expressed here reflect only the authors’ views and not necessarily those of the relevant EC officers.
AUTHOR DISCLOSURE INFORMATION
The authors declare no conflicts of interest.
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