Pregabalin poisoning and rising recreational use: a retrospective observational series

Abstract

With rising use worldwide, pregabalin is increasingly implicated in poisoning deaths. We aimed to investigate the clinical effects and complications of pregabalin poisoning. Methods: This is a retrospective review of patients presenting with pregabalin poisoning to two tertiary toxicology units from 1 July 2014 to 30 June 2019. Patients were identified from prospective databases maintained by both units and data were extracted from these in addition to medical records. Results: There were 488 presentations in 413 patients (237 [57%] male) over the five-year period. The median age was 41 years (IQR 31-50 years). Deliberate selfpoisonings accounted for 342 (70%) presentations, with 121 (25%) recreational exposures. Recreational exposures increased over the period from 2 (4%) in the first year to 54 (39%) presentations in the final year. The median dose of pregabalin was 1200 mg (IQR 600-3000 mg, range 75-16 800 mg). Co-ingestions occurred in 427 (88%) presentations, with sedating agents being co-ingested in 387 (79%)-most commonly opioids and benzodiazepines in 201 (41%) and 174 (36%) presentations respectively. Coma (GCS < 9) occurred in 89 (18%) cases, with 52 (11%) patients being intubated. Only one (0.2%) of these patients had not co-ingested a sedating agent. Hypotension occurred in 26 (5%) cases, all with co-ingestants. Seizures occurred in 11 (2%) cases, 3/59 (5%) in pregabalin-only overdoses. The median length of stay was 16.5 hours (IQR 10-25 hours). Conclusions: Pregabalin overdose does not cause severe toxicity, but rather mild sedation and, uncommonly, seizures. Coma is common in the presence of sedating co-ingestants. Recreational use is increasing. K E Y W O R D S drug abuse, overdose and poisoning, toxicology 1 | INTRODUCTION Pregabalin is a gamma-aminobutyric acid analogue that binds to voltage-gated calcium channels to inhibit the release of excitatory neurotransmitters, which accounts for its antinociceptive, anticonvulsant and anxiolytic properties. 1,2 Over the last decade, pregabalin has been increasingly prescribed for neuropathic pain, as well as a number of off-label indications including anxiety, mood instability and withdrawal syndromes. 1-4 With the broadening of both approved and off-label indications, pregabalin use has increased worldwide over the last The authors confirm that the PI for this paper is Katherine Isoardi and that she had direct clinical responsibility for patients.

Clinical correlates and outcomes associated with pregabalin use among people prescribed opioids for chronic non‐cancer pain: A five‐year prospective cohort study

“…Population-level studies show increased harms related to pregabalin use over time, though harms are often reported among young people using pregabalin nonmedically. 27,28,43,52 Nonetheless, the combined use of pregabalin with other sedative medicines is of concern because of the potential for medicine interactions and increased side effects in older adults.…”

“…While understandable, this is of concern given local 43 and international 27 evidence of overdoses occurring when gabapentinoids are used in combination with opioids, in addition to concerns relating to other adverse effects including effects on cognition. Population‐level studies show increased harms related to pregabalin use over time, though harms are often reported among young people using pregabalin nonmedically 27,28,43,52 . Nonetheless, the combined use of pregabalin with other sedative medicines is of concern because of the potential for medicine interactions and increased side effects in older adults.…”

Pregabalin prescribing patterns in Australian general practice, 2012–2018: a cross-sectional study

“… 8 – 10 When pregabalin is taken in combination with other medicines with sedative properties, particularly opioids and benzodiazepines, it can lead to central nervous system depression, with the greatest risk observed with high doses. 11 In Australia, pregabalin recreational use, poisonings, and deaths have all been increasing, 5 , 11 with a tenfold increase in pregabalin misuse-related ambulance attendances between 2012 and 2017. 9 Pregabalin has also been associated with an increased risk of suicide.…”

Pregabalin for neuropathic pain in primary care settings: recommendations for dosing and titration

“…Physicians need to understand and respond to their patients' concerns, and also recognize potential indicators of abuse in their patients. Recreational abuse of pregabalin and gabapentin is increasingly reported [41,42], and is a concern internationally [43][44][45][46][47] both in the scientific literature and in the lay press. While physicians need to be alert to the potential for drug misuse or misappropriation, current evidence suggests that, in patients without a current or past history of substance abuse, the risk of developing dependence on pregabalin is low [33,48].…”

“…Furthermore, subjects who reported abuse or misuse of pregabalin also frequently reported abuse of one or more other drugs [51,52]. It should be noted that overdose with pregabalin alone does not usually result in severe toxicity [32] but rather sedation and, uncommonly, seizures, unless an overdose is taken in combination with opioids or other sedatives, such as benzodiazepines [41,48,53,54]. Health-care prescribers should be aware of these data to aid treatment decisions, particularly in susceptible patients.…”