Pregabalin misuse: the next wave of prescription medication problems

Overseas experience need not portend the future of prescription drug misuse in Australia

Dispensing data indicate that pregabalin prescribing in Australia is rising rapidly, and the numbers of self‐poisonings and deaths are also increasing.1 This mirrors the European and North American experience of escalating misuse and harms.2,3 Although Australian guidelines recommend it only as second line treatment for neuropathic pain,4 pregabalin is now the seventh most expensive drug in terms of Pharmaceutical Benefits Scheme (PBS) expenditure.5

In this issue of the Journal, Crossin and colleagues6 describe worrying trends in pregabalin‐related harms. They identified a more than tenfold increase in the number of pregabalin‐related ambulance attendances in Victoria during 2012–2017, correlated strongly with rising prescribing rates. Half the attendances were for people defined as being at high risk of pregabalin misuse because of their history of substance misuse, self‐harm, or mental health problems. A concomitant increase in pregabalin‐related fatalities has been reported by the Victorian coroner. The authors advocate scheduling changes and interval dispensing as appropriate responses to these developments.6

The United Kingdom has similar problems, and is responding by controlling pregabalin by re‐scheduling it under Schedule 3 of the Misuse of Drug Regulations 2001. The fundamental problem that much current pregabalin prescribing is probably inappropriate has also been recognised.7

The sharp rise in the numbers of deaths attributed to prescription opioids has led to prescribers appropriately reconsidering prescribing them for people with persistent pain. Pregabalin may be prescribed more frequently for chronic non‐malignant pain in the perception that it is safer than opioid medications.7

Neuropathic pain is the only pain indication for PBS‐funded pregabalin, but diagnosing this condition is challenging. A structured approach is needed: history taking and examination followed by correlation of signs and symptoms with the putative somatosensory lesion. Dermatome and myotome charts may assist interpretation of the neuroanatomic distribution of signs. Pathology investigations may support the diagnosis, but are not always needed.4

Chronic back problems are common in Australia, with a prevalence in 2014–15 of 16%.8 A 2017 meta‐analysis found that the benefits of pregabalin for people with non‐specific chronic low back pain were minimal, and the risks significant.9 A recent Australian study of people with acute or chronic sciatica found that pregabalin did not reduce pain or improve function, even when the history and examination of the patient indicated neuropathy.10

Is poor access to multidisciplinary pain clinics and community‐based non‐pharmacological pain management strategies encouraging overuse of pregabalin? The importance of a comprehensive pain management plan, in which medications are only one component, is recognised.4 Given the limited efficacy of biomedical approaches, pain management practitioners are increasingly moving towards integrated, lifestyle‐focused strategies for patients with chronic pain.11

The cumulative number needed to treat (NNT) derived from several trials of pregabalin treatment for patients with neuropathic pain was 7.7, and the number needed to harm (NNH) 13.9.4 In real world practice, the NNT/NNH balance will be less favourable because of diagnostic uncertainty, overprescribing, and harms caused by misuse and diversion not assessed in clinical trials.

In the study by Crossin and her co‐authors, almost 50% of pregabalin‐related ambulance attendances were for people at high risk of pregabalin misuse.6 Another recent study1 found that 14% of Australians prescribed pregabalin are at high risk. Increasing misuse of pregabalin in prisons has also been reported.7 Heroin users report that the effect of heroin is enhanced and those of opioid withdrawal ameliorated by pregabalin, but they also appreciate the risk of overdose.2 People at risk of pregabalin misuse should be ensured access to good pain management, including non‐pharmacological approaches, and to treatment of opioid dependence, such as methadone or buprenorphine.

The innovative analysis by Crossin and colleagues of ambulance callout data for identifying harms complements studies based on Poisons Information Centre call frequencies, coronial databases, data linkage, and drug treatment service user interviews1,2,3 as an important pharmacovigilance strategy that allows the extent and progression of pharmaceutical drug misuse to be assessed. In contrast, they note that adverse event reporting to the Therapeutic Goods Administration is deficient in this respect.

Crossin and her co‐authors acknowledge that a limitation of their study was that the appropriateness of prescribing and the source of diverted pregabalin could not be determined. The extent to which industry marketing to consumers and health care practitioners is exacerbating this problem is also unknown. Similarly, the contribution of internet‐based medication suppliers should be examined.

Interval dispensing for people at high risk of misuse and re‐scheduling pregabalin may play roles in responding to the problem of pregabalin misuse, but the broader treatment environment must also be considered. Decisions about prescribing and de‐prescribing pregabalin should balance the benefit to the patient against the risk to both the individual and their community. We need to “rethink pain”11 and to improve the availability of multidisciplinary treatment. North America need not be the portent of a dystopian future of prescription drug misuse in Australia.