1. INTRODUCTION
Gabapentinoids are top selling drugs globally. In 2018, gabapentin became the 6th most commonly prescribed medication in the US, increasing from 39 million scripts in 2012 to 67 million scripts in 2018.(1, 2) In Australia, pregabalin prescribing increased eight fold between 2012 and 2018. (3) However, the global increase in gabapentinoid prescribing has been associated with subsequent increases in the harms including misuse of these drugs. Recently, gabapentinoids have been increasingly prescribed by physicians for several “off-label” uses, such as low back pain and sciatica. (4, 5) Whilst this escalation in off-label prescribing may, in part, have been in response to the challenges of the opioid epidemic and the subsequent push towards using non-opioid alternatives for pain management, (2, 4, 6) recent studies have found limited evidence supporting these off-label uses and demonstrated gabapentinoids to be no more efficacious than placebo. (4, 5, 7, 8)
The emerging issue of gabapentinoid misuse is recognised across several countries, including North America and in Europe. (9-11) In Australia, one in seven Australians prescribed pregabalin are considered at being at high risk of misuse. (12) Since its listing on the subsidised list of medicines in Australia (Pharmaceutical Benefits Scheme) in 2013, pregabalin-associated deaths have increased by 57.8% per year, highlighting the rapidly increasing harms associated with the increased prescribing trends. (12) Some people who purposively take higher than recommended doses do so to experience sedation, euphoric effects, disassociation, analgesia and to potentiate the effects of other substances (e.g. opioids). (2) Concomitant consumption of gabapentinoids with other central nervous system depressants (e.g. benzodiazepines) and opioid analgesics significantly increases adverse events, such as respiratory depression and mortality. (2, 13) Moreover, gabapentinoid use has also been associated with increased risks of suicidal ideation and behaviour, particularly within adolescents and young adults (15-24 years) and women. (14-16) Furthermore, physical dependence, tolerance and withdrawal from gabapentinoids have been well documented at both recommended dosages and supratherapeutic dosages. (2, 14, 17, 18)
In cases where a drug is no longer needed or is associated with more harms than benefits, the medicine should cease (or reduce in dose). Deprescribing is the complex process of tapering or ceasing unnecessary medication, aimed at improving patient outcomes. (19) Deprescribing is most often indicated when the potential harms of a drug begin to outweigh the existing or potential benefits of continued treatment and is often prompted by the emergence of new adverse events, increase in the number of medicines being taken, or changing treatment priorities. (19, 20) Whilst prescribing a new medication is a relatively simple and often a well-received process, how and when to consider deprescribing can be more complicated. More so, deprescribing a medication that has a high risk of dependence, misuse and withdrawal can be an even more difficult task. Currently, there is no consensus on the best method to deprescribe gabapentinoids.
It is essential that clinicians have access to current evidence supporting the safe cessation of gabapentinoids. In order to deprescribe successfully, prescribers can be guided by strategies that have proved to be effective in the past. There is a clear lack of robust evidence in the literature surrounding tapering or ceasing gabapentinoid therapy. Previous research in deprescribing has been in other populations. For example, in older people or people living with dementia, or those prescribed a specific drug class, such as anticholinergics or opioid analgesics. (21-24) Thus, there is fundamental need and clinical value to investigate what strategies are effective to deprescribe gabapentinoids. Therefore, this review aimed to investigate the types and nature of previous gabapentinoid deprescribing interventions in adults, either in reducing gabapentinoid use (i.e. dose reduction/cessation) or the prescribing of gabapentinoids.