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.