Pregabalin Misuse and Abuse: A Scoping Review of Extant Literature

• Author: Mayyada Wazaify,Amneh Al-Husseini,Marie Claire Van Hout
• Published date: 01 July 2018
• Date: 01 July 2018
• DOI: http://doi.org/10.1177/0022042618759487
• Subject Matter: Articles

https://doi.org/10.1177/0022042618759487

Journal of Drug Issues

2018, Vol. 48(3) 356 –376

© The Author(s) 2018

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DOI: 10.1177/0022042618759487

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Article

Pregabalin Misuse and Abuse:

A Scoping Review of Extant

Literature

Amneh Al-Husseini1, Marie Claire Van Hout2,

and Mayyada Wazaify1

Abstract

Prescribing of pregabalin is increasing worldwide with public health concerns centering on

misuse and abuse of prescribed and diverted pregabalin. To describe and map what is known

about misuse and abuse of pregabalin, a scoping review of available published literature was

undertaken. A scoping review methodology was used to identify and map available literature on

misuse and abuse of prescribed and diverted pregabalin. Four themes emerged on the misuse

and abuse of pregabalin: (a) abuse potential, (b) prevalence of abuse, (c) risk and predisposition,

and (d) consequences of abuse. Fifty-four records were reviewed and charted. Of note was

the dearth of research on the topic prior to 2005, with increased interest in pregabalin abuse

potential from 2010 onward. Available literature supports concern around abuse potential of

pregabalin, especially among patients with a history of substance abuse. Prescribers should

adopt more rational prescribing.

Keywords

pregabalin, abuse, misuse, dependence, prescription drug

Introduction

By definition, any medication can be misused, but few have abuse potential, and particularly

those with mind-altering or body-shaping properties (Hughes, McElnay, Hughes, & McKenna,

1999). The most commonly abused prescription medications worldwide are stimulants (methyl-

phenidate) used for treating attention deficit hyperactivity disorder (ADHD), central nervous

system (CNS) depressants such as sedatives (benzodiazepines; National Institute on Drug Abuse

[NIDA], 2014), and anticonvulsants (pregabalin; Loftus & Wright, 2014). The risk of depen-

dence on such prescription drugs increases when they are used in ways other than prescribed, for

example, at higher doses, by different routes of administration, or with a combination of alcohol

or other drugs (NIDA, 2014). Adverse health and social consequences of prescription medicine

abuse and dependence are steadily worsening worldwide, and are reflected in increased treatment

1University of Jordan, Amman, Jordan

2Liverpool John Moores University, UK

Corresponding Author:

Marie Claire Van Hout, Professor of Public Health Policy and Practice, Public Health Institute, Liverpool John Moores

University, Webster Street Liverpool L32ET, UK.

Email: m.c.vanhout@ljmu.ac.uk

759487JODXXX10.1177/0022042618759487Journal of Drug IssuesAl-Husseini et al.

research-article2018

Al-Husseini et al. 357

admissions, emergency room visits, and overdose deaths from drugs such as opioids, CNS

depressants, and stimulants (NIDA, 2014). This is particularly evident in the United States, cur-

rently experiencing an opioid crisis. In Europe, the European Monitoring Centre for Drugs and

Drug Addiction (EMCDDA) and European Medicines Agency (EMA) currently exchange warn-

ing trend information around abuse of medicinal products, and with key examples including

carfentanil, pregabalin, etaqualone, zopiclone, phenibut, gabapentin, and tropicamide (EMCDDA,

2014; EMCDDA & Europol, 2013).

Of interest for this scoping review is the drug known as pregabalin which is an analogue of the

gamma-aminobutyric acid (GABA) neurotransmitter, and approved for the treatment of partial

epilepsy, generalized anxiety disorder (GAD), peripheral and central neuropathic pain, and fibro-

myalgia (Papazisis & Tzachanis, 2014). Pregabalin decreases central neuronal excitability by

binding to an auxiliary subunit (α2-δ protein) of a voltage-gated calcium channel on neurons in

the CNS and reduces the release of several neurotransmitters, including glutamate, noradrena-

line, and substance P (Schwan, Sundström, Stjernberg, Hallberg, & Hallberg, 2010). The poten-

tial for abuse and/or physical dependence on pregabalin was originally assessed to be low at the

time of marketing authorization (Schwan et al., 2010). However, it was noted that euphoria

occurred as an adverse event in clinical trials among 1% to 10% of patients depending on dose,

compared with 0.5% for placebo (Schwan et al., 2010). Of particular concern is that global pre-

scribing of pregabalin is increasing, with total sales projected to reach US$3.3 billion by 2018

(Mackey, 2010). Pregabalin is controlled in Jordan, Norway, and in the United States by the

Jordan Food and Drug Administration, the EMA, and the American Drug Enforcement

Administration, respectively (Blommel & Blommel, 2007; Bramness, Sandvik, Engeland, &

Skurtveit, 2010; Jordan Food and Drug Administration, 2017). Diverted and off-label use of

pregabalin is also on the increase in Europe (EMCDDA, 2014; EMCDDA & Europol, 2013) and

in the Middle East (Al-Husseini, Wazaify, & Van Hout, 2017). Profiles of pregabalin abuse gen-

erally involve individuals with a history of abuse of other medications (Häkkinen, Vuori, Kalso,

Gergov, & Ojanperä, 2014; Papazisis & Tzachanis, 2014). To describe and collate what is known

about misuse and abuse of pregabalin, a scoping review of available published data on misuse

and abuse of prescribed and diverted pregabalin was undertaken.

Method

Scoping review methods are increasingly popular as an accepted review approach (Arskey &

O’Malley, 2005; Hidalgo Landa, Szabo, Le Brun, Owen, & Fletcher, 2011) and are used to “map

the literature on a particular topic or research area and provide an opportunity to identify key

concepts; gaps in the research; and types and sources of evidence to inform practice, policymak-

ing, and research” (p.1-20) (Daudt, van Mossel, & Scott, 2013). This form of descriptive synthe-

sis is generally used to provide descriptive summaries of the literature, across a broad range of

methodologies and study designs, summarize and publish findings of the research, and identify

gaps in the current literature (Arskey & O’Malley, 2005; Brien, Lorenzetti, Lewis, Kennedy, &

Ghali, 2010; Rumrill, Fitzgerald, & Merchant, 2010). The scoping review was underpinned by

the research question, “What do we know about the misuse and abuse of pregabalin?” The

research team adopted the five-stage method as developed by Arskey and O’Malley (2005) that

included (a) identifying the essential research question, (b) searching for similar studies, (c)

study selection, (d) charting the data, and (e) collecting, summarizing, and recording the results.

A thorough and systematic search of literature (1990-2017) was conducted by the team using

the following university databases: ScienceDirect, Electronic Library of Medicine, Hinari,

Google Scholar, Cochrane Library, and PubMed. A comprehensive list of search terms was cre-

ated by the team, which consisted of two pharmacists and an addiction/public health specialist.

Searches combined the terms pregabalin with abuse, misuse, dependence, and prescription drug.