BMJ 2013;347:f6747 doi: 10.1136/bmj.f6747 (Published 8 November 2013)
Page 1 of 2
Views & Reviews
VIEWS & REVIEWS FROM THE FRONTLINE
Bad medicine: gabapentin and pregabalin Des Spence general practitioner, Glasgow business too, with combined sales worth £200m (€240m; $322m) a year.7 But a word of caution: pain and anxiety symptoms are subjective, with wide variation in reported prevalence.2 The longest neuropathic pain study lasted a mere 13 weeks,6 and highly psychoactive drugs are difficult to compare with placebo.
People have died from the drugs I have prescribed. I rationalised that these drugs were prescribed in good faith, in line with guidelines, and deaths were the result of misuse. But this offers no comfort to my sense of guilt. Prescription drug misuse is a problem, especially psychoactive drugs such as opioids and benzodiazepine. And there is an iatrogenic epidemic of harm in the US with nearly 15 000 deaths annually from prescribed painkillers. This is the tiny tip of an abuse iceberg, with an estimated 12 million Americans misusing these drugs recreationally.1 We have a social and professional responsibility to be cautious in how we prescribe psychoactive drugs. Increasingly, I confront drug seeking behaviours for different drugs—gabapentin and pregabalin. Could it be that these seemingly harmless epilepsy drugs are being misused? Gabapentin and pregabalin are in fact also licensed for neuropathic pain, and pregabalin for general anxiety disorder. These are common and chronic conditions, together affecting 20% to 40% of the population.2 3 Their prescribing is anointed by Cochrane reviews4 5 and a NICE guideline6: gold plated evidence of benefit. Gabapentin and pregabalin are being prescribed freely and rapid dose up titration is recommended. Pregabalin prescribing has increased by 350% in just five years, to 2.7 million scripts. Likewise gabapentin prescribing has increased 150% in five years, with 3.5 million scripts.7 This stellar prescribing growth seems set to continue. And this is big
And there is increasing published evidence of concern about the abuse of pregabalin and gabapentin,8 9 10 and these drugs are now commonly being detected in toxicology in autopsies after drug overdoses.11 So what is the motivation to misuse these drugs? Users describe the effects as the “ideal psychotropic drug,” “great euphoria,” “disassociation,” and “opiate buzz,” and are achieving these effects by taking large quantities as a single dose.10 Accordingly there is a growing black market, and these drugs are being bought through online pharmacies. The US recognises the problems associated with pregabalin, which has now become a scheduled drug under the Controlled Substance Act.12 Is the UK ignoring the misuse of pregabalin and gabapentin? Should we re-examine the so called evidence for gabapentin and pregabalin and consider alternatives?13 14 For the risk from iatrogenic harm is bad medicine indeed. Time to tackle the rise and rise of gabapentin and pregabalin prescribing? Competing interests: I have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; not externally peer reviewed. 1 2 3 4 5 6
7 8
Centers for Disease Control and Prevention. Policy impact: prescription painkiller overdoses. July 2013. www.cdc.gov/homeandrecreationalsafety/rxbrief/. Gureje O, Von Korff M, Simon GE, Gater R. Persistent pain and well-being: a World Health Organization study in primary care. JAMA 1998;280:147-51. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:617-27. Moore RA, Wiffen PJ, Derry S, McQuay HJ Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2011;3:CD007938. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev 2009;3:CD007076. National Institute for Health and Clinical Excellence (NICE). Neuropathic pain: the pharmacological management of neuropathic pain in adults in non-specialist settings. NICE clinical guideline 96. March 2010. www.nice.org.uk/nicemedia/live/12948/47936/ 47936.pdf. Health and Social Care Information Centre. Prescription Cost Analysis—England, 2012. 4 April 2013. https://catalogue.ic.nhs.uk/publications/prescribing/primary/pres-cost-analeng-2012/pres-cost-anal-eng-2012a-rep.pdf. Smith BH, Higgins C, Baldacchino A, Kidd B, Bannister J. Substance misuse of gabapentin. Br J Gen Pract 2012;62:406-7.
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BMJ 2013;347:f6747 doi: 10.1136/bmj.f6747 (Published 8 November 2013)
Page 2 of 2
VIEWS & REVIEWS
9 10
11 12
Millar J, Sadasivan S, Weatherup N, Lutton S. Lyrica nights–recreational pregabalin abuse in an urban emergency department. Emerg Med J 2013;30:874. Schifano F, D’Offizi S, Piccione M, Corazza O, Deluca P, Davey Z, et al. Is there a recreational misuse potential for pregabalin? Analysis of anecdotal online reports in comparison with related gabapentin and clonazepam data. Psychother Psychosom 2011;80:118-22. Maskell PD. Gabapentin and pregabalin abuse by heroin users. [electronic response to Stannard C. Opioids in the UK: what’s the problem?] BMJ 2013. www.bmj.com/content/ 347/bmj.f5108/rr/665800. US Drug Enforcement Agency (DEA). Drug scheduling. www.justice.gov/dea/druginfo/ds. shtml.
For personal use only: See rights and reprints http://www.bmj.com/permissions
13 14
Wiffen PJ, Derry S, Moore RA, Aldington D, Cole P, Rice ASC, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia (Protocol). Cochrane Database Syst Rev 2013;6:CD010567. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain and fibromyalgia in adults (Review). Cochrane Database Syst Rev 2012;12:CD008242.
Cite this as: BMJ 2013;347:f6747 © BMJ Publishing Group Ltd 2013
Subscribe: http://www.bmj.com/subscribe
Page 1 of 2
Views & Reviews
VIEWS & REVIEWS FROM THE FRONTLINE
Bad medicine: gabapentin and pregabalin Des Spence general practitioner, Glasgow business too, with combined sales worth £200m (€240m; $322m) a year.7 But a word of caution: pain and anxiety symptoms are subjective, with wide variation in reported prevalence.2 The longest neuropathic pain study lasted a mere 13 weeks,6 and highly psychoactive drugs are difficult to compare with placebo.
People have died from the drugs I have prescribed. I rationalised that these drugs were prescribed in good faith, in line with guidelines, and deaths were the result of misuse. But this offers no comfort to my sense of guilt. Prescription drug misuse is a problem, especially psychoactive drugs such as opioids and benzodiazepine. And there is an iatrogenic epidemic of harm in the US with nearly 15 000 deaths annually from prescribed painkillers. This is the tiny tip of an abuse iceberg, with an estimated 12 million Americans misusing these drugs recreationally.1 We have a social and professional responsibility to be cautious in how we prescribe psychoactive drugs. Increasingly, I confront drug seeking behaviours for different drugs—gabapentin and pregabalin. Could it be that these seemingly harmless epilepsy drugs are being misused? Gabapentin and pregabalin are in fact also licensed for neuropathic pain, and pregabalin for general anxiety disorder. These are common and chronic conditions, together affecting 20% to 40% of the population.2 3 Their prescribing is anointed by Cochrane reviews4 5 and a NICE guideline6: gold plated evidence of benefit. Gabapentin and pregabalin are being prescribed freely and rapid dose up titration is recommended. Pregabalin prescribing has increased by 350% in just five years, to 2.7 million scripts. Likewise gabapentin prescribing has increased 150% in five years, with 3.5 million scripts.7 This stellar prescribing growth seems set to continue. And this is big
And there is increasing published evidence of concern about the abuse of pregabalin and gabapentin,8 9 10 and these drugs are now commonly being detected in toxicology in autopsies after drug overdoses.11 So what is the motivation to misuse these drugs? Users describe the effects as the “ideal psychotropic drug,” “great euphoria,” “disassociation,” and “opiate buzz,” and are achieving these effects by taking large quantities as a single dose.10 Accordingly there is a growing black market, and these drugs are being bought through online pharmacies. The US recognises the problems associated with pregabalin, which has now become a scheduled drug under the Controlled Substance Act.12 Is the UK ignoring the misuse of pregabalin and gabapentin? Should we re-examine the so called evidence for gabapentin and pregabalin and consider alternatives?13 14 For the risk from iatrogenic harm is bad medicine indeed. Time to tackle the rise and rise of gabapentin and pregabalin prescribing? Competing interests: I have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; not externally peer reviewed. 1 2 3 4 5 6
7 8
Centers for Disease Control and Prevention. Policy impact: prescription painkiller overdoses. July 2013. www.cdc.gov/homeandrecreationalsafety/rxbrief/. Gureje O, Von Korff M, Simon GE, Gater R. Persistent pain and well-being: a World Health Organization study in primary care. JAMA 1998;280:147-51. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:617-27. Moore RA, Wiffen PJ, Derry S, McQuay HJ Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2011;3:CD007938. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev 2009;3:CD007076. National Institute for Health and Clinical Excellence (NICE). Neuropathic pain: the pharmacological management of neuropathic pain in adults in non-specialist settings. NICE clinical guideline 96. March 2010. www.nice.org.uk/nicemedia/live/12948/47936/ 47936.pdf. Health and Social Care Information Centre. Prescription Cost Analysis—England, 2012. 4 April 2013. https://catalogue.ic.nhs.uk/publications/prescribing/primary/pres-cost-analeng-2012/pres-cost-anal-eng-2012a-rep.pdf. Smith BH, Higgins C, Baldacchino A, Kidd B, Bannister J. Substance misuse of gabapentin. Br J Gen Pract 2012;62:406-7.
[email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2013;347:f6747 doi: 10.1136/bmj.f6747 (Published 8 November 2013)
Page 2 of 2
VIEWS & REVIEWS
9 10
11 12
Millar J, Sadasivan S, Weatherup N, Lutton S. Lyrica nights–recreational pregabalin abuse in an urban emergency department. Emerg Med J 2013;30:874. Schifano F, D’Offizi S, Piccione M, Corazza O, Deluca P, Davey Z, et al. Is there a recreational misuse potential for pregabalin? Analysis of anecdotal online reports in comparison with related gabapentin and clonazepam data. Psychother Psychosom 2011;80:118-22. Maskell PD. Gabapentin and pregabalin abuse by heroin users. [electronic response to Stannard C. Opioids in the UK: what’s the problem?] BMJ 2013. www.bmj.com/content/ 347/bmj.f5108/rr/665800. US Drug Enforcement Agency (DEA). Drug scheduling. www.justice.gov/dea/druginfo/ds. shtml.
For personal use only: See rights and reprints http://www.bmj.com/permissions
13 14
Wiffen PJ, Derry S, Moore RA, Aldington D, Cole P, Rice ASC, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia (Protocol). Cochrane Database Syst Rev 2013;6:CD010567. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain and fibromyalgia in adults (Review). Cochrane Database Syst Rev 2012;12:CD008242.
Cite this as: BMJ 2013;347:f6747 © BMJ Publishing Group Ltd 2013
Subscribe: http://www.bmj.com/subscribe
