Gabapentinoid Abuse:
An Alarming Trend
Kirk Evoy, PharmD
PGY2 Ambulatory Care Resident
St. Joseph Regional Medical Center
The speaker has no actual or potential
conflicts of interest to disclose
The Current Issue
Gabapentin(GBP) and pregabalin(PRG) abuse on the rise
• PRG scripts ↑350% and GBP ↑150% in UK from 2007-2012
• 2010 list of new recreational psychoactive substances
• Warning added to European PRG labeling
• Growing black market
• Increased reports of related fatalities
Papazisis G, et al. Int J Clin Pharmacol Ther 2014. [Epub ahead of print]
Schifano F. CNS Drugs 2014.;28:491-496
Spence D. BMJ 2013;347:f6747.
Abuse Potential
• Zacny et al.
– 75 or 150 mg PRG +/- oxycodone in 16 non-drugabusing volunteers
– No abuse liability with or without oxycodone
• Pfizer study
– 450 mg PRG dose in 15 recreational drug users
– “Good drug effect”, “liking”, “high”
Zacny et al. Pharacol Biochem Behav 2012;100:560-565.
Papazisis G, et al. Int J Clin Pharmacol Ther 2014. [Epub ahead of print]
≈
30 mg diazepam
Perceived Effects of High Doses
Both sedative and dissociative/psychedelic properties
• High/stoned
• Euphoria
• Improved sociability
• Marijuana or benzodiazepine (BZD) like relaxation
• Amphetamine like trip
• Sedation
• Amnesia
• “Zombie-like” effects
Papazisis G, et al. Int J Clin Pharmacol Ther 2014. [Epub ahead of print].
Schifano F. CNS Drugs 2014.;28:491-496.
Spence D. BMJ 2013;347:f6747.
Pattern of Abuse
• Kapil et al.
– Frequency of misuse of GBP, PRG, baclofen
• Weekly: 13%
• Between weekly and monthly: 50%
• Monthly: 37%
• Schifano et al.
–
–
–
–
–
Study of web reports from 108 websites
Doses >>> recommended max
Tolerance develops and wears off rapidly
Multiple routes of administration
PRG superior to GBP
Papazisis G, et al. Int J Clin Pharmacol Ther 2014. [Epub ahead of print].
Schifano F, et al. Psychotherapy and Psychosomatics 2011.;80:118-122.
Schifano F. CNS Drugs 2014;28:491-496.
Gahr M et al. Eur J Clin Pharmacol 2013;69:1335-1342.
Dependence and Withdrawal
• Cravings, self-titration, drug-seeking suggest
dependence
• BZD or alcohol-like withdrawals
– Alleviated rapidly with resumption of gabapentenoid
– Not relieved with BZDs
• Multiple reports of relapse shortly after detox
Filipetto F, et al. JAOA 2010;110:605-607.
[Author not listed]. J Clin Psychiatry 2007;68;3:483-484.
Hellwig TR, et al. Am J Health-Syst Pharm 2010;67:910-912.
See S, et al. Ann Pharmacother 2011;45:e31.
Victorri-Vigneau C, et al. Pharmacopsychiatry 2007;40:43-44
Kruszewksi SP, et al. Journal of Psychiatric Practice 2009;15:314-319.
Gahr M, et al. J Addict Med 2013;7:147-149.
Overdose
• Reported doses up to 7.2g PRG and 90g GBP
• Rarely sole cause of death
– Completed suicide with 45g GBP
– Survived suicide attempt with 90g GBP
• Contributor in polysubstance abuse fatalities
– Additive CNS depressant effects
• Poisoning usually delayed response
Baird C, et al. Eur Addict Res 2014;20:115-118
Hakkinen M, et al. Forensic Science International 2014;241:1-6.
Middleton O. J Forensic Sci 2011;56:1373-1375.
Schauer SG, et al. Military Medicine2013;178:119. [Abstract].
Typical Abuser
•
•
•
•
•
Young males
Low income
H/O recreational drug abuse
Concomitant opiate use
Consume very high gabapentenoid doses
Boden R, et al. Eur J Clin Pharmacol 2014:70;197-204.
Schifano F. CNS Drugs 2014;28:491-496
Gahr M et al. Eur J Clin Pharmacol 2013;69:1335-1342.
Extent of the Problem
• Swedish and German national registries point toward significant
increase in abuse since 2008
• Growing trend, but number of patients still small
• UK ED visit rates (per 100,000 population)
GBP
Alcohol
2004
2.7
230.5
2011
4.9
232.5
Opioids
BZDs
67.7
58.2
178.6
136.6
Papazisis G, et al. Int J Clin Pharmacol Ther 2014. [Epub ahead of print]
Schifano F. CNS Drugs 2014;28:491-496
Hakkinen M, et al. Forensic Science International 2014;241:1-6.
Schwan S, et al. Eur J Clin Pharmacol 2010;66:947-953
Howland RH. Journal of Psychosocial Nursing 2014;52:12-15.
Next Time You Verify a Gabapentinoid,
Consider…
• Drug-seeking behaviors
• History of/risk factors for abuse
• Judicious dose escalation and prescription quantities
• Avoid abrupt discontinuation
• Appropriateness of off-label uses, especially in treating addiction
• Urine drug screens
• Alert physicians of abuse potential
• Continued post-marketing surveillance is crucial
Papazisis G, et al. Int J Clin Pharmacol Ther 2014. [Epub ahead of print]
Smith BH. British Jounral of General Practice 2012: DOI:10.3399/bjgp12X653516.
[Author not listed]. Rev Prescrire2012;32:116-118.
Questions?