Use of Pregabalin – A Nationwide Pharmacoepidemiological Drug Utilization Study with Focus on Abuse Potential

Abstract

Introduction: Pregabalin is currently approved for the treatment of epilepsy, generalized anxiety disorder and neuropathic pain with a licensed dosage range of 150 mg to 600 mg/day. Growing concern about the abuse potential of pregabalin is partly based on reports of pregabalin being used in dosages that exceed the approved therapeutic range.

Methods: To identify predictors of pregabalin use above recommended dosage, we conducted a pharmacoepidemological drug utilization study using the Danish nationwide registers. We deployed 4 measures of abuse: high use (≥600 mg/day) or very high use (≥1 200 mg/day) over a 6- or 12-month period, respectively. Multiple logistic regression was used to identify patient and treatment characteristics that were associated with either abuse marker.

Results: Out of 42 520 pregabalin users 4 090 (9.6%) were treated with more than 600 mg/day for 6 months and 2 765 (6.5%) for more than 12 months. Male gender and prescription of antipsychotics and benzodiazepines were associated with increased risk of use of above the recommended dosage.

Discussion: Use of pregabalin above recommended dosages was rare but abuse may occur in susceptible patients.

Key words

pregabalin - abuse - drug utilization - denmark

• References

• 1 Halaby A, Kassam SA, Naja WJ. Pregabalin dependence: a case report. Curr Drug Saf 2014;
• 2 Cho YW, Song ML. Effects of pregabalin in patients with hypnotic-dependent insomnia. J Clin Sleep Med 2014; 10: 545-550
• 3 Oulis P, Kalogerakou S, Anyfandi E et al. Cognitive effects of pregabalin in the treatment of long-term benzodiazepine-use and dependence. Hum Psychopharmacol 2014; 29: 224-229
• 4 Guglielmo R, Martinotti G, Clerici M et al. Pregabalin for alcohol dependence: a critical review of the literature. Adv Ther 2012; 29: 947-957
• 5 Gahr M, Franke B, Freudenmann RW et al. Concerns about pregabalin: further experience with its potential of causing addictive behaviors. J Addict Med 2013; 7: 147-149
• 6 Chalabianloo F, Schjott J. Pregabalin and its potential for abuse. Tidsskr Nor Laegeforen 2009; 129: 186-187
• 7 Schjerning O, Rosenzweig M, Pottegard A et al. Abuse potential of pregabalin: a systematic review. CNS Drugs. 2016
• 8 Zaccara G, Gangemi P, Perucca P et al. The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials. Epilepsia 2011; 52: 826-836
• 9 Papazisis G, Garyfallos G, Sardeli C et al. Pregabalin abuse after past substance-seeking behavior. Int J Clin Pharmacol Ther 2013; 51: 441-442
• 10 Halaby A, Kassm SA, Naja WJ. Pregabalin dependence: a case report. Curr Drug Saf 2015; 10: 184-186
• 11 Jonsson B, Backman E, Salmonson H et al. Injection of crushed tablets – a prospective observational study. Clin Toxicol (Phila) 2014; 52: 982-983
• 12 Carrus D, Schifano F. Pregabalin misuse-related issues; intake of large dosages, drug-smoking allegations, and possible association with myositis: two case reports. J Clin Psychopharmacol 2012; 32: 839-840
• 13 Grosshans M, Lemenager T, Vollmert C et al. Pregabalin abuse among opiate addicted patients. Eur J Clin Pharmacol 2013; 69: 2021-2025
• 14 Boden R, Wettermark B, Brandt L et al. Factors associated with pregabalin dispensing at higher than the approved maximum dose. Eur J Clin Pharmacol 2014; 70: 197-204
• 15 Nose M, Tansella M, Thornicroft G et al. Is the Defined Daily Dose system a reliable tool for standardizing antipsychotic dosages?. International clinical psychopharmacology 2008; 23: 287-290
• 16 Hallas J, Nissen A. Individualized drug utilization statistics. Analysing a population’s drug use from the perspective of individual users. Eur J Clin Pharmacol 1994; 47: 367-372
• 17 Hallas J, Stovring H. Templates for analysis of individual-level prescription data. Basic Clin Pharmacol Toxicol 2006; 98: 260-265
• 18 Birt J, Johnston J, Nelson D. Exploration of claims-based utilization measures for detecting potential nonmedical use of prescription drugs. J Manag Care Spec Pharm 2014; 20: 639-646
• 19 Nielsen J, Roge R, Schjerning O et al. Geographical and temporal variations in clozapine prescription for schizophrenia. Eur Neuropsychopharmacol 2012; 22: 818-824
• 20 Wallach-Kildemoes H, Skovgaard AM, Thielen K et al. Social adversity and regional differences in prescribing of ADHD medication for school-age children. J Dev Behav Pediatr 2015; 36: 330-341
• 21 Pottegard A, Bjerregaard BK, Glintborg D et al. The use of medication against attention deficit hyperactivity disorder in Denmark: a drug use study from a national perspective. Eur J Clin Pharmacol 2012; 68: 1443-1450
• 22 Henriksen DP, Rasmussen L, Hansen MR et al. Comparison of the five Danish regions regarding demographic characteristics, healthcare utilization, and medication use – a descriptive cross-sectional study. PLoS One 2015; 10: e0140197
• 23 Freedman BM, O’Hara E. Pregabalin has opioid-sparing effects following augmentation mammaplasty. Aesthet Surg J 2008; 28: 421-424
• 24 Kammerer N, Lemenager T, Grosshans M et al. Pregabalin for the reduction of opiate withdrawal symptoms. Psychiatr Prax 2012; 39: 351-352
• 25 Hadley SJ, Mandel FS, Schweizer E. Switching from long-term benzodiazepine therapy to pregabalin in patients with generalized anxiety disorder: a double-blind, placebo-controlled trial. J Psychopharmacol 2012; 26: 461-470
• 26 Oulis P, Masdrakis VG, Karakatsanis NA et al. Pregabalin in the discontinuation of long-term benzodiazepine use: a case-series. Int Clin Psychopharmacol 2008; 23: 110-112
• 27 Ben-Menachem E. Weight issues for people with epilepsy – a review. Epilepsia 2007; 48 (Suppl. 09) 42-45
• 28 Yargic I, Ozdemiroglu FA. Pregabalin abuse: a case report/Pregabalin kötüye kullanımı: Bir olgu sunumu. Klinik Psikofarmakoloji Bülteni/Bulletin of Clinical Psychopharmacology 2011; 64-66
• 29 Skopp G, Zimmer G. Pregabalin – a drug with abuse potential?. Arch Kriminol 2012; 229: 44-54
• 30 Grosshans M, Mutschler J, Hermann D et al. Pregabalin abuse, dependence, and withdrawal: a case report. Am J Psychiatry 2010; 167: 869
• 31 Rutten K, De Vry J, Robens A et al. Dissociation of rewarding, anti-aversive and anti-nociceptive effects of different classes of anti-nociceptives in the rat. Eur J Pain 2011; 15: 299-305
• 32 Andrews N, Loomis S, Blake R et al. Effect of gabapentin-like compounds on development and maintenance of morphine-induced conditioned place preference. Psychopharmacology (Berl) 2001; 157: 381-387
• 33 Filipetto FA, Zipp CP, Coren JS. Potential for pregabalin abuse or diversion after past drug-seeking behavior. J Am Osteopath Assoc 2010; 110: 605-607
• 34 Kapil V, Green JL, Le Lait M-C et al. Misuse of the γ-aminobutyric acid analogues baclofen, gabapentin and pregabalin in the UK. British Journal of Clinical Pharmacology 2014; 78: 190-191