Pregabalin abuse and dependence during insomnia and protocol for short-term withdrawal management with diazepam: examples from case reports

 

 Permissions and Reprints

Introduction: Pregabalin (PGN) is an anxiolytic, analgesic, antiepileptic, and hypnotic medication. There are concerns about its abuse in the community for managing chronic insomnia and other risks when assumed in overdose or combination with other abuse substances. PGN is classified as a controlled medication. While its discontinuation is accompanied by rebound insomnia and other neurological symptoms, cross-tapering PGN with short-term diazepam (DZ) during inpatient admissions has shown promising results in dealing with PGN withdrawal symptoms accompanied by rebound insomnia.

Material and Methods: We report three cases that began abusing their prescribed PGN. During hospital admission, our teams used a protocol for cross-tapering PGN with DZ to reduce withdrawal symptoms. Other sedative medications are suspended while alcohol is not allowed if patients are on leave from the hospital. Standardized scales for assessment were clinical global impression scale-severity (CGI-S), generalized anxiety disorder scale (GAD-7), and insomnia severity index (ISI).

Results: The cross-tapering PGN with DZ showed similar clinical outcomes with reduced withdrawal symptoms and rebound insomnia during two weeks of cross-tapering. Eventually, DZ, too, is stopped in the hospital to avoid another dependence syndrome.

Conclusion: As emerging in the current study, PGN has strong addictive effects in people who have insomnia and is mostly abused for its hypnotic or sleep-inducing properties when other medications have failed. As applied in the current study, DZ can manage PGN withdrawal symptoms with rebound insomnia while cross-tapering. DZ is then discontinued.

Publication History

Received: 25 November 2020

Accepted: 19 March 2021

Article published online:
30 November 2023

© 2023. Brazilian Sleep Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

• REFERENCES

• 1 American Academy of Sleep Medicine (AASM). International classification of sleep disorders. 3rd ed. Darien, IL: AASM; 2014.
• 2 Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev. 2002 Apr;6(2):97-111.
• 3 Everitt H, Baldwin DS, Stuart B, Lipinska G, Mayers A, Malizia AL, et al. Antidepressants for insomnia in adults. Cochrane Database Syst Rev. 2018 May;5(5):CD010753.
• 4 Di Iorio G, Matarazzo I, Di Tizio L, Martinotti G. Treatment-resistant insomnia treated with Pregabalin. Eur Rev Med Pharmacol Sci. 2013 Jun;17(11):1552-4.
• 5 Houghton KT, Forrest A, Awad A, Atkinson LZ, Stockton S, Harrison PJ, et al. Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis. BMJ Open. 2017 Mar;27(3):e013433.
• 6 Holsboer-Trachsler E, Prieto R. Effects of pregabalin on sleep in generalized anxiety disorder. Int J Neuropsychopharmacol. 2013 May;16(4):925-36.
• 7 Haas S, Otte A, Weerd A, Van Erp G, Cohen A, Van Gerven J. Exploratory polysomnographic evaluation of pregabalin on sleep disturbance in patients with epilepsy. J Clin Sleep Med. 2007 Aug;3(5):473-8.
• 8 Cho YW, Song ML. Effects of pregabalin in patients with hypnoticdependent insomnia. J Clin Sleep Med. 2014 May;10(5):545-50.
• 9 Kämmerer N, Lemenager T, Grosshans M, Kiefer F, Hermann D. Pregabalin for the reduction of opiate withdrawal symptoms. Psychiatr Prax. 2012 Oct;39(7):351-2.
• 10 Förg A, Hein J, Volkmar K, Winter M, Richter C, Heinz A, et al. Efficacy and safety of pregabalin in the treatment of alcohol withdrawal syndrome: a randomized placebo-controlled trial. Alcohol Alcohol. 2012 Mar/Apr;47(2):149-55.
• 11 Russell IJ, Crofford LJ, Leon T, Cappelleri JC, Bushmakin AG, Whalen E, et al. The effects of pregabalin on sleep disturbance symptoms among individuals with fibromyalgia syndrome. Sleep Med. 2009 Jun;10(6):604-10.
• 12 Sabatowski R, Gálvez R, Cherry DA, Jacquot F, Vincent E, Maisonobe P, et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial. Pain. 2004 May;109(1-2):26-35.
• 13 Roth T, Arnold LM, Garcia-Borreguero D, Resnick M, Clair AG. A review of the effects of pregabalin on sleep disturbance across multiple clinical conditions. Sleep Med Rev. 2014 Jun;18(3):261-71.
• 14 Houghton KT, Forrest A, Awad A, Atkinson L, Stockton S, Harrison PJ, et al. Biological rationale and potential clinical use of gabapentin and Pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis. BMJ Open. 2017 Mar;7(3):e013433.
• 15 Bazil CW, Dave J, Cole J, Stalvey J, Drake E. Pregabalin increases slowwave sleep and may improve attention in patients with partial epilepsy and insomnia. Epilepsy Behav. 2012 Apr;23(4):422-5.
• 16 Grosshans M, Mutschler J, Hermann D, Klein O, Dressing H, Kiefer F, et al. Pregabalin abuse, dependence, and withdrawal: a case report. Am J Psychiatry. 2010 Jul;167(7):869.
• 17 Evoy KE, Morrison MD, Saklad SR. Abuse and misuse of pregabalin and gabapentin. Drugs. 2017 Mar;77(4):403-26.
• 18 Papanna B, Lazzari C, Kulkarni K, Perumal S. Pregabalin abuse as a sleep medication: case reports. Sleep Med Dis Int J. 2020;4(2):40-2.
• 19 Morin CM, Bélanger L, Bernier F. Correlates of benzodiazepine use in individuals with insomnia. Sleep Med. 2004 Sep;5(5):457-62.
• 20 Naveed S, Faquih AE, Chaudhary A. Pregabalin-associated discontinuation symptoms: a case report. Cureus. 2018 Oct;10(10):e3425.
• 21 U. S. National Library of Medicine (NIH). Pregabalin [Internet]. Bethesda, MD: Medline Plus; 2020; [access in 2020 Nov 21]. Available from: https://medlineplus.gov/druginfo/meds/a605045. html#:~:text=If%20you%20suddenly%20stop%20taking%20 pregabalin%2C%20you%20may,your%20dose%20gradually%20 over%20at%20least%201%20week
• 22 Iacobucci G. UK government to reclassify pregabalin and gabapentin after rise in deaths. BMJ. 2017 Sep;358:j4441.
• 23 Stannard C. Misuse of gabapentin and pregabalin: a marker for a more serious malaise?. Addiction. 2016 Oct;111(10):1699-700.
• 24 Lazzari C, Nusair A. Pregabalin addiction and withdrawal in primary and secondary care. Eur Psychiatry. 2019 Apr;56(Suppl 1):S208.
• 25 Gahr M, Freudenmann RW, Kölle MA, Schönfeldt-Lecuona C. Pregabalin and addiction: lessons from published cases. J Subst Use. 2014 Oct;19(6):448-9.
• 26 Van Hout M. Misuse and abuse of pregabalin. Current issues in prescription and over the counter medicine abuse, misuse and dependence [Internet]. Newcastle, UK: Society for the Study Addiction/ Liverpool John Moors University; 2020; [access in 2020 Aug 26]. Available from: https://www.addiction-ssa.org/images/uploads/Van_ HoutMC_Pregabalin_And_Gabapentin_1230_Fri_9_Nov_2018.pdf
• 27 Schifano F. Misuse and abuse of pregabalin and gabapentin: cause for concern? CNS Drugs. 2014 Apr;28:491-6.
• 28 Commission for Quality Control. Controlled drugs: pregabalin and gabapentin [Internet]. London, UK: Care Quality Commission; 2020; [access in 2020 Aug 26]. Available from: https://www.cqc.org.uk/ guidance-providers/adult-social-care/controlled-drugs-pregabalingabapentin
• 29 French JA, Kugler AR, Robbins JL, Knapp LE, Garofalo EA. Doseresponse trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology. 2003 May;60(10):1631-37.
• 30 Evoy KE, Morrison MD, Saklad SR. Abuse and misuse of pregabalin and gabapentin. Drugs. 2017 Mar;77(4):403-26.
• 31 Mayor S. Pregabalin and gabapentin become controlled drugs to cut deaths from misuse. BMJ. 2018 Oct;363:k4364.
• 32 Gahr M, Freudenmann RW, Hiemke C, Kölle MA. Pregabalin abuse and dependence in Germany: results from a database query. Eur J Clin Pharmacol. 2013 Jun;69(6):1335-42.
• 33 Hall TD, Shah S, Ng B, Feberwee HM, Dotchin L, Vandermost M, et al. Changes in mood, depression, and suicidal ideation after commencing pregabalin for neuropathic pain. Aust Fam Physician. 2014 Oct;43(10):705-8.
• 34 Joint Formulary Committee. British national formulary. London, UK: BMJ Publishing Group Ltd./Pharmaceutical Press; 2014.
• 35 Weintraub SJ. Diazepam in the treatment of moderate to severe alcohol withdrawal. CNS Drugs. 2017 Feb;31(2):87-95.
• 36 Calcaterra NE, Barrow JC. Classics in chemical neuroscience: diazepam (valium). ACS Chem Neurosci. 2014 Apr;5(4):253-60.
• 37 Kozyra E, Lau T. Medication strategies: switching, tapering, crossover, overmedication, drug-drug interactions, and discontinuation syndromes. In: Fenn HH, Hategan A, Bourgeois JA (eds.). Inpatient geriatric psychiatry. Cambridge: Springer Nature; 2019.
• 38 Sachdeva A, Choudhary M, Chandra M. Alcohol withdrawal syndrome: benzodiazepines and beyond. J Clin Diagn Res. 2015 Sep;9(9):VE01-VE07.
• 39 Rincón-Cortés M, Gagnon KG, Dollish HK, Grace AA. Diazepam reverses increased anxiety-like behavior, social behavior deficit, and dopamine dysregulation following withdrawal from acute amphetamine. Neuropsychopharmacol. 2018 Jun;43(12):2418-25.
• 40 Irish LA, Kline CE, Gunn HE, Buysse DJ, Hall MH. The role of sleep hygiene in promoting public health: a review of empirical evidence. Sleep Med Rev [Internet]. 2015 Aug; [cited 2020 Nov 18]; 22:23-36. Available from: https://www.sciencedirect.com/science/article/pii/S1087079214001002
• 41 Gong H, Ni CX, Liu YZ, Zhang Y, Su WJ, Lian YJ, et al. Mindfulness meditation for insomnia: a meta-analysis of randomized controlled trials. J Psychosom Res. 2016 Jul;89:1-6.
• 42 Manber R, Bernert RA, Suh S, Nowakowski S, Siebern AT, Ong JC. CBT for insomnia in patients with high and low depressive symptom severity: adherence and clinical outcomes. J Clin Sleep Med. 2011 Dec;7(6):645-52.
• 43 Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Groselj LD, Ellis JG, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017 Dec;26(6):675-700. DOI: https://doi.org/10.1111/ jsr.12594
• 44 Nagai N, Ayaki M, Yanagawa T, Hattori A, Negishi K, Mori T, et al. Suppression of blue light at night ameliorates metabolic abnormalities by controlling circadian rhythms. Invest Ophthalmol Vis Sci. 2019 Sep;60(12):3786-93.
• 45 O’Hagan JB, Khazova M, Price LLA. Low-energy light bulbs, computers, tablets and the blue light hazard. Eye (Lond). 2016 Feb;30(2):230-3.
• 46 Jniene A, Errguig L, El Hangouche AJ, Rkain H, Aboudrar S, El Ftouh M, et al. Perception of sleep disturbances due to bedtime use of blue light-emitting devices and its impact on habits and sleep quality among young medical students. Bio Med Res Int. 2019;2019:7012350.
• 47 Lawrenson JG, Hull CC, Downie LE. The effect of blue-light blocking spectacle lenses on visual performance, macular health and the sleepwake cycle: a systematic review of the literature. Ophthal Physiol Optics. 2017 Nov;37(6):644-54.
• 48 Spitzer RL, Kroenke K, Williams JBW, Löwe B. A brief measure for assessing generalized anxiety disorder. Arch Intern Med. 2006 May;166(10):1092-7.
• 49 Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007 Jul;4(7):28-37.
• 50 Morin C, Belleville G, Bélanger L, Ivers H. The insomnia severity index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011 May;34(5):601-8.
• 51 Gerring J. Case study research: principles and practices (strategies for social inquiry). 2nd ed. Cambridge: Cambridge University Press; 2017.
• 52 Chaudhary NS, Wong MM, Kolla BP, Kampman KM, Chakravorty S. The relationship between insomnia and the intensity of drinking in treatment-seeking individuals with alcohol dependence. Drug Alcohol Depend. 2020 Oct;215:108189.
• 53 Cross AL, Viswanath O, Sherman AI. Pregabalin. StatPearls [Internet]. 2021 Mar; [access in 2021 Jan 17]. Available from: https://www.ncbi. nlm.nih.gov/books/NBK470341/
• 54 Bonnet U, Scherbaum N. How addictive are gabapentin and pregabalin? A systematic review. Eur Neuropsychopharmacol. 2017 Dec;27(12):1185-215.