Abstract
Owing to its anxiolytic effects, pregabalin is used to treat many distressing symptoms, with various clinical observations supporting its potential benefits in cases of post-traumatic stress disorder (PTSD). However, a decade-long concern has been raised regarding the risk of patient misuse. A 27-year-old immigrant male self-treated with massive doses of pregabalin for at least 6 yr to alleviate his re-experiencing of the past war events he faced in his native country. PTSD and pregabalin-use disorder were diagnosed upon his arrival at our addiction care center. A controlled pregabalin withdrawal failed because the patient switched from this drug to alcohol and methadone available on the street. We therefore organized a hospitalization to provide a controlled methadone delivery and to begin pregabalin withdrawal, enabling thereafter the management of his care to focus on his PTSD. This case report invites clinicians to be cautious in prescribing pregabalin to patients suffering from PTSD, especially to at-risk populations such as migrants. Pregabalin has a positive effect on acute post-traumatic anxiety, but no long-term beneficial impact. As suggested by preclinical studies, pre-existing PTSD could potentiate the development of a pregabalin substance-use disorder.
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References
Al-Husseini, A., Van Hout, M. C., & Wazaify, M. (2018). Pregabalin misuse and abuse: A scoping review of extant literature. Journal of Drug Issues, 48(3), 356–376. https://doi.org/10.1177/0022042618759487.
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed). American Psychiatric Association.
Baniasadi, M., Hosseini, G., Fayyazi Bordbar, M. R., Ardani, A. R., & Toroghi, H. M. (2014). Effect of Pregabalin augmentation in treatment of patients with combat-related chronic posttraumatic stress disorder: A randomized controlled trial. Journal of Psychiatric Practice, 20(6), 419–427. https://doi.org/10.1097/01.pra.0000456590.12998.41.
Bonnet, U., & Scherbaum, N. (2017). How addictive are gabapentin and pregabalin? A systematic review. European Neuropsychopharmacology, 27(12), 1185–1215. https://doi.org/10.1016/j.euroneuro.2017.08.430.
Cairns, R., Schaffer, A. L., Ryan, N., Pearson, S., & Buckley, N. A. (2019). Rising pregabalin use and misuse in Australia: Trends in utilization and intentional poisonings. Addiction, 114(6), 1026–1034. https://doi.org/10.1111/add.14412.
Calandre, E. P., Rico-Villademoros, F., & Slim, M. (2016). Alpha-2-delta ligands, gabapentin, pregabalin and mirogabalin: A review of their clinical pharmacology and therapeutic use. Expert Review of Neurotherapeutics, 16(11), 1263–1277. https://doi.org/10.1080/14737175.2016.1202764.
Çıtak Ekici, Ö., Şahiner, V., Erzin, G., Ocak, D., Şahiner, Ş. Y., & Göka, E. (2019). Pregabalin abuse among patients with opioid use disorders may increase the severity of withdrawal symptoms: A single-center, case-control study. Psychiatry and Clinical Psychopharmacology, 29(4), 479–483. https://doi.org/10.1080/24750573.2019.1673946.
Coutens, B., Mouledous, L., Stella, M., Rampon, C., Lapeyre-Mestre, M., Roussin, A., Guiard, B. P., & Jouanjus, E. (2019). Lack of correlation between the activity of the mesolimbic dopaminergic system and the rewarding properties of pregabalin in mouse. Psychopharmacology, 236(7), 2069–2082. https://doi.org/10.1007/s00213-019-05198-z.
Evoy, K. E., Morrison, M. D., & Saklad, S. R. (2017). Abuse and misuse of pregabalin and gabapentin. Drugs, 77(4), 403–426. https://doi.org/10.1007/s40265-017-0700-x.
Fazel, M., Wheeler, J., & Danesh, J. (2005). Prevalence of serious mental disorder in 7000 refugees resettled in western countries: A systematic review. The Lancet, 365(9467), 1309–1314. https://doi.org/10.1016/S0140-6736(05)61027-6.
Fowler, M., Garza, T. H., Slater, T. M., Maani, C. V., & McGhee, L. L. (2012). The relationship between gabapentin and pregabalin and posttraumatic stress disorder in burned servicemembers. Journal of Burn Care & Research, 33(5), 612–618. https://doi.org/10.1097/BCR.0b013e31823dc710.
Gahr, M., Franke, B., Freudenmann, R. W., Kölle, M. A., & Schönfeldt-Lecuona, C. (2013). Concerns about pregabalin: Further experience with its potential of causing addictive behaviors. Journal of Addiction Medicine, 7(2), 147–149. https://doi.org/10.1097/ADM.0b013e3182872718.
Guina, J., Rossetter, S. R., DeRhodes, B. J., Nahhas, R. W., & Welton, R. S. (2015). Benzodiazepines for PTSD: A systematic review and meta-analysis. Journal of Psychiatric Practice, 21(4), 281–303. https://doi.org/10.1097/PRA.0000000000000091.
Häkkinen, M., Vuori, E., Kalso, E., Gergov, M., & Ojanperä, I. (2014). Profiles of pregabalin and gabapentin abuse by postmortem toxicology. Forensic Science International, 241, 1–6. https://doi.org/10.1016/j.forsciint.2014.04.028.
Harris, S., Dykxhoorn, J., Hollander, A.-C., Dalman, C., & Kirkbride, J. B. (2019). Substance use disorders in refugee and migrant groups in Sweden: A nationwide cohort study of 1.2 million people. PLoS Medicine, 16(11), e1002944. https://doi.org/10.1371/journal.pmed.1002944.
Horyniak, D., Melo, J. S., Farrell, R. M., Ojeda, V. D., & Strathdee, S. A. (2016). Epidemiology of substance use among forced migrants: A global systematic review. PLoS One, 11(7), e0159134. https://doi.org/10.1371/journal.pone.0159134.
Hoskins, M., Pearce, J., Bethell, A., Dankova, L., Barbui, C., Tol, W. A., van Ommeren, M., de Jong, J., Seedat, S., Chen, H., & Bisson, J. I. (2015). Pharmacotherapy for post-traumatic stress disorder: Systematic review and meta-analysis. British Journal of Psychiatry, 206(2), 93–100. https://doi.org/10.1192/bjp.bp.114.148551.
Jacobsen, L. K., Southwick, S. M., & Kosten, T. R. (2001). Substance use disorders in patients with posttraumatic stress disorder: A review of the literature. American Journal of Psychiatry, 158(8), 1184–1190. https://doi.org/10.1176/appi.ajp.158.8.1184.
Kavoussi, R. (2006). Pregabalin: From molecule to medicine. European Neuropsychopharmacology, 16, S128–S133. https://doi.org/10.1016/j.euroneuro.2006.04.005.
Kelmendi, B., Adams, T. G., Yarnell, S., Southwick, S., Abdallah, C. G., & Krystal, J. H. (2016). PTSD: From neurobiology to pharmacological treatments. European Journal of Psychotraumatology, 7(1), 31858. https://doi.org/10.3402/ejpt.v7.31858.
Lapeyre-Mestre, M., & Dupui, M. (2015). Drug abuse monitoring: Which pharmacoepidemiological resources at the European level? Therapies, 70(2), 157–165. https://doi.org/10.2515/therapie/2015010.
Logrip, M. L., Zorrilla, E. P., & Koob, G. F. (2012). Stress modulation of drug self-administration: Implications for addiction comorbidity with post-traumatic stress disorder. Neuropharmacology, 62(2), 552–564. https://doi.org/10.1016/j.neuropharm.2011.07.007.
Lyndon, A., Audrey, S., Wells, C., Burnell, E. S., Ingle, S., Hill, R., Hickman, M., & Henderson, G. (2017). Risk to heroin users of polydrug use of pregabalin or gabapentin: Risks in combining gabapentoids with heroin. Addiction, 112(9), 1580–1589. https://doi.org/10.1111/add.13843.
Mendell, J., Levy-Cooperman, N., Sellers, E., Vince, B., Kelsh, D., Lee, J., Warren, V., & Zahir, H. (2019). Abuse potential of mirogabalin in recreational polydrug users. Therapeutic Advances in Drug Safety, 10, 204209861983603. https://doi.org/10.1177/2042098619836032.
Merz, J., Schwarzer, G., & Gerger, H. (2019). Comparative efficacy and acceptability of pharmacological, psychotherapeutic, and combination treatments in adults with posttraumatic stress disorder: A network meta-analysis. JAMA Psychiatry, 76(9), 904. https://doi.org/10.1001/jamapsychiatry.2019.0951.
Nasca, C., Orlando, R., Marchiafava, M., Boldrini, P., Battaglia, G., Scaccianoce, S., Matrisciano, F., Pittaluga, A., & Nicoletti, F. (2013). Exposure to predator odor and resulting anxiety enhances the expression of the α2δ subunit of voltage-sensitive calcium channels in the amygdala. Journal of Neurochemistry, 125(5), 649–656. https://doi.org/10.1111/j.1471-4159.2012.07895.x.
Naveed, S., Faquih, A. E., & Chaudhary, A. M. D. (2018). Pregabalin-associated discontinuation symptoms: A case report. Cureus, 10(10), e:3425. https://doi.org/10.7759/cureus.3425.
Norman, S. B., Myers, U. S., Wilkins, K. C., Goldsmith, A. A., Hristova, V., Huang, Z., McCullough, K. C., & Robinson, S. K. (2012). Review of biological mechanisms and pharmacological treatments of comorbid PTSD and substance use disorder. Neuropharmacology, 62(2), 542–551. https://doi.org/10.1016/j.neuropharm.2011.04.032.
Pae, C.-U., Marks, D. M., Han, C., Masand, P. S., & Patkar, A. A. (2009). Pregabalin augmentation of antidepressants in patients with accident-related posttraumatic stress disorder: An open label pilot study. International Clinical Psychopharmacology, 24(1), 29–33. https://doi.org/10.1097/YIC.0b013e32831feea9.
Papazisis, G., & Kouvelas, D. (2015). The abuse liability of pregabalin: A pharmacological approach. Research and Advances in Psychiatry, 2(2), 75–80.
Paslakis, G., Gilles, M., & Deuschle, M. (2011). Pregabalin in the treatment of posttraumatic stress disorder: A case report. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35(4), 1160–1161. https://doi.org/10.1016/j.pnpbp.2011.02.005.
Pergolizzi, J. V., Taylor, R., Bisney, J., LeQuang, J. A., Coluzzi, F., & Gharibo, C. (2018). Gabapentinoid use disorder: Update for clinicians. EC Anesthesia, 4(8), 303–317.
Richter, K., Peter, L., Lehfeld, H., Zäske, H., Brar-Reissinger, S., & Niklewski, G. (2018). Prevalence of psychiatric diagnoses in asylum seekers with follow-up. BMC Psychiatry, 18(1). https://doi.org/10.1186/s12888-018-1783-y.
Riley, D. S., Barber, M. S., Kienle, G. S., Aronson, J. K., von Schoen-Angerer, T., Tugwell, P., Kiene, H., Helfand, M., Altman, D. G., Sox, H., Werthmann, P. G., Moher, D., Rison, R. A., Shamseer, L., Koch, C. A., Sun, G. H., Hanaway, P., Sudak, N. L., Kaszkin-Bettag, M., et al. (2017). CARE guidelines for case reports: Explanation and elaboration document. Journal of Clinical Epidemiology, 89, 218–235. https://doi.org/10.1016/j.jclinepi.2017.04.026.
Schifano, F., D’Offizi, S., Piccione, M., Corazza, O., Deluca, P., Davey, Z., Di Melchiorre, G., Di Furia, L., Farré, M., Flesland, L., Mannonen, M., Majava, A., Pagani, S., Peltoniemi, T., Siemann, H., Skutle, A., Torrens, M., Pezzolesi, C., van der Kreeft, P., & Scherbaum, N. (2011). Is there a recreational misuse potential for Pregabalin analysis of anecdotal online reports in comparison with related gabapentin and clonazepam data. Psychotherapy and Psychosomatics, 80(2), 118–122. https://doi.org/10.1159/000321079.
Schjerning, O., Rosenzweig, M., Pottegård, A., Damkier, P., & Nielsen, J. (2016). Abuse potential of Pregabalin: A systematic review. CNS Drugs, 30(1), 9–25. https://doi.org/10.1007/s40263-015-0303-6.
Schwan, S., Sundström, A., Stjernberg, E., Hallberg, E., & Hallberg, P. (2010). A signal for an abuse liability for pregabalin—Results from the Swedish spontaneous adverse drug reaction reporting system. European Journal of Clinical Pharmacology, 66(9), 947–953. https://doi.org/10.1007/s00228-010-0853-y.
Shorter, D., Hsieh, J., & Kosten, T. R. (2015). Pharmacologic management of comorbid post-traumatic stress disorder and addictions: Pharmacology of PTSD and SUD. The American Journal on Addictions, 24(8), 705–712. https://doi.org/10.1111/ajad.12306.
Strawn, J. R., Dowling, B. P., & Geracioti, T. D. (2008). Pregabalin treatment of posttraumatic stress disorder. Journal of Clinical Psychopharmacology, 28(5), 596–597. https://doi.org/10.1097/JCP.0b013e318184c8f2.
Taylor, C. P., Angelotti, T., & Fauman, E. (2007). Pharmacology and mechanism of action of pregabalin: The calcium channel α2–δ (alpha2–delta) subunit as a target for antiepileptic drug discovery. Epilepsy Research, 73(2), 137–150. https://doi.org/10.1016/j.eplepsyres.2006.09.008.
Valdivieso, D. A., Baughan, T. G., Canavati, U. M., Rey, A. M., Trotter, C. L., Burrell, D. R., Buonora, J. E., & Ceremuga, T. E. (2018). Effects of pregabalin on neurobehavior in an adult male rat model of PTSD. PLoS One, 13(12), e0209494. https://doi.org/10.1371/journal.pone.0209494.
Watts, B. V., Schnurr, P. P., Mayo, L., Young-Xu, Y., Weeks, W. B., & Friedman, M. J. (2013). Meta-analysis of the efficacy of treatments for posttraumatic stress disorder. The Journal of Clinical Psychiatry, 74(06), e541–e550. https://doi.org/10.4088/JCP.12r08225.
World Health Organization. (2018). Critical review report: Pregabalin. Expert Committee on Drug Dependence.
Zohar, J., Matar, M. A., Ifergane, G., Kaplan, Z., & Cohen, H. (2008). Brief post-stressor treatment with pregabalin in an animal model for PTSD: Short-term anxiolytic effects without long-term anxiogenic effect. European Neuropsychopharmacology, 18(9), 653–666. https://doi.org/10.1016/j.euroneuro.2008.04.009.
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GG and SS recruited the patient. GG, CP, MLM, LS, YH, and JS wrote the case report and conducted the literature search.
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This case was recorded anonymously in the French Addictovigilance database, according to French law (Articles R.5132–113 and R.5132–114).
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Galliot, G., Ponté, C., Schmitt, L. et al. Case Report: the Comorbidity of Pregabalin-Use Disorder and Post-Traumatic Stress Disorder: Clinical and Pharmacological Issues. Int J Ment Health Addiction 20, 152–161 (2022). https://doi.org/10.1007/s11469-020-00347-4
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DOI: https://doi.org/10.1007/s11469-020-00347-4