Pregabalin, popularly marketed as Lyrica, is a lipophilic analog of GABA (gamma amino-butyric acid) and is structurally similar to Gabapentin. It is currently indicated in the management of neuropathic pain, fibromyalgia, partial seizures, and epilepsy 4 . Pregabalin is believed to exert its pharmacological effects by acting on voltage gated calcium channels in the central nervous system inhibiting the influx of Ca 2+ into the nerves leading to a decrease in the release of excitatory neurotransmitters 1 .
In recent times, pregabalin has been classified as a Class C Schedule drug in the UK and a Schedule V drug in the United States 5 . This classification indicates that pregabalin cannot be purchased over the counter, and possession or sharing of the drug is only legal with a valid prescription.
Although pregabalin is currently not listed as a substance of abuse, recent studies have revealed that pregabalin has abuse potential, which is exacerbated in patients with a history of substance abuse disorder, as well as patients administered pregabalin along with opioids 2 . However, a recent case study demonstrated that at normal therapeutic doses of pregabalin for the management of neuropathic pain, patients developed symptoms such as shortness of breath, agitation, insomnia, and psychotic-like symptoms upon abrupt discontinuance 7 . This indicates that at normal therapeutic dose of pregabalin, patients with no history of substance abuse tend to develop dependence and withdrawal symptoms upon abrupt withdrawal. This is particularly significant, as most studies and reports of pregabalin abuse misuse the reason of substance abuse as a risk factor 6 . It should however be stated that while the sample size for the study was limited and no follow-up study has been conducted on it, it raises concern and points to a neglected area of research.
The reasons for the growing trend of pregabalin dependence and misuse are not clearly defined but contributing factors to the rising incidence includes ease of obtaining large quantities without a prescription with pregabalin prescriptions increasing by 5% between 2021 and 2022 in the UK 3 . Additionally, Off-label use and lack of thorough understanding about the abuse potential of pregabalin by both prescribers and patients alike 5 .
This places a clear responsibility on prescribers and healthcare professionals when prescribing pregabalin as patients may be unaware of the dependency potential of the medication. Additionally, since pregabalin has a soothing and calming effect, patients may be oblivious to the starting point of dependence, as most patients on pregabalin tend to take them daily. Prescribers and pharmacists should exercise more caution when prescribing pregabalin to patients already taking opioids as this exponentially increases the abuse potential of pregabalin 5 . Prescribers would need to take into cognizance history of substance abuse before prescribing pregabalin and necessitate routine monitoring of patients taking pregabalin to adequately monitor the onset of dependence as well as consider alternatives to pregabalin. This routine monitoring should involve constant medication review, preferably monthly for patients on long-term therapy and educating them on the signs of dependence. Furthermore, more intentional steps should be employed in tapering off patients on already high doses of pregabalin as opposed to abrupt discontinuation to prevent the development of withdrawal symptoms.
For patients without any history of substance abuse who need to be started on pregabalin therapy for management of chronic neuropathic pain, prescribers can start therapy by prescribing low doses of the medication with adequate patient counseling to ensure patients do not develop dependence.
Policymakers also have a role to play by establishing a patient registry solely for tracking use and outcome of pregabalin. More epidemiological surveys that monitor the prevalence rate of pregabalin abuse and dependence should be carried out to make informed decisions on policies to guide pregabalin prescription among prescribers.
References
1 Baidya, D. K., Agarwal, A., Khanna, P., & Arora, M. K. (2011). Pregabalin in acute and chronic pain. Journal of Anaesthesiology Clinical Pharmacology , 27 (3). https://journals.lww.com/joacp/fulltext/2011/27030/pregabalin_in_acute_and_chronic_pain.3.aspx
2 Bonnet, U., & Scherbaum, N. (2017). How addictive are gabapentin and pregabalin? A systematic review. European Neuropsychopharmacology , 27 (12), 1185-1215. https://doi.org/https://doi.org/10.1016/j.euroneuro.2017.08.430
3 Care Quality Commission. (2022). National trends in the prescribing of controlled drugs . Retrieved 13/10/2024 from https://www.cqc.org.uk/publications/safer-management-controlled-drugs-annual-update-2022/national-trends-prescribing-controlled-drugs
4 Chiappini, S., & Schifano, F. (2016). A Decade of Gabapentinoid Misuse: An Analysis of the European Medicines Agency’s ‘Suspected Adverse Drug Reactions’ Database. CNS Drugs , 30 (7), 647-654. https://doi.org/10.1007/s40263-016-0359-y
5 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
6 Grosshans, M., Lemenager, T., Vollmert, C., Kaemmerer, N., Schreiner, R., Mutschler, J., Wagner, X., Kiefer, F., & Hermann, D. (2013). Pregabalin abuse among opiate addicted patients. European Journal of Clinical Pharmacology , 69 (12), 2021-2025. https://doi.org/10.1007/s00228-013-1578-5
7 Ishikawa, H., Takeshima, M., Ishikawa, H., Ayabe, N., Ohta, H., & Mishima, K. (2021). Pregabalin withdrawal in patients without psychiatric disorders taking a regular dose of pregabalin: A case series and literature review. Neuropsychopharmacology Reports , 41 (3), 434-439. https://doi.org/https://doi.org/10.1002/npr2.12195