Patterns of gabapentin and pregabalin use and misuse: Results of a population‐based cohort study in France

Abstract

Aims: The aim of this study was to assess the use and factors associated with the misuse of gabapentin and pregabalin in the general French population, through a cohort study in the EGB (General Sample of Beneficiaries), a national representative sample of the French general population.Methods: New users of gabapentin and pregabalin were identified from June 2006 to December 2014, and new users of duloxetine served as control group. Misuse was defined as a use of higher daily doses than recommended. Cox proportional hazard regression models were performed to identify associated factors of misuse.Results: Misuse was more frequent in the 8692 new users of pregabalin (12.8%) than in the 1963 gabapentin (6.6%) or the 3214 duloxetine new users (9.7%) (P < 0.001). Factors associated with misuse were pregabalin (hazard ratio [HR] 1.48; 95% confidence interval [CI] [1.29-1.69]), age (HR [18-45] versus > 70 years 1.98 [1.70-2.31] and HR [58-70] versus > 70 years 1.25 [1.06-1.47]), multiple prescribers (HR 2 or 3 versus 1 prescriber 1.29 [1.15-1.45]; HR 4 or more versus 1 prescriber 1.54 [1.30-1.83]), cancer (1.28 [1.11-1.47]), multiple sclerosis (1.53 [1.07-2.18]), neuropathy (1.85 [1.19-2.89]), depression (1.26 [1.07-1.49]) and methadone (2.61 [1. 16-5.84]). After this first episode of drug misuse, 11.6% of gabapentin and 10.7% of pregabalin misusers developed a primary addiction.Conclusion: In a cohort of new users, misuse is more likely to occur in new users of pregabalin, with different associated factors of misuse compared to gabapentin and duloxetine. Health professionals and prescribers must be aware of this misuse potential, which could lead to abuse and dependence.

Parkinsonism Associated with Gabapentinoid Drugs: A Pharmacoepidemiologic Study

“…First, to minimize potential confounding, we excluded reports that mentioned: (1) drugs known to induce parkinsonism (dopamine antagonists like antipsychotics, flunarizine, cinnarizine, metoclopramide, metopimazine, droperidol) because they could be coreported with gabapentinoids and distort the signal, and (2) dopaminergic antiparkinsonian drugs because gabapentinoids are frequently prescribed in Parkinson's disease (PD). Second, we assessed the risk of reporting “parkinsonism” with gabapentinoids compared with amitriptyline and duloxetine, drugs used for the main gabapentinoid indication, neuropathic pain . In this sensitivity analysis, RORs were adjusted for age, sex, year of report, continent of report, notifier type (health professional), and completeness score (>0.8), a tool developed by UMC to measure the amount of clinically relevant information in 1 report .…”

“…Second, we assessed the risk of reporting "parkinsonism" with gabapentinoids compared with amitriptyline and duloxetine, drugs used for the main gabapentinoid indication, neuropathic pain. 3 In this sensitivity analysis, RORs were adjusted for age, sex, year of report, continent of report, notifier type (health professional), and completeness score (>0.8), a tool developed by UMC to measure the amount of clinically relevant information in 1 report. 12 If there were missing data on adjustment variables, unadjusted RORs were also calculated for cases without missing data on the set of adjustment variables.…”

“…1,2 Compelling evidence indicates that oxidative stress and neuroinflammation play central roles in the pathophysiology of PD. [3][4][5][6] These processes are critically modulated by the transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of cellular defence.…”

“…Gabapentinoids, such as gabapentin and pregabalin, are indicated in neuropathic pain and epilepsy. Recent US and European data have shown that their use tripled during the last decade, and there has been a high level of off‐label prescriptions and misuse . Although side effects, such as somnolence, dizziness, and ataxia, are usually mild, long‐term adverse effects are unknown.…”

“…Recent US and European data have shown that their use tripled during the last decade, and there has been a high level of offlabel prescriptions and misuse. [1][2][3] Although side effects, such as somnolence, dizziness, and ataxia, are usually mild, long-term adverse effects are unknown. Their pharmacodynamic mechanisms are complex and poorly understood, which should lead to vigilance in clinical practice.…”