Parkinsonism Associated with Gabapentinoid Drugs: A Pharmacoepidemiologic Study

Pacheco, Tatiana; Montastruc, François; Rousseau, Vanessa; Chebane, Leila; Lapeyre‐Mestre, Maryse; Renoux, Christel; Montastruc, Jean‐Louis

doi:10.1002/mds.27876

Cited by 11 publications

(12 citation statements)

References 33 publications

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“…For the years 1999 and 2019, a total of 46 reports containing 305 cases who developed MDs after the use of PGB from 17 different countries were reported [ Table 1 ]. [ 2 3 10 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 ] The origin was North American in 196, European in 68, Asian in 40, and South American in 1. The MDs associated with PGB found were as follows: 184 patients with ataxia, 61 with tremors, 39 with MCL, 8 with parkinsonism, 1 with restless legs syndrome, 1 with dystonia, 1 with dyskinesia, and 1 with akathisia.…”

Section: Resultsmentioning

confidence: 99%

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Pregabalin-associated movement disorders: A literature review

Rissardo

Caprara

2020

Brain Circ

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Central nervous system adverse effects are commonly reported with pregabalin (PGB). On the other hand, movement disorders (MDs) associated with this drug were rarely described. However, their occurrence could significantly affect the quality of life of PGB users. This literature review aims to evaluate the clinical epidemiological profile, pathological mechanisms, and management of PGB-associated MDs. Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 46 reports containing 305 cases from 17 countries were assessed. The MDs encountered were as follows: 184 individuals with ataxia, 61 with tremors, 39 with myoclonus, 8 with parkinsonism, 1 with restless legs syndrome, 1 with dystonia, 1 with dyskinesia, and 1 with akathisia. The mean age was 62 years (range: 23–94). The male sex was slightly predominant with 54.34%. The mean PGB dose when the MD occurred was 238 mg, and neuropathic pain was the most common indication of PGB. The time from PGB start to MD was < 1 month at 75%. The time from PGB withdrawal to recovery was < 1 week at 77%. All the individuals where the follow-up was reported had a full recovery. The most common management was PGB withdrawal. In the literature, the majority of the cases did not report information about timeline events, neurological examination details, or electrodiagnostic studies. The best management for all MDs is probably PGB withdrawal. If the patient is on dialysis program, perhaps an increased number of sessions will decrease recovery time. Furthermore, the addition of a benzodiazepine could accelerate recovery.

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Section: Resultsmentioning

confidence: 99%

“…Three articles did not report the number of patients, but they observed MCL[ 39 54 ] and parkinsonism. [ 49 ]…”

Section: Resultsmentioning

confidence: 99%

Pregabalin-associated movement disorders: A literature review

Rissardo

Caprara

2020

Brain Circ

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“…We have read "Parkinsonism associated with gabapentinoid drugs: a pharmacoepidemiologic study" by Pacheco-Paez and colleagues with great interest. 1 As the use of gabapentinoid drugs increases, any information on their possible long-term side effects is warranted. Based on the VigiBase database, the researchers concluded that both gabapentin (GBP) and pregabalin (PRG) have 2.16 to 2.43 times higher reporting odds ratios (RORs) for developing parkinsonism than nonusers, indicating possible adverse reactions.…”

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confidence: 99%

“…Dávid Pintér, MD, 1 József Janszky, MD, DSc, 2,3 and Norbert Kovács, MD, DSc We read with interest the comments by Pinter and colleagues about our article in which we suggested an association between exposure to gabapentinoids (gabapentin, pregabalin) and the occurrence of parkinsonism. 1 The authors discussed several points.…”

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Comment on “Parkinsonism Associated with Gabapentinoid Drugs: A Pharmacoepidemiologic Study”

Pintér

Janszky²,

Kovács³

2020

Movement Disorders

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We have read "Parkinsonism associated with gabapentinoid drugs: a pharmacoepidemiologic study" by Pacheco-Paez and colleagues with great interest. 1 As the use of gabapentinoid drugs increases, any information on their possible long-term side effects is warranted. Based on the VigiBase database, the researchers concluded that both gabapentin (GBP) and pregabalin (PRG) have 2.16 to 2.43 times higher reporting odds ratios (RORs) for developing parkinsonism than nonusers, indicating possible adverse reactions.However, in our opinion, the lack of numerous important factors (e.g., age, indications, and comorbidities) prevents from identifying any causative relationships between gabapentinoid usage and reported parkinsonism.While GBP has numerous on-label indications (e.g., epilepsy, peripheral neuropathic pain caused by diabetic neuropathy, and postherpetic neuralgia), it may be used in restless legs syndrome (RLS), essential tremor (ET), and central-or spasticity-related pain efficiently. Besides, PRG has an indication for generalized anxiety and the off-label use for chronic low-back pain. Gabapentinoid drugs are more frequently prescribed in patients with older age, higher comorbidity index, and diabetes. 2 Reimbursement and costs can also have an impact on the use of these drugs. Based on the publicly available Hungarian National Health Insurance Fund data, the vast majority of real-life gabapentinoid usage is associated with diabetic neuropathic pain (72.2% and 89.5% for GBP and PRG, respectively).The interpretation of the VigiBase data without relevant clinical data is very limited because some of the gabapentinoid indications (e.g., type 2 diabetes mellitus [T2DM], RLS, or ET) may be associated with higher risks for developing parkinsonism. 3,4 For example, T2DM may increase the risk by 41%. 4 Therefore, the underlying T2DM supposedly is not a negligible factor behind the increased RORs observed with gabapentinoid usage.To compensate for this weakness and assess "the robustness" of their findings, the researchers made some efforts. They tried to exclude cases where other drugs capable of inducing parkinsonism were used, but some concomitant medications (e.g., trimetazidine 5 ) were not taken into consideration. The reported risks for parkinsonism concerning amitriptyline and duloxetine, drugs having similar indications with gabapentinoids, were also compared. Although amitriptyline might have similar indications for neuropathic pain, it has numerous contraindications, mainly attributed to cholinergic side effects and significantly more pharmacological interactions, limiting its use in T2DM and the elderly. Therefore, we believe that the comparison between gabapentinoids versus duloxetine was more feasible. Table 2 shows that GBP and PRG usage is associated with 0.91 (95% confidence interval [CI]: 0.86-0.96) and 1.15 (95% CI: 1.09-1.22) higher risks for reported parkinsonism compared to duloxetine users. Considering that gabapentinoids are more frequently prescribed in the elderly, 2 where development of parkins...

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Centre (UMC), which provided and gave permission to use the data analyzed in the study. The authors are indebted to the National Pharmacovigilance Centers that contributed data. The opinions and conclusions in this study are not necessarily those of the various centers or of the WHO (World Health Organization) or ANSM (Agence Nationale de Sécurité du Médicament et des produits de santé, France).

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Parkinsonism Associated with Gabapentinoid Drugs: A Pharmacoepidemiologic Study

Cited by 11 publications

References 33 publications

Pregabalin-associated movement disorders: A literature review

Pregabalin-associated movement disorders: A literature review

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