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CASE REPORT
Year : 2020  |  Volume : 68  |  Issue : 6  |  Page : 1469--1471

A Case of Pregabalin-Induced Parkinsonism

Buse Cagla ARI1, Fusun Mayda Domac1, Gulay Ozgen Kenangil2,  
1 University of Health Sciences, Erenkoy Mental Health and Neurological Disorders Research and Training Hospital, Neurology Department, Istanbul-, Turkey
2 Bahcesehir University Medical Faculty, Neurology Department, Istanbul –, Turkey

Correspondence Address:
Dr. Buse Cagla ARI
Erenkoy Ruh ve Sinir Egitim ve Arastirma Hastanesi Noroloji Yatan Hasta Servisi Sinan Ercan Cad. No: 29 34744 Kazasker – Kadikoy/Istanbul
Turkey

Abstract

Drug-induced parkinsonism is the second common movement disorder after Parkinson's disease. It occurs due to the use of not only neuroleptics but also some other medications as pregabalin. Pregabalin is an antiepileptic drug and a structural analog of gamma-aminobutyric acid (GABA), and its use decreases the release of several neurotransmitters. In this case report, we present a 53-year-old female patient with the signs of parkinsonism following pregabalin treatment. Drug-induced parkinsonism was diagnosed based on the clinical features, investigations, and resolution of the complaints. The symptoms relieved after the treatment stopped at a follow-up of 10 days. Due to the rare report of pregabalin-induced parkinsonism, we aim to enhance clinicians' awareness of pregabalin's probable side effects.



How to cite this article:
ARI BC, Domac FM, Kenangil GO. A Case of Pregabalin-Induced Parkinsonism.Neurol India 2020;68:1469-1471


How to cite this URL:
ARI BC, Domac FM, Kenangil GO. A Case of Pregabalin-Induced Parkinsonism. Neurol India [serial online] 2020 [cited 2021 Mar 6 ];68:1469-1471
Available from: https://www.neurologyindia.com/text.asp?2020/68/6/1469/304071


Full Text



Parkinsonism is a neurodegenerative condition that occurs due to the progressive alpha-synuclein or tau deposition in the basal ganglia.[1] The most common form is Parkinson's disease (PD), and the frequency of drug-induced parkinsonism comes secondly. The clinical features of drug-induced parkinsonism (DIP) are widespread and similar to PD symptoms; therefore, it is occasionally misdiagnosed as PD.[1],[2],[3] DIP is characterized by bilateral and symmetrical parkinsonism symptoms. Bradykinesia and rigidity are prominent, and neurological deficits are severe than PD. Age, female gender, drug usage, and genetic factors might be considered as risk factors.[2] The exact prevalence remains unknown.[3] This condition occurs not just with the use of neuroleptics but also with other drugs like serotonin reuptake inhibitors (SSRIs), antipsychotic drugs, anti-dopaminergic drugs, lithium, levosulpiride, calcium channel blockers, and antiepileptics such as valproic acid. Pregabalin is an antiepileptic drug commonly prescribed for epileptic seizures, neuropathic pain, and postherpetic neuralgia. It is hypothesized that pregabalin administration may decrease several neurotransmitters; thus, parkinsonism occurs as a side effect but is unclear.[1],[4],[5],[6] According to what we know so far, there have been insufficient reports about pregabalin-induced parkinsonism. Since there is a lack of information about this extraordinarily infrequent side effect and the mechanism is still unknown, herein, we desired to present our case.

 Case Report



A 53-year-old female patient presented with the symptoms of hoarseness, dysarthria, dizziness, decelerated movements, and ambulatory exertion one week later taking pregabalin (150 mg/day) treatment due to the pain of fibromyalgia. After increasing the daily dosage to 300 mg/day, her symptoms had got worsened. Her neurological examination revealed bradymimia, bradykinesia, the rigidity of bilateral extremities, and a decrease in the natural swing arms while walking. Her Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score was increased to 23. She also suffered from migraine, familial Mediterranean fever, and hypertension. She was receiving irbesartan and thiazide (300/12.5 mg) daily as a treatment for 2 years. She did not take any drug recently that might cause parkinsonism, and she had no family history of any movement disorders. Her complete blood counts, hemoglobin A1c level, hematology parameters, and 24-h urine sample were normal. Her cranial magnetic resonance imaging (MRI) and computerized tomography (CT) did not detect any abnormality [Figure 1] and [Figure 2]. Dopamine transporter imaging (DAT) could not be performed due to its absence in our hospital. The ophthalmological examination was evaluated and did not detect any abnormality. In light of these features, pregabalin treatment was withdrawn initially, and we started levodopa/benserazide (100/25 mg) three times daily for 3 months. At the follow-up of 10 days, her findings recovered except bradymimia. After 3 months of levodopa/benserazide treatment, we observed that all clinical features had been recovered. Her MDS-UPDRS part III score was decreased to baseline. According to the clinical findings and the resolution of her complaints after discontinuing the pregabalin, she was diagnosed as pregabalin-induced parkinsonism.{Figure 1}{Figure 2}

 Discussion



This study is to describe a patient that suffers from parkinsonism that occurred after the use of pregabalin 1-month before her administration to the hospital. Even though it was in our knowledge that she was taking irbesartan/thiazide medication, we ruled out its probability of developing DIP due to long-term administration. A considerable amount of literature has been published and stated that neither angiotensin II receptor blockers (ARBs) nor diuretics have the ability to develop DIP. Until now, an interaction between pregabalin, irbesartan, orthiazide has never been reported. Her symptoms initiated with the administration of pregabalin and resolved in 3 weeks after its discontinuation. In light of these features, it could be concluded that parkinsonism is associated with pregabalin treatment.

Pregabalin binds to the alpha-2-delta subunit of L-type voltage-dependent calcium channels (VDCC). The exact pathophysiology that underlies pregabalin-induced parkinsonism remains unknown due to the lack of study. It might be presumed that pregabalin might affect presynaptic regulation, deplete glutamate, acetylcholine, substance P, noradrenaline, and dopamine levels by blocking D2 receptors in the neocortex, amygdala, striatum, and cerebellum.[5],[7],[8] It is challenging to establish, which neurotransmitters could be determined as responsible ones.[5],[9] In the literature, there are different hypotheses about its mechanism to develop DIP. One of them is, even though there is a lack of information, pregabalin may maintain dopaminergic transmission and reduce dopamine release.[10] According to another point of view, its effect on reducing the release of substance P alters the GABAergic network on globus pallidus by acting through neurokinin 1 (NK1) receptors; thus, parkinsonism reveals.[5],[7],[11] The only information in our knowledge so far is the higher doses of administration cause adverse effects.[12]

The capability of developing parkinsonism of cinnarizine and flunarizine has long been known as two of the most administrated VDCC agents, even on lower doses. Although the pathophysiology remains vague, researchers believe that some mechanisms put forward of them causing DIP. The first one is the direct blocking of postsynaptic dopamine D2 receptors, the second one is the decrease in presynaptic dopamine release by blocking the calcium admission, and the last one is the ultimate dopaminergic neuron decease through the mitochondrial respiratory chain.[8],[11],[13] One of the issues that emerge from these findings is that since pregabalin is classified as a VDCC, it might be assumed that this drug might have a similar mechanism of cinnarizine and flunarizine for developing DIP. Nevertheless, this is just an estimation, and further investigations are required to bring in to open.

 Conclusion



In conclusion, this report's primary goal is to increase the awareness of pregabalin as a potential drug to develop parkinsonism. This case reveals the need for further researches to establish its adverse effects.

Acknowledgements

We obtained the patient's informed consent before writing this case report.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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