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HOME > J Mov Disord > Volume 17(3); 2024 > Article
Letter to the editor
Dopamine Dysregulation Syndrome Presenting as Overuse of Mucuna pruriens Levodopa Supplement
David O. Sohutskay1,2corresp_iconorcid, Rachel M. Suen2orcid, Farwa Ali1orcid, David J. Rosenman2orcid
Journal of Movement Disorders 2024;17(3):357-359.
DOI: https://doi.org/10.14802/jmd.24067
Published online: May 21, 2024

1Department of Neurology, Mayo Clinic, Rochester, MN, USA

2Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

Corresponding author: David O. Sohutskay, MD, PhD Departments of Neurology and Internal Medicine, Mayo Clinic, 200 1st Street SW, Rochester, MN 55902, USA / Tel: +1-507-284-2511 / Fax: +1-440-760-6596 / E-mail: Sohutskay.David@mayo.edu
• Received: March 16, 2024   • Revised: May 15, 2024   • Accepted: May 18, 2024

Copyright © 2024 The Korean Movement Disorder Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Dear Editor,
Mucuna pruriens, the velvet bean, is an herbal supplement that is sold by many online retailers and supermarkets. The raw plant contains approximately 5% levodopa by volume, and commercial preparations typically contain 100 mg or more of levodopa per capsule. Given this fact, it is unsurprising that at appropriate doses, Mucuna pruriens supplementation has in some studies shown efficacy comparable to that of pharmaceutical-grade preparations such as immediate release (IR) or extended release (ER) carbidopa/levodopa in the treatment of Parkinson’s disease (PD) [1]. Dopamine dysregulation syndrome (DDS) is a rare but life-altering complication of dopamine replacement therapy (DRT) that can be defined by a pattern of compulsive overuse of DRT despite the development of negative side effects such as dyskinesias, emotional dysregulation, and psychosis [2]. DDS may be present along with other impulse control disorders (ICDs), such as hypersexuality, excessive gambling or shopping, or repetitive non-goal-directed behaviors referred to as punding. Risk factors for DDS include length of DRT and exposure to pulsatile dopamine [2]. Here, we report the case of a patient who developed DDS with excessive use of Mucuna pruriens levodopa supplements, precipitating episodes of agitation, psychosis, and dyskinesia.
The present patient developed a unilateral tremor at age 47 and was subsequently diagnosed with idiopathic PD by her neurologist. After a discussion of the efficacy and side effects of levodopa and dopamine agonists, in which she also expressed a preference for the most effective long-term therapy, she was initiated on carbidopa/levodopa IR. However, she self-discontinued the medication due to nausea, anxiety, and reported pruritis. As her PD symptoms were initially mild, she continued without medication for several years (Figure 1). As her tremor progressed and she experienced further difficulties with gait and rigidity, she reinitiated treatment at age 52. At age 54, she began using Mucuna pruriens as a means of augmenting her DRT. She attributed her use of these supplements to interest in a more natural means of treating the disease.
At age 55, the patient first experienced a brief episode of hallucinations and paranoia that was thought to be related to her DRT. The symptoms resolved after a brief hospitalization for observation, and she was discharged home. She was hospitalized once again at age 57 with dyskinesias, and her family noted that she was taking her medications, including the Mucuna pruriens supplement, more frequently than recommended. Evaluation by a movement disorder specialist noted a Unified Parkinson’s Disease Rating Scale Part III “on” score of 3 and an “off” score of 34. Carbidopa/levodopa IR was discontinued at this time in favor of carbidopa/levodopa ER together with the patient’s preferred choice of the Mucuna pruriens; however, she was rehospitalized at age 58 with vomiting and agitation secondary to suspected medication overuse and again at age 59 with a psychotic episode noted to have features of Othello syndrome (delusional jealousy). A cognitive screen was not suggestive of severe impairment, with 31/38 points on the Kokmen mental status examination and 4 points lost on motor tasks. Her medications were recommended to be reduced, but at an outpatient follow-up visit, she was noted by her family to be hiding her medication and taking extra doses, suggesting the development of DDS. Finally, she was brought to the emergency department by her husband due to acute agitation after consuming approximately 100 capsules of her Mucuna pruriens supplement over the course of 2 days. She was noted to be restless, with pressured speech and made contradictory and odd statements. The patient was hospitalized for observation. Overnight, she began to demonstrate bradykinesia, tremor, hypomimia, and paucity of speech.
The patient reported that in addition to receiving carbidopa/levodopa ER twice daily and applying a rotigotine patch once daily, she took 3–5 capsules of Mucuna pruriens as needed throughout the day, according to her symptoms. She estimated taking this dose of Mucuna pruriens approximately every 3 hours. Her husband noted that she had acquired the supplement from an internet-based supplier without his knowledge, as he had previously suggested that she refrain from consuming the supplement. He described her taking large quantities, triggering episodes of agitation, including insomnia, characterized by pacing throughout the night and working purposelessly on various household tasks, such as cleaning or cooking. The patient lacked insight throughout her admission, and ultimately, a decision was made by the family to pursue long-term care at an adult foster home. She was transitioned off the supplement and onto a stable regimen consisting solely of carbidopa/levodopa ER capsules.
Some patients have expressed fear and distrust of standard pharmaceutical treatments for PD, so-called “levodopa phobia.” [3] Alternative practitioners have proposed Mucuna pruriens as a treatment for parkinsonism, which may be more palatable to some patients despite containing the same primary active ingredient [4]. The levodopa content of Mucuna pruriens extracts is quite variable, and the measured amounts can range from nearly negligible to more than twice the stated dose [5]. DRT is associated with side effects, including dyskinesias, ICDs, and psychosis. The pathophysiology of ICDs is complex but linked to changes in striatal dopamine signaling induced by exposure to pulsatile dopamine. It is well-established that pulsatile dopamine is a risk factor for the development of dyskinesias, and the use of levodopa alone without an inhibitor of aromatic amino acid decarboxylase may lead to more treatment-related motor fluctuations [6]. Currently, the evidence regarding the tolerability of Mucuna pruriens versus pharmaceutical preparations is limited and mixed [1].
Here, we describe a patient who was hospitalized several times with side effects of DRT that included Mucuna pruriens levodopa supplements. The patient lacked insight into her condition and required oversight of her medication regimen. There is a high rate of relapse in patients with DDS. Although the potential for hallucinations and psychosis secondary to an acute overdose of Mucuna pruriens has been well documented [7], this is the first case report describing DDS presenting as excessive use of commercial levodopa supplements in a patient with PD. This report highlights the potential risks of a widely available herbal supplement used by patients as an adjunctive treatment for parkinsonism. It is important for neurologists to be aware of these herbal supplements and understand the potential interactions they may have with prescribed medication.

Ethics Statement

The Mayo Clinic Institutional Review Board (IRB) acknowledges that the report does not require IRB review, the requirement of informed consent was waived by institutional policy as the report does not include identifying information or images. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Author Contributions

Conceptualization: David O. Sohutskay. Writing—original draft: David O. Sohutskay. Writing—review & editing: Rachel M. Suen, Farwa Ali, David J. Rosenman.

None
Figure 1.
Timeline of events. The patient was diagnosed with PD at age 47. She began DRT at age 52 with the addition of the Mucuna pruriens supplement two years after her diagnosis. At age 57, this supplement became the bulk of her DRT despite ongoing recommendations to reduce its use after repeated hospitalizations. IR, immediate release; ER, extended release; PD, Parkinson’s disease; DRT, dopamine replacement therapy.
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  • 1. Cilia R, Laguna J, Cassani E, Cereda E, Pozzi NG, Isaias IU, et al. Mucuna pruriens in Parkinson disease: a double-blind, randomized, controlled, crossover study. Neurology 2017;89:432–438.ArticlePubMedPMC
  • 2. O’Sullivan SS, Evans AH, Lees AJ. Dopamine dysregulation syndrome: an overview of its epidemiology, mechanisms and management. CNS Drugs 2009;23:157–170.ArticlePubMed
  • 3. Titova N, Levin O, Katunina E, Ray Chaudhuri K. ‘Levodopa phobia’: a review of a not uncommon and consequential phenomenon. NPJ Parkinsons Dis 2018;4:31.ArticlePubMedPMCPDF
  • 4. Manyam BV. Paralysis agitans and levodopa in “Ayurveda”: ancient Indian medical treatise. Mov Disord 1990;5:47–48.ArticlePubMed
  • 5. Cohen PA, Avula B, Katragunta K, Khan I. Levodopa content of Mucuna pruriens supplements in the NIH dietary supplement label database. JAMA Neurol 2022;79:1085–1086.ArticlePubMedPMC
  • 6. Jenner P. Avoidance of dyskinesia: preclinical evidence for continuous dopaminergic stimulation. Neurology 2004;62(1 Suppl 1):S47–S55.PubMed
  • 7. Infante ME, Perez AM, Simao MR, Manda F, Baquete EF, Fernandes AM, et al. Outbreak of acute toxic psychosis attributed to Mucuna pruriens. Lancet 1990;336:1129.Article

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      Dopamine Dysregulation Syndrome Presenting as Overuse of Mucuna pruriens Levodopa Supplement
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      Figure 1. Timeline of events. The patient was diagnosed with PD at age 47. She began DRT at age 52 with the addition of the Mucuna pruriens supplement two years after her diagnosis. At age 57, this supplement became the bulk of her DRT despite ongoing recommendations to reduce its use after repeated hospitalizations. IR, immediate release; ER, extended release; PD, Parkinson’s disease; DRT, dopamine replacement therapy.
      Dopamine Dysregulation Syndrome Presenting as Overuse of Mucuna pruriens Levodopa Supplement

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