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Down-titration of levodopa complicated by catatonia

D. Newbold, . (New York, USA)

Meeting: 2025 International Congress

Keywords: Catatonia, Dopamine dysregulation syndrome, Levodopa(L-dopa)

Category: Parkinson’s Disease: Pharmacology and Medical Management

Objective: Provide evidence that reductions in levodopa can trigger catatonia

Background: Dopamine dysregulation syndrome (DDS) occurs when patients crave and self-up-titrate levodopa, often leading to impulse control disorders and psychosis [1, 2]. Down-titrating dopaminergic medications is essential for management [3-5], but there is little guidance about how to taper levodopa or what complications might result [6, 7]. Abrupt cessation of levodopa can produce Parkinsonism-hyperreflexia syndrome (PHS) [8-13], which is resembles neuroleptic malignant syndrome (NMS) and involves stupor, muscle rigidity, and autonomic instability. Catatonia is characterized by stupor, ambitendency, waxy flexibility, and catalepsy. Severe cases can involve autonomic instability, hyperthermia and rhabdomyolysis, a state termed “malignant catatonia,” which is almost identical to NMS [14, 15]. Thus, a mild form of PHS following down-titration of levodopa might present as catatonia, but we could not find any existing literature warning of this complication.

Method: N/A (case report)

Results: A 68-year-old man with Parkinsonism and mild cognitive impairment due to Lewy body disease was hospitalized for the management of DDS. He had been prescribed a total 1.8 grams of levodopa daily but had self-increased to over 3 grams daily, leading to subacute cognitive decline, repetitive and purposeless behaviors, and hypersexuality making his family unable to care for him. His initial exam was notable for mild Parkinsonism, pressured speech, paranoid delusions, and responses to internal stimuli. Given concern for DDS complicated by drug-induced mania and psychosis, his levodopa was rapidly down-titrated to a total of 1.8 grams daily. His Parkinsonian motor symptoms remained well controlled but he quickly developed worsening dysarthria and hyperactive delirium, soon followed by behavioral withdrawal, mutism, grimacing, posturing, echolalia, and cataplexy. He showed a dramatic response to lorazepam, but could not tolerate standing lorazepam due to sedation. He underwent 6 rounds of electroconvulsive therapy, ultimately leading to complete resolution of all catatonic features.

Conclusion: Catatonia may be an inherent and under-recognized risk of levodopa down-titration. Clinicians must maintain a high index of suspicion, as prompt recognition is crucial to prevent death and early signs may be mistaken for worsening Parkinsonism or delirium.

References: References
1. Giovannoni, G., et al., Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies. J Neurol Neurosurg Psychiatry, 2000. 68(4): p. 423-8.
2. Pezzella, F.R., et al., Prevalence and clinical features of hedonistic homeostatic dysregulation in Parkinson’s disease. Mov Disord, 2005. 20(1): p. 77-81.
3. Cilia, R., et al., Dopamine dysregulation syndrome in Parkinson’s disease: from clinical and neuropsychological characterisation to management and long-term outcome. J Neurol Neurosurg Psychiatry, 2014. 85(3): p. 311-8.
4. Warren, N., et al., Dopamine dysregulation syndrome in Parkinson’s disease: a systematic review of published cases. J Neurol Neurosurg Psychiatry, 2017. 88(12): p. 1060-1064.
5. Barbosa, P., et al., The Outcome of Dopamine Dysregulation Syndrome in Parkinson’s Disease: A Retrospective Postmortem Study. Mov Disord Clin Pract, 2018. 5(5): p. 519-522.
6. Koschel, J., et al., Implications of dopaminergic medication withdrawal in Parkinson’s disease. J Neural Transm (Vienna), 2022. 129(9): p. 1169-1178.
7. Debove, I., et al., Management of Impulse Control and Related Disorders in Parkinson’s Disease: An Expert Consensus. Mov Disord, 2024. 39(2): p. 235-248.
8. Toru, M., et al., Neuroleptic malignant syndrome-like state following a withdrawal of antiparkinsonian drugs. J Nerv Ment Dis, 1981. 169(5): p. 324-7.
9. Friedman, J.H., S.S. Feinberg, and R.G. Feldman, A neuroleptic malignantlike syndrome due to levodopa therapy withdrawal. JAMA, 1985. 254(19): p. 2792-5.
10. Gibb, W.R. and D.N. Griffith, Levodopa withdrawal syndrome identical to neuroleptic malignant syndrome. Postgrad Med J, 1986. 62(723): p. 59-60.
11. Keyser, D.L. and R.L. Rodnitzky, Neuroleptic malignant syndrome in Parkinson’s disease after withdrawal or alteration of dopaminergic therapy. Arch Intern Med, 1991. 151(4): p. 794-6.
12. Gordon, P.H. and S.J. Frucht, Neuroleptic malignant syndrome in advanced Parkinson’s disease. Mov Disord, 2001. 16(5): p. 960-2.
13. Newman, E.J., D.G. Grosset, and P.G. Kennedy, The parkinsonism-hyperpyrexia syndrome. Neurocrit Care, 2009. 10(1): p. 136-40.
14. Castillo, E., R.T. Rubin, and E. Holsboer-Trachsler, Clinical differentiation between lethal catatonia and neuroleptic malignant syndrome. Am J Psychiatry, 1989. 146(3): p. 324-8.
15. Fink, M., Neuroleptic malignant syndrome and catatonia: one entity or two? Biol Psychiatry, 1996. 39(1): p. 1-4.

To cite this abstract in AMA style:

D. Newbold, . . Down-titration of levodopa complicated by catatonia [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/down-titration-of-levodopa-complicated-by-catatonia/. Accessed October 5, 2025.
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