Unmasking levodopa resistance in Parkinson's disease

ABSTRACT Some motor and nonmotor features associated with Parkinson's disease (PD) do not seem to respond well to levodopa (or other forms of dopaminergic medication) or appear to become resistant to levodopa treatment with disease progression and longer disease duration. In this narrative revi...

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Published in:Movement disorders 2016-11, Vol.31 (11), p.1602-1609
Main Authors: Nonnekes, Jorik, Timmer, Monique H.M., de Vries, Nienke M., Rascol, Olivier, Helmich, Rick C., Bloem, Bastiaan R.
Format: Article
Language:English
Subjects:
Antiparkinson Agents - pharmacology
Cognitive ability
Disease resistance
Dopamine
Dopamine receptors
dopaminergic resistance
Drug Resistance
Gait
Humans
Levodopa
Levodopa - pharmacology
Motor task performance
Movement disorders
Neurodegenerative diseases
Parkinson Disease - drug therapy
Parkinson Disease - physiopathology
Parkinson's disease
Pharmacodynamics
Pharmacokinetics
Side effects
treatment
Tremor
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Summary:ABSTRACT Some motor and nonmotor features associated with Parkinson's disease (PD) do not seem to respond well to levodopa (or other forms of dopaminergic medication) or appear to become resistant to levodopa treatment with disease progression and longer disease duration. In this narrative review, we elaborate on this issue of levodopa resistance in PD. First, we discuss the possibility of pseudoresistance, which refers to dopamine‐sensitive symptoms or signs that falsely appear to be (or have become) resistant to levodopa, when in fact other mechanisms are at play, resulting in suboptimal dopaminergic efficacy. Examples include interindividual differences in pharmacodynamics and pharmacokinetics and underdosing because of dose‐limiting side effects or because of levodopa phobia. Moreover, pseudoresistance can emerge as not all features of PD respond adequately to the same dosage of levodopa. Second, we address that for several motor features (eg, freezing of gait or tremor) and several nonmotor features (eg, specific cognitive functions), the response to levodopa is fairly complex, with a combination of levodopa‐responsive, levodopa‐resistant, and even levodopa‐induced characteristics. A possible explanation relates to the mixed presence of underlying dopaminergic and nondopaminergic brain lesions. We suggest that clinicians take these possibilities into account before concluding that symptoms or signs of PD are totally levodopa resistant. © 2016 International Parkinson and Movement Disorder Society
ISSN:0885-3185
1531-8257
DOI:10.1002/mds.26712