Change in levodopa response over time – ‘wearing-off’

Levodopa is the major symptomatic therapy for PD and provides benefit to virtually all patients.¹ During the early stage, the effects of levodopa tend to be long-lasting, and motor complications usually take a long time to develop.¹ Beyond this early stage, however, patients may struggle to maintain good symptom control as the duration of response to levodopa therapy becomes progressively shorter.¹ This problem is known as ‘wearing-off’.⁶

‘Wearing-off’ is a predictable recurrence of PD symptoms that precedes a scheduled dose of levodopa and usually improves with medication.⁶ By contrast, the less predictable fluctuations – sometimes called ‘yo‑yoing’ – are associated with more advanced stages of PD.⁷

However, it has been argued that there is no reason to delay the initiation of levodopa therapy in patients with PD, because the onset of motor fluctuations and dyskinesias are associated with the duration of the disease, rather than exposure to levodopa.³

References:
1. Obeso JA, Rodriguez-Oroz MC, Chana P. The evolution and origin of motor complications in Parkinson’s disease. Neurology 2000; 55 (Suppl 4): S13–S20.

2. Schapira AHV, Emre M, Jenner P, Poewe W. Levodopa in the treatment of Parkinson’s disease. Eur J Neurol 2009; 16 (9): 982–989.

3. Cilia R, Akpalu A, Sarfo FS, et al. The modern pre-levodopa era of Parkinson’s disease: insights into motor complications from sub-Saharan Africa. Brain 2014; 137 (Pt 10): 2731–2742.

4. Olanow CW, Stocchi F. Levodopa: A new look at an old friend. Mov Disord 2018; 33 (6): 859–866.

5. Cenci MA, Riggare S, Pahwa R et al. Dyskinesia matters. Mov Disord 2020; 35 (3): 392–396.

6. Bhidayasiri R, Hattori N, Jeon B, et al. Asian perspectives on the recognition and management of levodopa ‘wearing-off’ in Parkinson’s disease. Expert Rev Neurother 2015; 15 (11): 1285–1297.

7. Thanvi BR, Lo TCN. Long term motor complications of levodopa: clinical features, mechanisms, and management strategies. Postgrad Med J 2004; 80 (946): 452–458.