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

Levodopa is the major symptomatic therapy for PD and is the most common first-line therapy because it provides benefit to virtually all patients.^1,3 In the short-term, the effects of levodopa tend to be long-lasting and side effects are tolerable.¹ In the longer-term, 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’.

‘Wearing-off’ is a predictable recurrence of PD symptoms that precedes a scheduled dose of levodopa and usually improves with medication.⁴ By contrast, the less predictable fluctuations – sometimes called ‘yo‑yoing’ – are associated with more advanced stages of PD.⁵

References:
1.Obeso JA, Rodriguez-Oroz MC, Chana P. The evolution and origin of motor complications in Parkinson’s disease. Neurology 2000; 55 (11 Suppl 4): S13–S20.

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

3.Bloem BR, Okun MS, Klein C. Parkinson’s disease. Lancet 2021; 397 (10291): 2284–2303.

4.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.

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