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

After years of treatment, levodopa therapy can be complicated by the development of motor complications, which include dyskinesias and motor fluctuations. The initial long duration response to a dose of levodopa (gold line on graph) becomes progressively shorter, and periods in which the patient responds to the drug become complicated by involuntary dyskinetic movements.

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