The initiation of antiparkinsonian treatment in early Parkinson’s disease (PD) is followed by a phase of good to excellent symptomatic response in nearly all patients; this has been referred to as the ‘honeymoon phase’. A stable response may be sustained in some patients throughout the course of their illness, but the majority will go on to develop motor complications, which include fluctuations and dyskinesias or involuntary movements.

In early PD, the clinical effect following an individual levodopa (L-dopa) dose wanes slowly and may still be detectable after days to weeks. As the disease progresses, the duration of effect gradually becomes shorter and patients become aware of a missed or delayed dose as their parkinsonian symptoms and signs re-emerge (‘wearingoff’). Eventually, the clinical response closely reflects peripheral L-dopa pharmacokinetics, characterised by a plasma half-life of 1–1.5 hours. More complex forms of on/off fluctuations may emerge, such as unpredictable fluctuations, delaye on or dose failures. All of these changes in motor functioning may cause considerable distress. However, off periods may be associated with non-motor symptoms, such as acute depression, dysphoria or pain, which may be even more disabling than the worsening of motor function.

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