End-of-dose akinesia

Certain fluctuations in clinical response to levodopa occur with increasing frequency as treatment continues. In some patients, these fluctuations relate to the timing of levodopa intake, and they are then referred to as wearing-off reactions or end-of-dose akinesia. In other instances, fluctuations in clinical state are unrelated to the timing of doses (on-off phenomenon). In the on-off phenomenon, off-periods of marked akinesia alternate over the course of a few hours with on-periods of improved mobility but often marked dyskinesia. The phenomenon is most likely to occur in patients who responded well to treatment initially. The exact mechanism is unknown. For patients with severe off-periods who are unresponsive to other measures, subcutaneously injected apomorphine may provide temporary benefit. 

Fluctuations in Response to Levodopa. Several distinct fluctuations in the response to levodopa are fairly common in most patients.67,69 80 End-of-dose akinesia describes the phenomenon where the effectiveness of the drug simply seems to wear off prior to the next dose. This condition, known also as wearing off, is usually resolved by adjusting the quantity and timing of levodopa administration (i.e., smaller doses may be given more frequently), or by using a sustained release form of the drug. 

End-of-dose akinesia A phenomenon in Parkinson disease in which the effectiveness of the medication wears off toward the end of the dosing interval, resulting in a virtual lack of volitional movement from the patient. 

---