What is a common issue with prolonged Carbidopa/Levodopa therapy?

• A. Wearing off
• B. Hyperreflexia
• C. Insomnia
• D. Weight gain

Answer: (A)

With long-term levodopa treatment, the benefit tends to wear off before the next dose. This wearing-off phenomenon happens because the brain’s dopamine system becomes more unstable as Parkinson disease progresses and the pulsatile dopaminergic stimulation from intermittent levodopa dosing fails to provide a consistent signal. As a result, motor symptoms such as slowness, stiffness, and tremor reappear toward the end of each dosing interval. Clinically, patients may also develop fluctuations and sometimes dyskinesias at peak dose, but the most commonly observed issue with prolonged therapy is this end-of-dose wearing-off. Management focuses on shortening dosing intervals, using controlled- or extended-release formulations, or adding other medications (like COMT inhibitors or MAO-B inhibitors) to smooth the dopaminergic stimulation and extend the duration of benefit.