Drug holiday and management of Parkinson disease

Chronic treatment of parkinsonism with levodopa or levodopa/carbidopa is associated with problems that include dyskinesia, on-off phenomena, hallucinosis, and possible loss of therapeutic efficacy. We studied the effects of a period of transient drug withdrawal (drug holiday) in 16 patients who manifested these complications of chronic levodopa therapy. Patients were evaluated daily before, during, and after the period of drug withdrawal. Eleven of the 16 patients exhibited enhanced motor responsiveness after the holiday and required only half of the initial daily dose for improved motor performance. Most levodopa-induced side effects decreased after the holiday. Hallucinosis was ameliorated in all cases. The frequency of on-off phenomena and myoclonus also diminished. Sensitivity to levodopa-induced dyskinesia was not affected by the drug holiday. Because most patients required lower dosage after the holiday, dyskinesias were no longer present. These observations suggest that parkinsonian patients who suffer complications of chronic levodopa therapy may benefit from a period of drug withdrawal.