Drug holiday and management of Parkinson disease

Abstract

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.

Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease

“…Although consistent with the findings of a previous study [l 51, an explanation for this observation remains uncertain. Levodopa transport may be diminished in patients with on-off responses, especially across the gastrointestinal tract, and possibly also at the blood-brain barrier.…”

Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson's disease

“…It is evident clinically as a gradual improvement when levodopa is begun [8][9][10] and as a gradual worsening following cessation of therapy. 7,[10][11][12][13] The LDR is the largest component of symptomatic improvement during the first year of chronic levodopa therapy. 7 Nutt et al 7 found that after 1 year of treatment, a 72-hour withdrawal of levodopa was insufficient to allow resolution of symptomatic benefit, as patients had not returned to baseline.…”

Psychosis in Parkinson’s disease: ‘between a rock and a hard place’

“…The most commonly highlighted risk factors for psychosis appear to be increased age, greater duration of illness, and cognitive impairment (Parkinson's Study Group, 1999;McDowell et al, 1970;Sacks et al, 1970;Pederzoli et al, 1983;Glantz, 1986;Sanchez-Ramos et al, 1996;Weiner et al, 1980;Celesia & Barr, 1970;Cummings, 1988;Vieregge et al, 1996;Kippervasser et al, 1996). Much of this evidence is however anecdotal and there are relatively few methodologically sound studies.…”