Drug holiday and management of Parkinson disease

  title={Drug holiday and management of Parkinson disease},
  author={William J. Weiner and William C. Koller and Stuart J. Perlik and Paul A. Nausieda and Harold L. Klawans},
  pages={1257 - 1257}
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… 

Figures and Tables from this paper

Reappraisal of temporary levodopa withdrawal ("drug holiday") in Parkinson's disease.

It is indicated that a drug holiday carries some risk and does not improve the efficacy of levodopa therapy or prevent the problems that occur with long-term administration.

Levodopa “drug holiday” with amantadine infusions as a treatment of complications in Parkinson's disease

The levodopa “drug holidays” with amantadine infusion is a valuable option in the therapy of advanced stages of PD and demonstrates a significant improvement both in the motor condition and complication of therapy.

Chronic low‐dose levodopa therapy in Parkinson's disease

Low dosage of levodopa is a desirable alternative, but not the answer to therapeutic failure, and use is recommended until the patient has a functional and/or psychological handicap that cannot be satisfactorily controlled with less potent antiparkinsonian agents.

Drug holidays in management of Parkinson disease

Clearance of long-lasting interfering Ldopa metabolites could be an alternative hypothesis to the “receptor theory” of L-dopa holiday.

The effects of acute levodopa withdrawal on motor performance and dopaminergic receptor sensitivity in patients with Parkinson's disease.

The minimum therapeutic dose of subcutaneous apomorphine needed to produce a similar improvement in patients' mobility, before and after several days of drug withdrawal, did not differ, thus providing no clinical evidence for alterations in striatal dopamine receptor sensitivity after acute levodopa withdrawal.

Practical Guidelines for the Drug Treatment of Parkinson’s Disease

Although still at the stage of preliminary clinical investigation, catechol-O-methyl-transferase inhibitors appear to have promise for reducing the severity and incidence of levodopa-induced motor fluctuations.

Effect of duration of levodopa/decarboxylase inhibitor therapy on the pharmacokinetic handling of levodopa in elderly patients with idiopathic Parkinson's disease

The amount by, and time for which, the plasma levodopa concentration exceeds any critical threshold for the competitive active uptake process into the brain may decrease with duration of therapy, which may explain in part the limited reversal of the neurological deficit.

Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease

Although symptom duration was the best predictor of the severity of untreated parkinsonism, levodopa dose correlated best with response half‐time, and may provide a quantitative index of central mechanisms that favor the development of the wearing‐off and on‐off phemonena.

Initiation of levodopa therapy in parkinsonian patients should be delayed until the advanced stages of the disease.

  • E. Melamed
  • Medicine, Psychology
    Archives of neurology
  • 1986
It is uncertain whether levodopa should be given to all parkinsonian patients immediately on diagnosis and regardless of the stage and severity of the disorder or whether its long-term administration should be withheld and delayed in milder cases and restricted to those patients who are in the more advanced stages.

Magnetic fields in the treatment of Parkinson's disease.

Application of weak magnetic fields with a frequency of 2 Hz and intensity of 7.5 picotesla for a 6 minute period resulted in a rapid and dramatic attenuation of Parkinsonian disability and an almost complete resolution of the dyskinesias.



Early-morning dystonia. A late side effect of long-term levodopa therapy in Parkinson's disease.

  • E. Melamed
  • Medicine, Psychology
    Archives of neurology
  • 1979
Four women with Parkinson's disease undergoing prolonged levodopa therapy had daily episodes of dystonic posturing, affecting one lower extremity, several years after initiation of treatment, and early-morning dystonia may represent another late side effect secondary to long-term Levodopa administration in parkinsonism.

Enhanced response to low doses of levodopa after withdrawal from chronic treatment

Park insonian patients who respond to levodopa usually require weeks of therapy and graded increases of dose to levels of 2 to 4 gm. per day to show significant clinical benefit. ’ -4 They usually

Mental symptoms in Parkinson's disease during chronic treatment with levodopa

The results suggest that the high incidence of dementia in patients with Parkinson's disease who take levodopa reflects prolongation of the course of the illness rather than a direct effect of the medication.

Six years of high-level levodopa therapy in severely akinetic parkinsonian patients.

  • A. Barbeau
  • Medicine, Psychology
    Archives of neurology
  • 1976
Levodopa improved the quality of life in greater than 53% of patients, but failed to modify the progression of the disease or change the prognosis.


Significantly better results on L-dopa were achieved for hypokinesia, rigidity, speed of movements, dysarthria and amimia, as did tests for speed and co-ordination, and tests for the activities of daily living showed a much greater improvement in the L- dopa group.

Levodopa-induced psychosis: a kindling phenomenon.

The hypothesis that chronic dopaminergic agonism may, via such a kindling mechanism, play a role in the development of some types of psychoses is supported.

Attempted use of haloperidol in the treatment of L-dopa induced dyskinesias1

  • H. KlawansW. Weiner
  • Medicine, Psychology
    Journal of neurology, neurosurgery, and psychiatry
  • 1974
It is suggested that long term haloperidol does not effectively decrease l-dopa induced dyskinesias without worsening Parkinsonism.

The L‐dopa on‐off effect in parkinson disease: Treatment by transient drug withdrawal and dopamine receptor resensitization

A patient who had become unpredictably responsive to L‐dopa was investigated, and in order to study whether it was possible to “resensitize” a patients who had already presumbly been desensitized by previous L-dopa therapy.

Reversal of two manifestations of dopamine receptor supersensitivity by administration of L-dopa.

The use of deliberate receptor sensitivity manipulation may be useful as a treatment for conditions involving disturbances in receptor sensitivity such as tardive dyskinesia and insulin resistant diabetes.