"ViewpointsWhen is a Holiday Not a Holiday?Withdrawal of levodopa in Parkinsonism may not be justified

In Parkinson's disease, the idea of a 'drug holiday' from levodopa has arisen because of the high incidenceof complications associated with long term use of this drug. Loss of efficacy , dyskinesias, variable response,hallucinations, personality changes, orthostat ic hypotension or myoclonus occur in more than 50~ .of longterm users. Lowering the dose of levodopa results in worseninq of the Parkinsonism and the addition of

anticholinergics is not enough to offset this, while the addition of a dopamine agonist may bring back thedrug-induced complications.

In theory, the effect of the holiday is to allow the brain to re-establish a level of supersensitivity todopamine (by increasing the number of dopamine receptors) which has gradually diminished with levodopatherapy. In practice, the patient must undergo a period of discomfort as the symptoms of Parkinsonism mayworsen to the extent where he or she cannot move, swallow or talk. There is also an increased risk ofdepression, aspiration, thrombophlebitis , pulmonary embolism and a newly reported syndrome of fever,tachypnoea, confusion, elevated serum creatine kinase level and possible death on withdrawal of levodopa.

There have been only 4 studies of drug withdrawal for ~ 5 days and these encompassed a total of only 62patients and used variable methodology . Success rates were difficult to compare but in the largest study 25%were still improved after one year.

Considering the necessity for admission to hospital for 3-6 weeks during the drug holiday, the risksinvolved and the fact that the benefits are seldom maintained, some investigators will not continue researchinto drug holidays from levodopa until new evidence of substantial benefit is shown.Friedman. JH : Archives 01Inlernal Medicine 145: 913·9 15 (May (985)

2 INPHARMAItJ 8 Jun 1985 0156-2703 /85/0608-0002/0$01 .00/0 © ADtS Press