December 2004
Deleu
D, Hanssens Y, Northway MG
Apomorphine, a short-acting dopamine D1 and D2
receptor agonist, was the first dopamine receptor agonist used to treat
Parkinson's disease. Subcutaneous apomorphine is currently used for the
management of sudden, unexpected and refractory levodopa-induced 'off'
states in fluctuating Parkinson's disease either as intermittent rescue
injections or continuous infusions. Other indications include the
challenge test for determining the dopaminergic responsiveness and
finding the appropriate dose of the drug in intermittent subcutaneous
administration.
Except for a rapid on- and offset of the
antiparkinsonian response with subcutaneous apomorphine, the magnitude
and pattern of the motor response to single dose of subcutaneously
administered apomorphine is qualitatively comparable to that of oral
levodopa. Seventy-five percent of patients achieve a clinically
significant improvement with a dose of apomorphine 4mg.
The efficacy of intermittent subcutaneous apomorphine
injections as an add-on to levodopa therapy in advanced Parkinson's
disease was explored in one short-term, randomised, double-blind,
placebo-controlled trial, one short-term and six long-term, open-label,
uncontrolled studies, including a total of 195 patients. These studies
provide evidence that this mode of administration was successful in
aborting 'off' periods and improving Parkinson's disease motor scores,
but tended to increase dyskinesias. No levodopa-sparing effect was
observed.
Eleven long-term, open-label, uncontrolled studies,
including a total of 233 patients evaluated the efficacy of continuous
subcutaneous apomorphine infusions in monotherapy or as an add-on to
levodopa therapy in advanced Parkinson's disease. These studies proved
that subcutaneous apomorphine infusions are successful in aborting 'off'
periods, reducing dyskinesias and improving Parkinson's disease motor
scores with the added benefit of a substantial levodopa-sparing effect.
The apomorphine challenge test has at least 80%
overall predictive ability to clinically diagnose Parkinson's disease
across the different stages of the disease and parkinsonian syndromes.
Similarly, those data also indicate that the apomorphine challenge test
has a >80% ability to predict dopaminergic responsiveness across all
stages of Parkinson's disease.
Adverse events are usually mild and consist
predominantly of cutaneous reactions and neuropsychiatric adverse
effects. The incidence of adverse effects is higher in patients
receiving continuous infusion than in those receiving intermittent
pulsatile administration.
Based on the results of these studies it is
recommended that subcutaneous apomorphine either as intermittent
injections or continuous infusions should be offered to any suitable
Parkinson's disease patient who has difficulties in his/her management
with conventional therapy. Low-dose levodopa therapy in combination with
waking-day hours subcutaneous apomorphine infusion would probably be
the most efficient treatment. Continuous subcutaneous apomorphine
infusions should be evaluated before more invasive measures or
neurosurgical interventions are contemplated.
