Apomorphine monotherapy in the treatment of refractory motor complications of Parkinson's disease: Long‐term follow‐up study of 64 patients

Abstract

Continuous subcutaneous infusion of apomorphine is now increasingly recognized as an effective treatment for refractory off periods and peak-dose dyskinesias in Parkinson's disease. We have reviewed our experience with apomorphine infusions, after a strategy decision in 1995 based on emerging preclinical data, to treat all patients with steady-state plasma levels of apomorphine throughout the waking day, minimizing additional pulsatile stimulation either by oral dopaminergic medication or bolus parenteral injections of apomorphine. Sixty-four patients have been treated with apomorphine pumps and 45 of these successfully converted to monotherapy, managing to discontinue all other forms of dopaminergic stimulation during the daytime treatment period with apomorphine. Patients were followed up for a mean of 33.8 months (range, 4-108 months) and clinical data analyzed retrospectively. The mean maintenance dose of apomorphine was 98 mg per 24 hours (monotherapy group: 103 mg/24 hours; polytherapy group: 93 mg/24 hours), which did not significantly increase at final follow-up. There was a mean maximum dyskinesia reduction of 64% (S.D. = 20) in the monotherapy group, compared to 30% (S.D. = 33) in those continuing on polytherapy (P < 0.001), despite a maintained increase in on time (monotherapy group: 55%, P < 0.005; polytherapy group: 50%, P = 0.05). Fifteen patients failed to successfully convert to monotherapy but benefited nonetheless, and only 3 failed apomorphine infusional therapy altogether. Reasons for failure were mixed, including difficulty with compliance and adverse effects such as daytime somnolence, skin complications, and painful dystonias. There was a significantly higher success rate in patients able to manage the treatment either independently or with the help of their caregiver. These results confirm that subcutaneous apomorphine monotherapy can reset peak-dose dyskinesia threshold in levodopa-treated patients and further reduce off-period disability after all available forms of oral medication, including long-acting dopamine agonists, have been tried.

Parkinson's disease, visual hallucinations and apomorphine: A review of the available evidence

“…The rich expression of D1-like receptors in the prefrontal cortex suggests a key role in top-down processes related to attention, a feature supported by a number of animal studies [74,75]. Absence of selective D1 agonists and antagonists has complicated study of these specific receptors in humans.…”

“…This piperidine moiety is also incorporated in the chemical structure of many antipsychotic medications, including piperidine phenothiazines, haloperidol, risperdone, bulbocapnine and other aporphines [75,76]. Based on the structural similarities, it has been argued that the antipsychotic potential of apomorphine is due to the specific action of this piperidine moiety in binding to dopaminergic and serotonergic receptors (particularly 5-HT2A-receptors), producing an antagonistic effect [9,12,[76][77][78].…”

Long-term Efficacy and Safety with Continuous Dopaminergic Stimulation Pump Treatments in Parkinson’s Disease

“…33,34 Oral levodopa dosage may often be substantially reduced, and monotherapy with APO is possible in some cases. 25 Monotherapy was as effective as polytherapy regarding reduction in 'off' time, but more effective in decreasing dyskinesias. 25 A possible reason for this finding is that high peak concentrations of levodopa are avoided or that sensitisation is partly reversed with continuous drug delivery.…”

“…[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] The general finding is that APO provides more time in motor states near normal performance and less time in 'off' and dyskinetic states as compared to conventional optimised therapy. Improvement in quality of life (QoL) may accompany the increased 'on' time, but so far publications on this aspect of APO infusion are sparse.…”

Algorithms for the treatment of motor problems in Parkinson's disease

“…Long‐term data are sparse, and it appears that the dropout rate is often higher than for the other advanced therapies 68. However, also this method is safe and effective in patients with bothersome motor complications,69, 70, 71 reducing off‐time and improving dyskinesias. Skin complications at the infusion site are among the most common adverse reactions, as are dopamine agonist side effects like neuropsychiatric changes, somnolence and orthostatic hypotension.…”