Discussion
PD, dyskinesias, movement disorders
MOVEMENT DISORDERS
We have based this report on unpublished data collected from the TOLEDO trial and ‘real-world’ experience with apomorphine collected in a semi-structured way from movement disorders specialists. Patients were highly selected in the randomized clinical trial and monitored more closely than in clinical practice. The specifications of the TOLEDO protocol limited individual clinical decision making, for example, centers were not permitted to continue dose adjustments after the first four weeks of double-blind treatment. These differences were reflected in the questionnaire responses. Nevertheless, in both settings a stable apomorphine dose can be achieved in most patients within 3 weeks, and while the optimal hourly dose varies, it nearly always falls between 3 and 7 mg/hour.The protocols used in the TOLEDO study for starting treatment and reducing oral medication were fixed and standardized; in clinical practice, a greater variation occurs. The TOLEDO protocol, which resulted in clinically meaningful improvements in OFF periods and good tolerability, had been recommended by a panel of experts experienced with apomorphine, some of whom also participated in the questionnaire.Apomorphine infusion therapy should be individualized for each patient—including initiation, optimal dose, reduction in oral medications, and monitoring—and should focus on the patient’s treatment goals; dyskinesias in particular should prompt attempts to reduce oral medication as much as possible but gradually, and to increase the hourly apomorphine flow rate. Good communication greatly improves the likelihood of successful outcomes and patients should be encouraged to take control of the management of their pump, including inserting the needle under the skin of the abdominal wall.An advantage of apomorphine infusion therapy over other device-aided treatments is that it can be discontinued much more easily if results are unsatisfactory. In this regard, it is more appropriate to compare the withdrawal rates reported with apomorphine to those of oral dopamine agonists rather than to those reported from other device-aided therapies, such as gastro-jejunostomies.A retrospective study has suggested that the best candidates for apomorphine infusion are patients with a poor health-related quality of life and marked motor fluctuations (Meira et al. The apomorphine pump is much less expensive than enteral levodopa infusion or DBS, avoids the need for surgery and does not require a large team for long-term management. If patients need to move to residential care, apomorphine infusion can often be continued.In summary, apomorphine infusion is an effective, well-tolerated and minimally invasive device-aided treatment for PD patients with refractory levodopa response fluctuations that cannot be managed by adjuvant oral or transdermal medication and which can often be started without the need for hospital admission. To achieve the best outcomes, patients should be referred to specialist centers as soon as motor fluctuations become difficult to manage and apomorphine considered as a treatment option. Successful treatment requires commitment from patients and their families and continuing encouragement from their doctors and nurses, particularly in the early months of therapy.