Options for Continuous Dopaminergic Stimulation Therapy
In patients with advanced Parkinson’s disease (APD), worsening motor symptoms due to motor response complications and dyskinesia (exacerbated by erratic gastric emptying associated with peroral therapy) may be treated optimally by switching to continuous dopaminergic stimulation (CDS) therapy. There are three CDS therapy options widely available for the treatment of APD:
- levodopa/carbidopa intestinal gel (LCIG) infusion;
- subcutaneous apomorphine (APO) infusion; and
- deep brain stimulation (DBS; primarily of the subthalamic nucleus [STN]), which is not strictly a CDS treatment but has similar effects.
But how do we choose between these treatments for a given Parkinson’s disease (PD) patient? Currently, there are no large-scale, randomised, placebo-controlled trials directly comparing the three CDS treatment options. We must therefore rely on indirect comparisons and a growing body of clinical experience to judge the appropriateness of each CDS therapy for individual patients.
Factors to Aid Treatment Choice
Inclusion and Exclusion Criteria
We can use various criteria to decide whether a patient is appropriate for a given treatment, including age, cost, practicalities (e.g., feasibility of surgery or availability of a multidisciplinary care team), cognitive impairment or psychosis (see Figure 1). APO infusion is the ‘simplest’ treatment in terms of administration, but may be slightly less effective in treating motor complications than DBS or LCIG infusion. Furthermore, different CDS treatments appear to improve different non-motor symptoms (NMS). If there is a 24-hour clinical need, DBS may be the better choice and, in the long-term, may be cheaper than pump therapies. If the patient is aged >70 years, they may not be a good candidate for DBS given the risks of surgery. In addition, cognitive impairment or severe psychosis may preclude all CDS therapies, but especially DBS. Patients with impulse control disorder, hypersexuality or severe orthostatic hypotension may not be good candidates for APO infusion. Co-morbidities such as gastrointestinal problems may make percutaneous endoscopic gastrostomy (PEG) fitting for LCIG infusion problematic. Any other disease that has an effect on life expectancy may make the neurologist more reluctant to suggest surgery, given the added risk of unpleasant side effects that may lead to death or severe morbidity.
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