Continuous subcutaneous apomorphine monotherapy in Parkinson’s disease

Abstract

Introduction and objective. Continuous subcutaneous apomorphine (APO) treatment is one of the 3 therapeutic options for advanced Parkinson's disease (PD), in addition to deep brain stimulation (DBS) and intrajejunal levodopa. Data from previously performed studies show that few PD patients can achieve APO infusion as monotherapy. The current pilot study presents the authors' experience in achieving APO monotherapy. Materials and method. During the last 2 years, 9 patients with APO were treated in the Department of Neurology of the Medical University of Lublin; each patient was offered a 5-day duration APO treatment as monotherapy. The main indication for the APO therapy was advanced PD with motor fluctuations and the patient's non-agreement for DBS therapy. Mean age of treated patients-65.11 years, mean disease duration-7.67 years, mean Hoehn-Yahr-2.67, mean L-dopa equivalent before APO treatment-1751.11 mg, mean daily dose of apomorphine as monotherapy-106.11 ± 14.09 mg. Results. All treated patients managed to achieve APO monotherapy. A statistically significant reduction was found in the duration of the 'off' states in the observed PD patients on APO monotherapy (p<0.05). No significant improvement was observed in the III motor score of the UPDRS on APO treatment, compared to optimized oral therapy used before APO treatment. Conclusions. APO monotherapy can be achieved in advanced PD, and seems to be a good therapeutic option for this group of patients, especially in that it allows a significant reduction in the off-time which significantly simplifies the drug regime. Nevertheless, hospital admission with experienced neurologist supervision is recommended when establishing a PD patient's APO monotherapy.

A Stage-Based Approach to Therapy in Parkinson’s Disease

“…Indeed, continuous subcutaneous Apomorphine (Apo) infusion seems to be a valid strategy to contrast refractory motor complications. Apo is a D1 and D2 receptor DA, whose subcutaneous delivery improves drug bioavailability and onset of action by avoidance of gastrointestinal transit time [165]. In an RCT, to date only published in abstract form, patients receiving Apo during their waking time at up to 8 mg/h experienced a reduction in off-time of 2.47 h compared to placebo after 12 weeks.…”

“…Different pathophysiological mechanisms may contribute to dyskinesia onset. As well as sensitization of dopamine receptors, also non-dopaminergic pathways, such as glutamatergic, serotoninergic and GABAergic, seem to be involved [165]. Since chronic stimulation of dopamine D1 receptors results in hyperactivation of NMDA glutamate receptors in the striatum [191], Amantadine, a nonselective NMDA antagonist, is considered useful as adjunct to l -dopa therapy for treating dyskinesias, despite its side effects which include confusion and visual hallucinations [15].…”

Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia—Literature Review

“…The efficacy of CSAI in controlling dyskinesias varies between studies. It is generally considered a likely option in patients with advanced PD [ 182 , 183 , 184 , 185 , 186 ] and has been described as a transitional option between the standard treatment and DBS, providing better control of dyskinesia [ 181 , 187 ]. However, it has sometimes been pointed out, that the increase in LEDD due to combined treatment with oral L-DOPA and CSAI led to a lack of initial improvement in dyskinesias and was a reason for discontinuing therapy [ 181 , 187 , 188 ].…”

“…However, it has sometimes been pointed out, that the increase in LEDD due to combined treatment with oral L-DOPA and CSAI led to a lack of initial improvement in dyskinesias and was a reason for discontinuing therapy [ 181 , 187 , 188 ]. In contrast, this problem was not observed with CSAI used in monotherapy, and the positive effect on dyskinesias was beneficial [ 185 ].…”

Peripheral Nerve Stimulation for the Treatment of Phantom Limb Pain: A Case Series

“…Central alterations with PNS include the activation of afferent non-nociceptive fbers which alter dorsal horn interneurons that are needed in the processing of nociceptive stimuli. PNS may also modulate wide dynamic range neurons in the dorsal horns [8] and can act peripherally by altering local micro-environments of nociceptive aferent fbers and reducing ectopic discharges [9]. PNS likely results in improvements in PLP by altering both the central and peripheral mechanism contributing to PLP.…”