An Open-Label, 8-Week Study of Safety and Efficacy of Pimavanserin Treatment in Adults with Parkinson's Disease and Depression.

BACKGROUND: Many patients with Parkinson's disease (PD) experience depression. OBJECTIVE: Evaluate pimavanserin treatment for depression in patients with PD. METHODS: Pimavanserin was administered as monotherapy or adjunctive therapy to a selective serotonin reuptake inhibitor or serotonin/noradrenaline reuptake inhibitor in this 8-week, single-arm, open-label phase 2 study (NCT03482882). The primary endpoint was change from baseline to week 8 in Hamilton Depression Scale-17-item version (HAMD-17) score. Safety, including collection of adverse events and the Mini-Mental State Examination (MMSE) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) scores, was assessed in patients who received ≥1 pimavanserin dose. RESULTS: Efficacy was evaluated in 45 patients (21 monotherapy, 24 adjunctive therapy). Mean (SE) baseline HAMD-17 was 19.2 (3.1). Change from baseline to week 8 (least squares [LS] mean [SE]) in the HAMD-17 was -10.8 (0.63) (95% CI, -12.0 to -9.5; p < 0.0001) with significant improvement seen at week 2 (p < 0.0001) and for both monotherapy (week 8, -11.2 [0.99]) and adjunctive therapy (week 8,-10.2 [0.78]). Most patients (60.0%) had ≥50% improvement at week 8, and 44.4% of patients reached remission (HAMD-17 score ≤7). Twenty-one of 47 patients experienced 42 treatment-emergent adverse events; the most common by system organ class were gastrointestinal (n = 7; 14.9%) and psychiatric (n = 7; 14.9%). No negative effects were observed on MMSE or MDS-UPDRS Part III. CONCLUSION: In this 8-week, single-arm, open-label study, pimavanserin as monotherapy or adjunctive therapy was well tolerated and associated with early and sustained improvement of depressive symptoms in patients with PD.

The past, present, and future of telemedicine for Parkinson's disease.

Travel distance, growing disability, and uneven distribution of doctors limit access to care for most Parkinson's disease (PD) patients worldwide. Telemedicine, the use of telecommunications technology to deliver care at a distance, can help overcome these barriers. In this report, we describe the past, present, and likely future applications of telemedicine to PD. Historically, telemedicine has relied on expensive equipment to connect single patients to a specialist in pilot programs in wealthy nations. As the cost of video conferencing has plummeted, these efforts have expanded in scale and scope, now reaching larger parts of the world and extending the focus from care to training of remote providers. Policy, especially limited reimbursement, currently hinders the growth and adoption of these new care models. As these policies change and technology advances and spreads, the following will likely develop: integrated care networks that connect patients to a wide range of providers; education programs that support patients and health care providers; and new research applications that include remote monitoring and remote visits. Together, these developments will enable more individuals with PD to connect to care, increase access to expertise for patients and providers, and allow more-extensive, less-expensive participation in research.

Are high doses of carbidopa a concern? A randomized, clinical trial in Parkinson's disease.

Recommended doses of carbidopa are 75-200 mg/day. Higher doses could inhibit brain aromatic amino-acid decarboxylase and reduce clinical effects. We compared 4-week outpatient treatments with carbidopa (75 and 450 mg/day) administered with L-dopa on the subjects' normal schedule. After each treatment phase, subjects had two 2-hour L-dopa infusions. The first infusion examined the effects of carbidopa doses administered the preceding 4 weeks, and the second infusion determined the acute effects of the two dosages of carbidopa. The antiparkinsonian effects and L-dopa and carbidopa plasma concentrations were monitored during the infusions. Twelve subjects completed the study. Carbidopa concentrations were eight times higher after the high-carbidopa phase. Area under the curve (AUC) for clinical ratings did not differ for the four L-dopa infusions, although AUC for plasma L-dopa was modestly increased with 450 mg of carbidopa. Nine subjects reported that the high-carbidopa outpatient phase was associated with greater response to L-dopa. Doses of 450 mg/day of carbidopa did not reduce the responses to L-dopa infusion, extending the safe range of carbidopa to 450 mg/day.