Pimavanserin use in a movement disorders clinic: A single center experience

Objective: To assess clinical outcomes of Pimavanserin use in Parkinson disease associated psychosis (PDP). Background: Dopamine-receptor blockers (DRB) are used to treat PDP symptoms, though these may be associated with adverse effects, including worsening of Parkinsonism. There is a paucity of comparative studies with conventional neuroleptics. Pimavanserin, a selective 5-HT receptor inverse agonist, was FDA-approved in 2016 for treatment of PDP. Design/Methods: A retrospective chart review of patients prescribed pimavanserin was performed in August, 2017. Data on demographics, psychotic features, sleep, adverse effects was collected using a semi-structured telephone interview with patients and caregivers. Hallucination severity (HS) was quantified as mild (/week), moderate (1/week to \u3c1/day) or severe (daily/continuous). Results: 17 patients consented to participate in the study: 16 were diagnosed with PDP, 1 with Lewy body dementia. Mean duration of Parkinsonism was 11.8±8.0years, with 2.6±1.9 years of psychotic symptoms. At baseline, 93% reported severe hallucinations and 7%, moderate hallucinations. Three PDP patients discontinued pimavanserin by the time of interview (2 because of no benefit; 1 due to remission). 71.4% reported improvement of hallucination with pimavanserin. 6 patients received pimavanserin monotherapy: 33.3% reported no change in HS, 50% improved from severe to mild, and 16.6% improved from severe to moderate. 8 patients receiving pimavanserin and DRB: 2 reported no change in HS, 25% reported a change from severe to mild hallucinations, 37.5% reported decrease from severe to moderate hallucinations and 12.5% reported decrease from moderate to mild hallucinations. Five of 9 patients prescribed DRB (quetiapine and olanzapine) discontinued these medications with pimavanserin initiation. No major side effects were reported. One patient noted subjective improvement of sleep. Conclusions: Our survey, based on reallife experience shows that pimavanserin is well-tolerated and efficacious in treatment of PDP. It appears to be effective as both monotherapy and adjuvant treatment for moderate to severe psychosis for most patients

Pimavanserin use in a movement disorders clinic: a single-center experience

BACKGROUND: Parkinson\u27s disease psychosis (PDP) is a disabling non-motor symptom of Parkinson\u27s disease (PD) that is challenging to treat. Dopamine receptor blockers (DRB) are used to treat PDP, though these may be associated with adverse effects, including worsening of Parkinsonism. Pimavanserin, a selective 5-HT METHODS: A retrospective chart review of patients prescribed pimavanserin was performed in August, 2017. Data on demographics, psychotic features, sleep, and adverse effects was collected using a semi-structured telephone interview with patients or caregivers. Hallucination severity (HS) was quantified as mild (\u3c 1 episode/week), moderate (1/week to \u3c 1/day), or severe (daily/continuous). RESULTS: Seventeen patients consented to participate in the study; 16 were diagnosed with PDP, 1 with Lewy body dementia. Fourteen had co-morbid cognitive impairment/dementia. The mean duration of Parkinsonism was 11.8 ± 8.0 years, with 2.6 ± 1.9 years of psychosis. Eleven of the seventeen patients reported improvement of hallucinations of which 5/8 were initiated on pimavanserin monotherapy, and 6/9 reported improvement of HS with combination of DRB. Six of nine patients prescribed DRB were able to discontinue this medication after introduction of pimavanserin. Four patients discontinued medications (2, no benefit; 1, spontaneous resolution; 1, cost). No major side effects were reported, and two patients noted subjective improvement of sleep. CONCLUSION: In our series based on a small sample size, pimavanserin is well-tolerated and effective as both monotherapy and adjuvant treatment for moderate to severe. This medication can facilitate reduction or cessation of DRB medication

Longitudinal study of the substantia nigra in Parkinson disease: A high-field (1) H-MR spectroscopy imaging study

INTRODUCTION: The value of biomarkers in early diagnosis and development of therapeutics in Parkinson\u27s disease (PD) is well established. METHODS: We used proton magnetic resonance spectroscopy in a prospective, longitudinal study of 23 patients with early PD, naïve to dopaminergic therapy, and six age-matched healthy controls to examine the temporal changes in metabolic profile of substantia nigra over a period of 3 months. RESULTS: N-acetyl aspartate to creatine ratio at month 3 was compared with baseline values in the PD and control groups, as well as the side-to-side difference of the ratio at baseline. By month 3, n-acetyl aspartate to creatine ratio had decreased by 4.4% in patients with PD (P = 0.024), without a concomitant change in healthy controls. The side-to-side asymmetry was significantly higher in the PD group (16.7%) vs. healthy controls (1.6%, P = 0.0024). CONCLUSION: Estimation of change in the n-acetyl aspartate to creatine ratio appears to be a fast, quantifiable, and reliable marker of dopaminergic neuronal viability in PD

A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease

BACKGROUNDCreatine and minocycline were prioritized for testing in Phase II clinical trials based on a systematic evaluation of potentially disease modifying compounds for Parkinson disease (PD).OBJECTIVETo test whether creatine and minocycline alter the course of early PD relative to a predetermined futility threshold for progression of PD in a randomized, double-blind, Phase II futility clinical trial. Agents that do not perform better than the futility threshold are rejected as futile and are not considered for further study.METHODSParticipants had a diagnosis of PD within 5 years, but did not require medications for the management of symptoms. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to either the time when there was sufficient disability to warrant symptomatic therapy for PD or 12 months, whichever came first. Subjects were randomized 1:1:1 to receive creatine 10 g/day, minocycline 200 mg/day, or matching placebo. The futility threshold was set as a 30% reduction in UPDRS progression based on the placebo/tocopherol arm of the Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) trial. p values < or = 0.1 indicate futility.RESULTSTwo hundred subjects were randomized to the three groups. Neither creatine (p = 0.96) nor minocycline (p = 0.66) could be rejected as futile based on the DATATOP futility threshold. The rate of progression for the calibration placebo group fell outside the 95% CI for the DATATOP historical control. In a sensitivity analysis, based on the threshold derived from the calibration placebo group, again neither drug could be rejected as futile. Tolerability was 91% in the creatine group and 77% in the minocycline group. Common adverse events included upper respiratory symptoms (26%), joint pain (19%), and nausea (17%).CONCLUSIONSBoth creatine and minocycline should be considered for definitive Phase III trials to determine if they alter the long term progression of Parkinson disease (PD). Additional factors must be weighed before selecting agents for Phase III trials, including safety, tolerability, activity, cost, and availability of these two agents in comparison with other agents currently in development for PD

A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease

OBJECTIVETo determine if future studies of coenzyme Q(10) and GPI-1485 in Parkinson disease (PD) may be warranted.METHODSWe conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold.RESULTSThe primary outcome measure (change in total Unified Parkinson's Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed.CONCLUSIONSCoenzyme Q(10) and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies

Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial

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