Apomorphine titration with and without anti-emetic pretreatment in patients with Parkinson's disease experiencing OFF episodes: A modified Delphi panel.

Introduction: In the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed.

Methods: This modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment.

Importance of time to ON versus wearing OFF in total daily OFF time experienced by patients with Parkinson's disease.

Most patients with Parkinson's disease (PD) receiving levodopa (LD)/DOPA decarboxylase inhibitors develop motor fluctuations with an increasing amount of OFF time, negatively impacting patient quality of life. Herein, we review the evidence supporting the substantial, yet underappreciated contribution of delays in time to ON (including delayed ON and no ON) to total daily OFF time. Most clinical studies use patient diaries that do not capture time to ON and wearing OFF separately as related to LD dosing, and consequently, most OFF time has generally been attributed to wearing OFF.

Clinical Use of On-Demand Therapies for Patients with Parkinson's Disease and OFF Periods.

On-demand therapies for Parkinson's disease (PD) provide rapid, reliable relief for patients experiencing OFF periods; however, practical guidelines on the use of these therapies are not generally available. This paper reviews the use of on-demand treatments. Motor fluctuations occur in nearly all patients with PD after long-term use of levodopa.

How to manage the initiation of apomorphine therapy without antiemetic pretreatment: A review of the literature.

Introduction: Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine.

Methods: To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD.

Tardive Dyskinesia in Older Persons Taking Antipsychotics.

Tardive dyskinesia (TD) is a hyperkinetic movement disorder caused by the use of dopamine receptor-blocking agents (DRBAs), a category of medications that includes first- and second-generation antipsychotics (APs) and agents such as metoclopramide that are used for the treatment of nausea and gastrointestinal dysmotility. While TD can affect people of all ages, older age is associated with increased risk of TD and also with the emergence of TD occurring after shorter treatment durations and lower dosages of DRBAs. TD is characterized by involuntary movements that include the face, limbs, and trunk, and is associated with increased comorbidities, social stigmatization, and impaired physical and mental health.

Effects of Gocovri (Amantadine) Extended-Release Capsules on Motor Aspects of Experiences of Daily Living in People with Parkinson's Disease and Dyskinesia.

Introduction: Gocovri, a bedtime-administered delayed-release/extended-release capsule formulation of amantadine, is the only drug approved by the US Food and Drug Administration as levodopa-adjunctive therapy for the treatment of OFF episodes and/or dyskinesia in Parkinson's disease (PD). Part II of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) assesses patient-perceived disability on experiences of daily living affected by PD motor symptoms. We analyzed Gocovri-related changes in MDS-UPDRS Part II ratings in two placebo-controlled clinical trials.

Capturing Initial Understanding and Impressions of Surgical Therapy for Parkinson's Disease.

Deep Brain Stimulation (DBS) is an underutilized surgical therapy for Parkinson's Disease (PD). Both physician and patient hesitancies have been described as potential barriers to DBS, but the specifics of patient perceptions of DBS have not been well-characterized in the general PD population. To characterize the understanding and impressions of surgical therapy in PD patients prior to formal surgical evaluation.

Early Recognition and Treatment of Tardive Dyskinesia in Patients With Mood Disorders and Schizophrenia.

​​​​Early Recognition and Treatment of Tardive Dyskinesia in Patients With Mood Disorders and Schizophrenia Click to enlarge page​​.

Treatment Strategies for Tardive Dyskinesia.

Tardive dyskinesia (TD), a condition of potentially irreversible abnormal involuntary movements that is associated with dopamine receptor blocking agents (DRBAs), produces significant impairment of functioning and quality of life for patients. Contrary to expectations, TD has not vanished despite the introduction of SGAs. Instead, changing prescription practices and increased off-label prescription of DRBAs have placed more patients than ever at risk of this potentially dangerous and disabling condition.

Earlier Diagnosis of Tardive Dyskinesia.

Because the symptoms of tardive dyskinesia (TD) have an insidious onset and fluctuating nature, and the risk of TD associated with second-generation antipsychotic (SGA) treatment has been underestimated, it has been challenging for clinicians to make an early and accurate TD diagnosis. More patients are at risk of developing this potentially permanent, disabling condition than ever before because of the widespread use of SGAs; therefore, prevention of TD, if possible, is of utmost importance. Clinicians must use reliable screening tools and diagnostic criteria to assess patients for TD, rule out other abnormal movement conditions, and make an accurate TD diagnosis.

Targeting neurons in the gastrointestinal tract to treat Parkinson's disease.

Background: Parkinson's disease (PD) is associated with α-synuclein (αS) aggregation within the enteric nervous system (ENS) and constipation. Squalamine displaces proteins that are electrostatically bound to intracellular membranes and through this mechanism suppresses aggregation of αS monomers into neurotoxic oligomers.

Objective: We sought to evaluate the safety of ENT-01 oral tablets (a synthetic squalamine salt), its pharmacokinetics, and its effect on bowel function in PD patients with constipation.

N-Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's Disease.

This study assessed the biological and clinical effects in patients with Parkinson's disease (PD) of N-acetyl-cysteine (NAC), the prodrug to l-cysteine, a precursor to the natural biological antioxidant glutathione. Forty-two patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for 3 months or standard of care only. Participants received prebrain and postbrain imaging with ioflupane (DaTscan) to measure dopamine transporter (DAT) binding.

Prevalence of Dyskinesia and OFF by 30-Minute Intervals Through the Day and Assessment of Daily Episodes of Dyskinesia and OFF: Novel Analyses of Diary Data from Gocovri Pivotal Trials.

Background: Parkinson's disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life.

Objective: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes.

Methods: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12.

Guidance for switching from off-label antipsychotics to pimavanserin for Parkinson's disease psychosis: an expert consensus.

Patients with Parkinson's disease psychosis (PDP) are often treated with an atypical antipsychotic, especially quetiapine or clozapine, but side effects, lack of sufficient efficacy, or both may motivate a switch to pimavanserin, the first medication approved for management of PDP. How best to implement a switch to pimavanserin has not been clear, as there are no controlled trials or case series in the literature to provide guidance. An abrupt switch may interrupt partially effective treatment or potentially trigger rebound effects from antipsychotic withdrawal, whereas cross-taper involves potential drug interactions.

The Emerging Role of Pimavanserin in the Management of Parkinson's Disease Psychosis.

Unlabelled: A panel of experts drawn from neurology, psychiatry, geropsychiatry, geriatrics, and pharmacy representatives of 3 health plans convened in New York City on July 30, 2016, with the objective of sharing opinions, ideas, and information regarding the optimal management of Parkinson's disease psychosis (PDP). Three key points emerged from the discussion: (1) Because of the nature of Parkinson's disease and PDP, finding appropriate treatment can prove challenging; (2) emerging therapies may present an opportunity for effective disease management; and (3) moving forward, provider and patient education regarding PDP and available treatment options is essential for well-managed symptoms and better quality of life. The panel reviewed current practices and formulated recommendations on moving forward in the treatment of PDP.

Clinical utility of DaTscan™ imaging in the evaluation of patients with parkinsonism: a US perspective.

Single photon emission computed tomography (SPECT) with Ioflupane I123 injection (DaTscan™) was approved by the Food and Drug Administration in 2011 for striatal dopamine transporter visualization to assist in the evaluation of adult patients with suspected parkinsonian syndromes. While brain SPECT imaging using DaTscan is a covered service under Medicare policy, there is a lack of consensus on its role in routine clinical practice in the US. Areas covered: To address this issue, an expert group of US-based movement disorders neurologists convened to discuss the clinical utility of DaTscan in movement disorders practices within the US.

N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data.

Backgound: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson's disease (PD).

Methods: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD.

An update on Parkinson's disease: improving patient outcomes.

Neurologists are faced with many challenges in caring for patients with Parkinson's disease (PD). This chronic, long-term illness that affects at least one million people in the United States requires a coordinated healthcare partnership between the physician and the patient. The importance of early diagnosis is essential to delaying disease progression and early diagnosis and intervention may be aided by recent advances in biomarkers, genomics, and imaging.