Clinical Management of Neuropsychiatric Symptoms of Huntington Disease: Expert-Based Consensus Guidelines on Agitation, Anxiety, Apathy, Psychosis and Sleep Disorders.

BACKGROUND: In clinical practice, several strategies and pharmacological options are available to treat neuropsychiatric symptoms of Huntington disease (HD). However, there is currently insufficient data for evidence-based guidelines on the management of these common symptoms. OBJECTIVE: We aimed to develop expert-based recommendations regarding the management of agitation, anxiety, apathy, psychosis, and sleep disorders. METHODS: Guideline development was based on a modified Institute of Medicine guideline process that accounted for a lack of evidence base. An international committee of 11 multidisciplinary experts proposed a series of statements regarding the description and management of each symptom. Statement assessment and validation was performed using a web-based survey tool and 84 international HD experts (neurologists and psychiatrists) who assessed the statements and indicated their level of agreement. RESULTS: High-level agreement (≥85% experts strongly agreed or agreed) was reached for 107 of the 110 statements that have been incorporated into the expert-based clinical recommendations presented herein. CONCLUSIONS: Clinical statements to guide the routine management of agitation, anxiety, apathy, psychosis, and sleep disorders in HD have been developed. Although not specifically tested in the HD population, clinical experience has shown that most of the neuropsychiatric symptoms discussed, when considered in isolation are treatable using pharmacologic and non-pharmacologic strategies developed for use in other populations. However, the management of neuropsychiatric symptoms in HD can be complex because neuropsychiatric symptoms often co-exist and treatment decisions should be adapted to cover all symptoms while limiting polypharmacy.

Contemporary health care for Huntington disease.

Providing medical care for people and families affected by Huntington disease (HD) can be a rewarding effort when realistic goals of improved quality of life and optimized functional status are set. Multiple disease symptoms can remit or improve with currently available pharmacologic and behavioral interventions, even though barriers exist that interfere with access to treatment. Connecting expert multidisciplinary teams with community-based care, developing treatment guidelines, and involving the HD family community in quality improvements can achieve an integrated system of health care delivery. Engaging people with HD in high-quality compassionate care will not only improve lives, it will also encourage participation in clinical trials that search for disease-modifying treatments that will reduce or bring the suffering of HD to an end.

Health Care Delivery Practices in Huntington's Disease Specialty Clinics: An International Survey.

BACKGROUND: Little is known about the organization of clinical services for Huntington's disease (HD). OBJECTIVE: To describe how health care services are organized and delivered in HD-clinics taking part in or eligible for the Enroll-HD study. METHODS: In 2014, a 69-item survey was administered to sites taking part in or eligible for the Enroll-HD study. RESULTS: Of 231 sites surveyed, 121 (52.2%) sites in Europe, North America, Latin America, and Oceania responded. Most sites in the sample serve large populations, with 61.1% serving more than 1.5 million people, and a further 33% serving >500,000. Almost all (86.0%) centers see patients from outside their region. The majority of centers (59.7%) follow 50-199 patients, 21.9% care for more than 200. Most centers provide care in all stages of HD, and nearly all review pre-symptomatic cases. Multidisciplinary case reviews are offered in 54.5% of sites, with outreach clinics offered by 48.1%. Videoconferencing and telemedicine are used by 23.6%. Separate consultations for caregivers are offered in more than half of the centers. Most centers (70.4%) report following published guidelines or local care pathways for HD. CONCLUSIONS: Most centers serve a large population and use a multidisciplinary approach. The survey gives insight into factors underpinning HD service delivery globally. There is a need for more in-depth studies of clinical practice to understand how services are organized and how such features may be associated with quality of care.

Assessment of cognitive symptoms in prodromal and early huntington disease.

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess cognitive symptoms in prHD and early HD individuals.

An International Survey-based Algorithm for the Pharmacologic Treatment of Irritability in Huntington's Disease.

It is generally believed that treatments are available to manage irritability in Huntington's disease (HD). However, lack of an evidence base prevents the establishment of treatment guidelines for this symptom. The research literature fails to address behavioral intervention strategies, drug selection, drug dosing, management of inadequate response to a single drug, or preferred drugs when additional behavioral symptoms comorbid to irritability are present. In an effort to inform clinical decision-making we surveyed an international group of experts to address these points. The experts consistently endorsed an antipsychotic drug (APD) as first choice for treatment of urgent and aggressive irritability behaviors. However, there was variation in practice patterns for treating less severe symptoms. Serotonin reuptake inhibitors (SSRIs) were first choice drug treatments by most respondents across all geographic regions. However, APDs were also endorsed as first choice for mild or moderate irritability, more frequently in Europe than in North America and Australia. Antiepileptic mood stabilizers (AEDs) were used by fewer respondents as first choice drug. Perceived efficacy for control of mild or moderate irritability was judged somewhat higher for APDs than SSRIs or AEDs. Benzodiazepines were not used as monotherapy, but frequently as an adjunctive drug in the setting of comorbid anxiety. Though many cited lack of experience with mirtazapine, others familiar with its use in HD chose it as an alternative monotherapy, or as adjunctive therapy if insomnia was a comorbid factor. This report presents survey results, reviews available irritability studies, and lastly proposes an algorithm for the treatment of irritability in HD derived from expert preferences obtained through this survey.

An International Survey-based Algorithm for the Pharmacologic Treatment of Obsessive-Compulsive Behaviors in Huntington's Disease.

It is generally believed that treatments are available to manage obsessive-compulsive behaviors (OCB's) in Huntington's disease (HD). However, lack of an evidence base prevents guideline development. The research literature fails to address the indications for behavioral interventions, drug selection, drug dosing, management of inadequate response to a single drug, and preferred drugs when additional behavioral symptoms comorbid to OCBs are present. In an effort to inform clinical decision-making, we surveyed an international group of experts to address these points. Survey results showed that experts utilized behavioral therapy only for patients with mild cognitive impairment. There was expert agreement that a selective serotonin reuptake inhibitor (SSRI) was the first choice drug, although clomipramine (CMI) was cited as a monotherapy choice by the smaller number of experts familiar with its use. Perceived efficacy for control of OCBs was similar for both SSRIs and CMI. Though less favored choices overall, antipsychotics (APDs) and antiepileptic mood stabilizers (AEDs) were most often used as augmentation strategies. In addition to survey results, this report reviews available studies, and lastly presents an algorithm for the treatment of OCBs in HD based on practice-based preferences obtained from this survey.

Advocacy Recruiting for Huntington's Disease Clinical Trials.

Recent clinical trials for Huntington's disease (HD) have been slowed by the inability to complete enrollment in a timely manner. We report a successful advocacy-based recruiting approach at Evergreen Neuroscience Institute, a new Huntington Study Group (HSG) investigative site that lacked an HD patient base. By partnering with community advocates and utilizing web-based advocacy group alerts, Evergreen ranked third of 27 North American sites conducting the Study of ACR16 for the Treatment of Huntington's disease (HART) for number of participants, and first for rate of recruitment -- all while decreasing the time and financial resources needed for site-based recruiting. To our knowledge this is the first published outcome study for advocacy recruiting in any disease population.

An International Survey-based Algorithm for the Pharmacologic Treatment of Chorea in Huntington's Disease.

It is generally believed that treatments are available to manage chorea in Huntington's disease (HD). However, lack of evidence prevents the establishment of treatment guidelines. The HD chorea research literature fails to address the indications for drug treatment, drug selection, drug dosing and side effect profiles, management of inadequate response to a single drug, and preferred drug when behavioral symptoms comorbid to chorea are present. Because there is lack of an evidence base to inform clinical decision-making, we surveyed an international group of experts to address these points. Survey results showed that patient stigma, physical injury, gait instability, work interference, and disturbed sleep were indications for a drug treatment trial. However, the experts did not agree on first choice of chorea drug, with the majority of experts in Europe favoring an antipsychotic drug (APD), and a near equal split in first choice between an APD and tetrabenazine (TBZ) among experts from North America and Australia. All experts chose an APD when comorbid psychotic or aggressive behaviors were present, or when active depression prevented the use of TBZ. However, there was agreement from all geographic regions that both APDs and TBZ were acceptable as monotherapy in other situations. Perceived efficacy and side effect profiles were similar for APDs and TBZ, except for depression as a significant side effect of TBZ. Experts used a combination of an APD and TBZ when treatment required both drugs for control of chorea and a concurrent comorbid symptom, or when severe chorea was inadequately controlled by either drug alone. The benzodiazepines (BZDs) were judged ineffective as monotherapy but useful as adjunctive therapy, particularly when chorea was exacerbated by anxiety. There was broad disagreement about the use of amantadine for chorea. Experts who had used amantadine described its benefit as small and transient. In addition to survey results, this report reviews available chorea studies, and lastly presents an algorithm for the treatment of chorea in HD which is based on expert preferences obtained through this international survey.