Expert Review of Neurotherapeutics最新文献

Introduction: Severe pediatric traumatic brain injury (spTBI), including abusive head trauma (AHT) in young children, is a major public health problem. Long-term consequences of spTBI include a large variety of physical, neurological, biological, cognitive, behavioral and social deficits and impairments.

Areas covered: The present narrative review summarizes studies and reviews published from January 2019 to February 2024 on spTBI. Significant papers published before 2019 were also included. The article gives coverage to the causes of spTBI, its epidemiology and fatality rates; disparities, inequalities, and socioeconomic factors; critical care; outcomes; and interventions.

Expert opinion: There are disparities between countries and according to socio-economic factors regarding causes, treatments and outcomes of spTBI. AHT has an overall poor outcome. Adherence to critical care guidelines is imperfect and the evidence-base of guidelines needs further investigations. Neuroimaging and biomarker predictors of outcomes is a rapidly evolving domain. Long-term cognitive, behavioral and psychosocial difficulties are the most prevalent and disabling. Their investigation should make a clear distinction between objective (clinical examination, cognitive tests, facts) and subjective measures (estimations using patient- and proxy-reported questionnaires), considering possible common source bias in reported difficulties. Family/caregiver-focused interventions, ecological approaches, and use of technology in delivery of interventions are recommended to improve long-term difficulties after spTBI.

Introduction: Agitation is a common and disruptive syndrome in dementia due to Alzheimer's disease (AD). Brexpiprazole was recently approved for this agitation of AD dementia and is the only therapy approved for this indication.

Areas covered: The authors review the chemistry, pharmacokinetics, mechanism of action, and pharmacodynamics of brexpiprazole. Phase 2/3 and Phase 3 studies of brexpiprazole for the treatment of agitation in dementia due to AD are described. These studies demonstrated efficacy and safety for the 2 mg/d and 3 mg/d doses. Agitation reduction from baseline was significantly greater in the active treatment groups compared to the participants on placebo as measured by the Cohen-Mansfield Agitation Inventory, the primary outcome. Treatment benefit was demonstrated on the Clinician Global Impression - Severity, the key secondary outcome. Safety and tolerability were comparable in drug and placebo arms of the studies.

Expert opinion: Approval by the Food and Drug Administration (FDA) of brexpiprazole for the treatment of agitation in dementia due to AD is an important milestone and regulatory precedent. This is the first approval for the treatment of any neuropsychiatric syndrome of AD. Brexpiprazole has a 'black box' warning for its use in psychosis caused by dementia due to an observed increase in mortality when using this class of antipsychotic agents in patients with dementia. Post-marketing surveillance will be key to understanding the safety profile of brexpiprazole. Brexpiprazole may be prioritized over the 'off label' use of other potential treatments for agitation.

Introduction: Vestibular migraine is a relatively common syndrome characterized by the occurrence of vertigo and other vestibular symptoms, frequently -but not always- accompanied by migraine symptoms, such as headache, photophobia, and phonophobia.

Areas covered: The authors review the acute or abortive treatment during an attack and prophylactic treatment of vestibular migraines, including pharmacological and non-pharmacological options.

Expert opinion: Since its recognition as an independent clinical entity is recent, studies concerning its different treatment alternatives are still scarce, and the level of evidence of published studies is generally low. For acute treatment, although available data are conflicting, triptans are usually tried first. Neurostimulating devices can also be considered for acute treatment of vestibular migraine. Regarding the preventive treatment of vestibular migraine, based on the results of two randomized clinical trials and its pharmacological properties, flunarizine should be considered as the first treatment option. Second-line preventive treatments encompass propranolol, topiramate, venlafaxine, and valproic acid. Among non-pharmacological options, vestibular rehabilitation seems to be a sound prophylactic treatment option.

Introduction: Migraine is a highly prevalent chronic, inherited neurological condition of the brain which carries a significant level of disability. Despite advances, there is an unmet need for more effective therapies.

Areas covered: Zavegepant nasal spray is a recent therapeutic option which acts as a calcitonin gene-related peptide receptor antagonist. The objective is to review the efficacy, safety, and additional results of the most recent trials investigating intranasal zavegepant for the acute treatment of migraine with or without aura. The authors searched PubMed using the keywords 'zavegepant,' 'Zavzpret,' 'migraine,' 'calcitonin gene-related peptide,' 'CGRP receptor antagonists.' This article covers Phase 1, Phase 2/3, and Phase 3 randomized, double-blind, placebo-controlled trials to evaluate the efficacy of intranasal zavegepant for treatment of acute migraine attacks.

Expert opinion: Intranasal zavegepant is an efficacious, safe, and tolerable anti-migraine drug based on clinical trials and clinical experience. It is especially useful for patients who experience attacks of sudden onset, those with nausea or vomiting, or a high cardiovascular risk burden. Dysgeusia was common; future studies are needed to better characterize this adverse event. Head-to-head studies are lacking with other migraine-specific therapies; the decision to treat should be patient-centered, with attack-specific characteristics in mind.

Introduction: Behavioral therapies are recommended as a first-line intervention for Tourette syndrome and persistent motor or phonic tic disorder.

Areas covered: In this review, the authors summarize randomized controlled trials on the comprehensive behavioral intervention for tics (CBIT), habit reversal therapy (HRT), and exposure and response prevention (ERP). Studies of face-to-face treatment, treatment by video conferencing, group treatment, and internet delivered treatment were assessed, as well as evidence of treatment predictors, modifiers, and mediators.

Expert opinion: There is high-quality evidence for face-to-face one-on-one treatment with CBIT, and data suggesting that one-on-one treatment by videoconference provides similar benefit. Limited data on group treatment with CBIT/HRT suggests inferiority to individual treatment, while internet-based CBIT programs appear more beneficial than wait list or psychoeducation. There is one face-to-face one-on-one treatment comparison of ERP to HRT, suggesting equal benefit. Internet-based ERP with minimal therapist support appears effective, although effect sizes are small. One study using behavioral therapy with ERP or HRT found similar benefit to medical treatment with antipsychotics. Data on predictors, modifiers, and mediators of treatment efficacy are emerging. In summary, behavioral therapies are an important treatment modality for tic disorders. Furthermore, important efforts to improve treatment accessibility are underway.