CNS Drugs

Although the study of cognitive disengagement syndrome (CDS; previously called sluggish cognitive tempo) first emerged in the 1980s, very little is known about treating CDS or its impact on evidence-based interventions for attention-deficit/hyperactivity disorder (ADHD) with which it frequently co-occurs. The objective of this leading article was to investigate the existing evidence on medication treatment and CDS, including studies that have examined CDS response to medication and CDS as a moderator of ADHD treatment response...

The use of direct oral anticoagulants (DOACs) is increasing because of their superior efficacy and safety compared with vitamin K antagonists. Pharmacokinetic drug interactions, particularly those involving cytochrome P450- mediated metabolism and P-glycoprotein transport, significantly affect the efficacy and safety of DOACs. In this article, we assess the effects of cytochrome P450- and P-glycoprotein-inducing antiseizure medications on DOAC pharmacokinetics in comparison to rifampicin. Rifampicin decreases to a varying extent the plasma exposure (area under the concentration-time curve) and peak concentration of each DOAC, consistent with its specific absorption and elimination pathways...

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BACKGROUND: Nerve growth factor (NGF), the first-discovered member of the neurotrophin family, has long been regarded as a potential drug to combat acute and chronic neurodegenerative processes. However, the pharmacokinetic profile of NGF is poorly described. OBJECTIVES: The aim of this study was to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of a novel recombinant human NGF (rhNGF) in healthy Chinese subjects. METHOD: The study randomized 48 and 36 subjects to receive (i) single-ascending dose (SAD group; 7...

BACKGROUND: STRIVE was a prospective, 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative patients with early relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE: Study objectives examined the effects of natalizumab on cognitive processing speed, confirmed disability improvement (CDI), and patient-reported outcomes (PROs). METHODS: Clinical and PRO secondary endpoints were assessed annually over 4 years in STRIVE...

BACKGROUND AND OBJECTIVE: Ketamine may work as an anti-inflammatory agent, and it increases the levels of vascular endothelial growth factor (VEGF) in patients with treatment-resistant depression. However, whether genes related to pro-inflammatory and anti-inflammatory cytokines and VEGF may predict the treatment response to ketamine remains unknown.Therefore the aim of this study was to analyze whether specific genes related to inflammatory processes and VEGF were associated with treatment response to low-dose ketamine in patients with treatment-resistant depression...

Daridorexant (Quviviq™) is a useful option for the treatment of insomnia disorder, which has shown efficacy in younger and older adults. It antagonises the orexin receptors, thereby reducing the wake drive. Daridorexant is the first dual orexin receptor antagonist to be approved for the treatment of chronic insomnia in the EU and has been approved for insomnia in the USA. In phase 3 clinical trials, daridorexant dose-dependently improved objective latency to persistent sleep, objective wake time after sleep onset, subjective total sleep time and, at the 50 mg dose, subjective daytime functioning compared with placebo...

Rimegepant [Nurtec® ODT (USA); Vydura® (EU)] is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine with or without aura in adults, and for the preventive treatment of episodic migraine in adults. Rimegepant is available as an orally disintegrating tablet (ODT), which offers convenience and a potentially faster response time than the conventional tablet formulation. In pivotal phase III trials, rimegepant was more effective than placebo at relieving pain and the most bothersome symptom when taken as needed for the acute treatment of migraine...

BACKGROUND: Teriflunomide is a disease modifying treatment (DMT) approved for relapsing-remitting multiple sclerosis (RRMS) in adults and children. It reduces lymphocyte proliferation by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) and thereby the pyrimidine synthesis. Although most DMTs in multiple sclerosis (MS) modulate or inhibit the immune system in the periphery, the efficacy may improve if the agent also targets immune activity within the central nervous system (CNS), acts as a neuro-protective and enhances neuro-regeneration...

BACKGROUND AND OBJECTIVE: Cerebral venous thrombosis (CVT) is a rare disease, and data regarding direct oral anticoagulant therapy are insufficient. Apixaban could have a safer profile than other direct oral anticoagulants. We present our case series of patients with CVT treated with apixaban and a systematic review of published real-world cases. METHODS: We described our series of patients with CVT treated with apixaban and searched PubMed for similar published cases with reported complete outcome data: recanalisation rate, recurrent CVT, modified Rankin score, intracranial haemorrhage, other bleedings and mortality...

It has now been established that a perturbation in gut microbiome composition exists in multiple sclerosis (MS) and its interplay with the immune system and brain could potentially contribute to the development of the disease and influence its course. The effects of the gut microbiota on the disease may be mediated by direct interactions between bacteria and immune cells or through interactions of products of bacterial metabolism with immune and CNS cells. In this review article we summarize the ways in which the gut microbiome of people with MS differs from controls and how bacterial metabolites can potentially play a role in MS pathogenesis, and examine approaches to alter the composition of the gut microbiota potentially alleviating gut dysbiosis and impacting the course of MS...

Anorexia nervosa is a disorder associated with serious adverse health outcomes, for which there is currently considerable treatment ineffectiveness. Characterised by restrictive eating behaviours, distorted body image perceptions and excessive physical activity, there is growing recognition anorexia nervosa is associated with underlying dysfunction in excitatory and inhibitory neurometabolite metabolism and signalling. This narrative review critically explores the role of N-methyl-D-aspartate receptor-mediated excitatory and inhibitory neurometabolite dysfunction in anorexia nervosa and its associated biomarkers...

BACKGROUND: OnabotulinumtoxinA (BTX-A) and anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (anti-CGRP mAbs) are approved drugs for chronic migraine (CM), a difficult-to-treat condition. Optimization of CM patient management by choosing the best options and determining appropriate time for switching or adding concomitant treatments are highly needed. OBJECTIVE: Evaluate clinical response to anti-CGRP mAbs in patients who switched from BTX-A due to ineffectiveness defined by different cut-offs and assess the retention rate, effectiveness, and safety of both drugs within the first 9 months of treatment...

Multiple sclerosis (MS) is a chronic autoimmune demyelinating and neurodegenerative disease of the central nervous system with a wide variety of clinical phenotypes. In spite of the phenotypic classification of MS patients, current data provide evidence that diffuse neuroinflammation and neurodegeneration coexist in all MS forms, the latter gaining increasing clinical relevance in progressive phases. Given that the transition phase of relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS) is not well defined, and widely accepted criteria for SPMS are lacking, randomised controlled trials (RCTs) specifically designed for the transition phase have not been conducted...

BACKGROUND AND OBJECTIVES: Understanding the multi-faceted treatment outcomes of newly diagnosed epilepsy is critical for developing rational therapeutic strategies. A meta-analysis was conducted to derive pooled estimates of a range of seizure outcomes in children and adults with newly diagnosed epilepsy commenced on antiseizure medication treatment, and to identify factors associated with different outcomes. METHODS: PubMed/EMBASE were screened for eligible articles between 1 January, 1995 and 1 May, 2021 to include unselected cohort studies with a ≥ 12-month follow-up of seizure outcomes...

Attention-deficit/hyperactivity disorder (ADHD) is a common and impairing mental disorder. Individuals with ADHD typically experience symptoms from awakening throughout the entire day, contributing to impaired function at home, at school, and in the workplace. Treatment is available to address the symptoms of ADHD; however, the extent to which treatments afford improved function remains less clear. Impaired function in children and adolescents, particularly in the early morning where multiple tasks must be completed, from getting out of bed, and having breakfast to leaving for school on time, is common even among stimulant-treated children, and can increase stress upon caregivers and family members...

The orexin (hypocretin) system comprises two neuropeptides (orexin-A and orexin-B) and two G-protein coupled receptors (the orexin type 1 and the orexin type 2 receptor). The system regulates several biological functions including appetite, the sleep-wake cycle, the stress response, and motivation and reward processing. Dysfunction of the orexin system has been implicated in the pathophysiology of depression in human and animal studies, although the exact nature of this dysfunction remains unclear. Orexin receptor antagonists (ORAs) are a class of compounds developed for the treatment of insomnia and have demonstrated efficacy in this area...

Adaptation of the brain to the presence of a drug predicts withdrawal on cessation. The outcome of adaptation is often referred to as 'physical dependence' in pharmacology, as distinct from addiction, although these terms have unfortunately become conflated in some diagnostic guides. Physical dependence to antidepressants may occur in some patients, consistent with the fact that some patients experience withdrawal effects from these medications. It is thought that longer duration of use, higher dose and specific antidepressants affect the risk of antidepressant withdrawal effects as they might cause greater adaptation of the brain...

BACKGROUND: Long-acting injectable antipsychotics (LAIs) have been shown to improve adherence and prevent relapse in the treatment of schizophrenia and psychotic disorders, though longitudinal data on treatment outcomes are limited. OBJECTIVES: To establish the long-term acceptability and effectiveness of paliperidone palmitate once monthly (PP1M). METHODS: This independent 10-year mirror image study was carried out in a large urban mental health provider...

BACKGROUND AND OBJECTIVE: Daridorexant is a dual orexin receptor antagonist for the treatment of insomnia. In two phase III, 12-week studies in patients with insomnia disorder, daridorexant improved sleep and daytime functioning while maintaining a favorable safety profile. The objective of this 40-week extension study was to assess the long-term safety and tolerability of daridorexant. METHODS: Adults with insomnia disorder who completed the 12-week studies were invited to enroll in this double-blind extension study...