Expert Review of Neurotherapeutics最新文献

Introduction: Essential tremor (ET) and Parkinson's disease (PD) are the most common causes of tremor and the most prevalent movement disorders, with overlapping clinical features that can lead to diagnostic challenges, especially in the early stages.

Areas covered: In the present paper, the authors review the clinical and experimental studies and emphasized the major aspects to differentiate between ET and PD, with particular attention to cardinal phenomenological features of these two conditions. Ancillary and experimental techniques, including neurophysiology, neuroimaging, fluid biomarker evaluation, and innovative methods, are also discussed for their role in differential diagnosis between ET and PD. Special attention is given to investigations and tools applicable in the early stages of the diseases, when the differential diagnosis between the two conditions is more challenging. Furthermore, the authors discuss knowledge gaps and unsolved issues in the field.

Expert opinion: Distinguishing ET and PD is crucial for prognostic purposes and appropriate treatment. Additionally, accurate diagnosis is critical for optimizing clinical and experimental research on pathophysiology and innovative therapies. In a few years, integrated technologies could enable accurate, reliable diagnosis from early disease stages or prodromal stages in at-risk populations, but further research combining different techniques is needed.

Introduction: Obsessive-compulsive disorder (OCD) is a prevalent mental health issue characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions) that can cause significant life impairment. Despite cognitive-behavioral therapy (CBT) being the most effective treatment, some individuals experience insufficient symptom reduction or relapse.

Areas covered: This special report explores the potential of mindfulness-based interventions as complementary treatments for OCD, examining the specific techniques used and their practical application. In the initial section, the authors examine ten randomized control trial studies included in the meta-analysis conducted by Chien et al. (2022), demonstrating the effectiveness of mindfulness interventions. The authors focus on elucidating the specific mindfulness techniques used in these studies. Then, the authors discuss the integration of these mindfulness strategies into CBT, focusing on enhancing emotional regulation, cognitive flexibility, and acceptance of intrusive thoughts.

Expert opinion: While mindful based interventions (MBIs) show promise as adjunctive treatments for OCD, variability in OCD symptoms and treatment responses necessitate individualized therapeutic approaches. Further research is required to refine mindfulness-based techniques and optimize their effectiveness. Incorporating MBIs into standard CBT protocols may improve outcomes for patients with persistent OCD symptoms.

Introduction: Trigeminal neuralgia is a rare condition that can be effectively treated by carbamazepine or oxcarbazepine but these older drugs are associated with dose-dependent and potentially treatment-limiting adverse effects. Third-generation anticonvulsants, new calcitonin gene-related peptide blockers for migraine, and older drugs such as ketamine and cannabinoids may be promising adjuvants or monotherapeutic options.

Areas covered: The new drugs, their presumed mechanisms of action, safety and efficacy are discussed herein. There is a paucity of robust clinical evidence in support of these drugs for trigeminal neuralgia. New migraine agents are considered as well although migraines and trigeminal neuralgia are distinct, albeit similar, conditions. No new drugs have been released to market in recent years with the specific indication of trigeminal neuralgia.

Expert opinion: In real-world clinical practice, about half of trigeminal neuralgia patients take more than one agent for prevention and combination therapy may be the optimal approach. Combination therapy might allow for lower doses of carbamazepine or oxcarbazepine, thus reducing the number and severity of potential adverse events but the potential for pharmacokinetic drug-drug interactions must be considered. Drug therapy for trigeminal neuralgia involves acute or abortive treatments, often administered in hospital versus long-term preventive therapy, usually involving oral agents.

Introduction: Stimulants, including methylphenidate and amphetamines, are the first-line pharmacological treatment of ADHD in adults. However, in patients who do not respond or poorly tolerate stimulants, non-stimulant medications are usually recommended.

Areas covered: The authors provide a narrative review of the literature on non-stimulant treatments for adult ADHD, including controlled and observational clinical studies conducted on adult samples. Atomoxetine has been extensively studied and showed significant efficacy in treating adult ADHD. Issues related to dosing, treatment duration, safety, and use in the case of psychiatric comorbidity are summarized. Among other compounds indicated for ADHD in adults, antidepressants sharing at least a noradrenergic or dopaminergic component, including tricyclic compounds, bupropion, and viloxazine, have shown demonstratable efficacy. Evidence is also available for antihypertensives, particularly guanfacine, as well as memantine, metadoxine, and mood stabilizers, while negative findings have emerged for galantamine, antipsychotics, and cannabinoids.

Expert opinion: While according to clinical guidelines, atomoxetine may serve as the only second-line option in adults with ADHD, several other nonstimulant compounds may be effectively used in order to personalize treatment based on comorbid conditions and ADHD features. Nevertheless, further research is needed to identify and test more personalized treatment strategies for adults with ADHD.

Background: To identify the preferences and perceptions of migraine patients for acute and preventive treatment options and to investigate which treatment outcomes are the most important.

Design and methods: The authors performed a choice-format survey in a cohort of migraine patients from Greece and Cyprus. A self-administered questionnaire developed in collaboration with the Greek Society of Migraine Patients was used.

Results: Questionnaires were collected from 617 migraine patients. Efficacy was preferred over safety as the single most important parameter, both in acute and preventive treatment. When analyzing single outcomes, patients prioritized a complete pain remission at 1-hour post-dose for acute therapies. Regarding migraine prevention, a 75% reduction in frequency, intensity of pain, accompanying symptoms and acute medication intake were considered as most important. Conversely, outcomes routinely used in clinical trials, namely complete or partial pain remission at 2-hours post-dose for acute treatment and 50% or 30% reduction in migraine frequency for prevention, were not deemed particularly relevant. Tablet formulation was mostly preferred, both in acute and preventive treatment. Conclusion: Listening to patients' needs may add a piece of the puzzle that is generally missing in clinical practice and often explains the lack of adherence in both acute and preventative anti-migraine therapies.

Introduction: The onset of psychotic symptoms occurs prior to age 19 in 39% of the patients with schizophrenia. There are limited approved treatment options for adolescents with schizophrenia. Brexpiprazole was approved by the United States Food and Drug Administration (FDA) for treatment of schizophrenia in adolescents in 2022.

Areas covered: Extrapolation of adult data to youth and use of pharmacologic modeling coupled with open long-term safety data were used by the FDA to approve brexpiprazole for adolescent schizophrenia. They were all reviewed herein.

Expert opinion: D2 receptor partial agonist antipsychotic agents are preferred in the early phase of treatment of psychotic disorders. Approval of brexpiprazole in adolescent schizophrenia provides an additional option. Brexpiprazole was approved by the FDA on the basis of extrapolation of adult data without controlled trials in adolescents. This reduces placebo exposure in young people. Two previous agents (asenapine and ziprasidone) approved for adult schizophrenia failed to separate from placebo in adolescent schizophrenia studies; this partially undermines the process of extrapolation. For brexpiprazole, the paucity of data in adolescents relegates it to a second-line agent. More research on brexpiprazole is needed to delineate its relative role in the management of adolescent schizophrenia.

Introduction: The efficacy of trazodone for several psychopathologic dimensions of depression has been shown in the literature. Trazodone has been widely used in some clinical contexts (e.g. for insomnia and depression in the elderly). However, the role of trazodone in several aspects of depression is not well known.

Area covered: Eight experts from academic and medical centers across Italy met to identify the difficulties and barriers faced in daily clinical practice in the assessment and management of major depressive disorder and how the use of trazodone could address some unmet needs. The objective of the expert meetings and the present document was to increase knowledge of particular areas of treatment with trazodone.

Expert opinion: Evidence of the role of trazodone in patients affected by major depressive disorder with anxiety symptoms, insomnia, agitation, cognitive deficits, alcohol use disorders, physical comorbidities, and suicide risk has been identified, showing the effectiveness of trazodone in different presentations of major depressive disorder. The main characteristics of patients with depression for whom trazodone seems to be most effective have been identified, providing clinicians with information on possible uses of this drug in such population of patients.

Introduction: Despite its milder severity, the chronic nature of dysthymia leads to significant impairments and functional limitations. The treatment of dysthymia has received considerably less research attention compared to major depressive disorder (MDD).

Areas covered: The authors have conducted a comprehensive review on the treatment of dysthymia. Their primary objective was to identify therapeutic options that have demonstrated genuine efficacy. To do this, they searched the PubMed database, without any time restrictions, to retrieve original studies. The samples were exclusively comprised individuals diagnosed with dysthymia according to the diagnostic criteria outlined in DSM-III, DSM-III-R, DSM-IV, or DSM-IV-TR.

Expert opinion: Within the realm of dysthymia treatment, several antidepressants, including imipramine, sertraline, paroxetine, minaprine, moclobemide, and amineptine, in addition to the antipsychotic agent amisulpride, have demonstrated superiority over placebo. In certain studies, psychotherapeutic interventions did not distinguish themselves significantly from pharmacological treatments and failed to exhibit greater efficacy than a placebo. However, these findings remain inconclusive due to the limited number of studies and substantial methodological limitations prevalent in a significant proportion of them. Limitations include factors like small sample sizes, the absence of placebo comparisons, and a lack of study blinding.

Introduction: Non-traumatic spinal cord injury (NTSCI) is a term used to describe damage to the spinal cord from sources other than trauma. Neuroimaging techniques such as computerized tomography (CT) and magnetic resonance imaging (MRI) have improved our ability to diagnose and manage NTSCIs. Several practice guidelines utilize MRI in the diagnostic evaluation of traumatic and non-traumatic SCI to direct surgical intervention.

Areas covered: The authors review practices surrounding the imaging of various causes of NTSCI as well as recent advances and future directions for the use of novel imaging modalities in this realm. The authors also present discussions around the use of simple radiographs and advanced MRI modalities in clinical settings, and briefly highlight areas of active research that seek to advance our understanding and improve patient care.

Expert opinion: Although several obstacles must be overcome, it appears highly likely that novel quantitative imaging features and advancements in artificial intelligence (AI) as well as machine learning (ML) will revolutionize degenerative cervical myelopathy (DCM) care by providing earlier diagnosis, accurate localization, monitoring for deterioration and neurological recovery, outcome prediction, and standardized practice. Some intriguing findings in these areas have been published, including the identification of possible serum and cerebrospinal fluid biomarkers, which are currently in the early phases of translation.