Expert Review of Neurotherapeutics最新文献

Introduction: Calcitonin Gene-Related Peptide (CGRP)-targeted therapy has revolutionized migraine treatment since its first approval in 2018. CGRP-targeted therapy includes monoclonal antibodies (mAbs) and gepants, which modulate trigeminal nociceptive and inflammatory responses, alleviating pain sensitization involved in migraine pathogenesis. CGRP-targeted therapy is effective not only for migraine but also for other chronic headache disorders that share the CGRP pathway.

Areas covered: The authors review the latest developments and evidence for CGRP-targeted therapy for episodic migraine and chronic migraine. In addition, the authors discuss the emerging evidence on response prediction, menstrual migraine, vestibular migraine, idiopathic intracranial hypertension, post-traumatic headache, and the relationship between selected migraine comorbidities and CGRP.

Expert opinion: Since the launch of CGRP-targeted therapy, many practical issues have been raised. Generally, it's safe to combine CGRP-targeted mAbs and gepants; this is an excellent option for patients with partial response. When considering stopping CGRP-targeted therapy, although a disease-modifying effect is likely, the optimal time for discontinuation remains unknown. Finally, beyond migraine, CGRP-targeted therapy may be used for other chronic pain disorders and psychological comorbidities.

Introduction: Primary headaches, including migraines and cluster headaches, are highly prevalent disorders that significantly impact quality of life. Several factors suggest a key role for the hypothalamus, including neuroimaging studies, attack periodicity, and the presence of altered homeostatic regulation. The orexins are two neuropeptides synthesized almost exclusively in the lateral hypothalamus with widespread projections across the central nervous system. They are involved in an array of functions including homeostatic regulation and nociception, suggesting a potential role in primary headaches.

Areas covered: This review summarizes current knowledge of the neurobiology of orexins, their involvement in sleep-wake regulation, nociception, and functions relevant to the associated symptomology of headache disorders. Preclinical reports of the antinociceptive effects of orexin-A in preclinical models are discussed, as well as clinical evidence for the potential involvement of the orexinergic system in headache.

Expert opinion: Several lines of evidence support the targeted modulation of orexinergic signaling in primary headaches. Critically, orexins A and B, acting differentially via the orexin 1 and 2 receptors, respectively, demonstrate differential effects on trigeminal pain processing, indicating why dual-receptor antagonists failed to show clinical efficacy. The authors propose that orexin 1 receptor agonists or positive allosteric modulators should be the focus of future research.

Introduction: Gambling disorder (GD) is a mental health condition characterized by persistent and problematic betting behavior. GD generates distress and impairment, and treatment options include psychological and pharmacological interventions.

Areas covered: This narrative review explores existing pharmacological treatments for GD. The following classes of medications were considered: opioid-receptor antagonists (e.g. naltrexone and nalmefene), serotonin reuptake inhibitors (e.g. fluvoxamine, paroxetine, sertraline, escitalopram, and citalopram), glutamatergic agents (e.g. N-acetylcysteine (NAC), acamprosate, and memantine), mood stabilizers (e.g. topiramate, carbamazepine, lithium), and other medications (e.g. modafinil, nefazodone, olanzapine, haloperidol, tolcapone, and bupropion).

Expert opinion: Due to the limitations of the studies reviewed, solid conclusions regarding the optimal choice of pharmacotherapy for individuals with GD are challenging to draw at this time. Despite some medications, such as naltrexone and nalmefene, showing promising results, efficacy has varied across studies. The review highlights current gaps/limitations, including small sample sizes, limited diversity in participant demographics, the need for exploring different gambling subtypes and treatment responses, high placebo response rates, lack of longer-term longitudinal information, limited investigation of neurobiological correlates and co-occurring disorders, and the importance of implementation research. Further research is needed to address these gaps and explore additional medications, as well as interventions like neuromodulation.

Introduction: Borderline personality disorder (BPD) is a severe mental disorder characterized by emotion dysregulation, impulsivity, neuropsychological impairment, and interpersonal instability, presenting with multiple psychiatric comorbidities, functional disability and reduced life expectancy due suicidal behaviors.

Areas covered: In this perspective, the authors explore the application of noninvasive brain stimulation (NIBS) (rTMS, tDCS, and MST) in BPD individuals by considering a symptom-based approach, focusing on general BPD psychopathology, impulsivity and neuropsychological impairments, suicidality and depressive/anxious symptoms, and emotion dysregulation.

Expert opinion: According to a symptoms-based approach, NIBS interventions (particularly rTMS and tDCS) are promising treatment options for BPD individuals improving core symptoms such as emotional and behavioral dysregulation, neuropsychological impairments and depressive symptoms. However, the heterogeneity of stimulation protocols and of assessment tools used to detect these changes limits the possibility to provide definitive recommendations according to a symptom-based approach. To implement such armamentarium in clinical practice, future NIIBS studies should further consider a lifespan perspective due to clinical variability over time, the role of psychiatric comorbidities affecting BPD individuals and the need to combine NIBS with specialized psychotherapeutic approaches for BPD patients and with functional neuroimaging studies.

Introduction: The preventive effects of chronic physical exercise (CPE) on Alzheimer's disease (AD) are now admitted by the scientific community. Curative effects of CPE are more disputed, but they deserve to be investigated, since CPE is a natural non-pharmacological alternative for the treatment of AD.

Areas covered: In this perspective, the authors discuss the impact of CPE on AD based on an exhaustive literature search using the electronic databases PubMed, ScienceDirect and Google Scholar.

Expert opinion: Aerobic exercise alone is probably not the unique solution and needs to be complemented by other exercises (physical activities) to optimize the slowing down of AD. Anaerobic, muscle strength and power, balance/coordination and meditative exercises may also help to slow down the AD progression. However, the scientific evidence does not allow a precise description of the best training program for patients with AD. Influential environmental conditions (e.g. social relations, outdoor or indoor exercise) should also be studied to optimize training programs aimed at slowing down the AD progression.

Introduction: Alzheimer's disease (AD) is the predominant cause of dementia and a significant contributor to morbidity among the elderly. Patients diagnosed with AD face an increased risk of epileptic seizures.

Areas covered: Herein, the authors review the challenges in the diagnosis of seizures in patients with AD, the risks of seizures related to medications used in AD and the pharmacological treatment of seizures in AD. The authors also provide the reader with their expert opinion on the subject matter and future perspectives.

Expert opinion: Healthcare professionals should maintain a vigilant approach to suspecting seizures in AD patients. Acute symptomatic seizures triggered by metabolic disturbances, infections, toxins, or drug-related factors often have a low risk of recurrence. In such cases, addressing the underlying cause may suffice without initiating antiseizure medications (ASMs). However, unprovoked seizures in certain AD patients carry a higher risk of recurrence over time, warranting the use of ASMs. Although data is limited, both lamotrigine and levetiracetam appear to be reasonable choices for controlling seizures in elderly AD patients. Decisions should be informed by the best available evidence, the treating physician's clinical experience, and the patient's preferences.