Clinical Neuropharmacology最新文献

Objective: Evaluate the safety and efficacy of zavegepant (BHV-3500), a recently approved nasal spray containing a third-generation calcitonin gene-related peptide receptor antagonist, for treating acute migraine attacks.

Methods: A comprehensive search was conducted across various databases up to 06/26/2023 to identify relevant randomized clinical trials (RCTs) on zavegepant's efficacy and safety in treatment of acute migraine attacks. Primary outcome: freedom from pain at 2 hours postdose. Safety outcomes were evaluated based on adverse events (AEs), with zavegepant 10 mg and placebo groups compared for incidence of AEs.

Results: Two RCTs, involving 2061 participants (1014 receiving zavegepant and 1047 receiving placebo), were quantitatively analyzed. An additional trial was included for qualitative synthesis. Zavegepant 10 mg exhibited a significantly higher likelihood of achieving freedom from pain at 2 hours postdose compared with the placebo group (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.28 to 1.84). It also showed superior relief from the most bothersome symptoms at 2 hours postdose compared with placebo (RR 1.26, 95% CI 1.13 to 1.42). However, the zavegepant 10 mg group experienced a higher incidence of AEs compared with placebo (RR 1.78, 95% CI 1.5 to 2.12), with dysgeusia being the most reported AE (RR 4.18, 95% CI 3.05 to 5.72).

Conclusion: Zavegepant 10 mg is more effective than placebo in treating acute migraine attacks, providing compelling evidence of its efficacy in relieving migraine pain and most bothersome associated symptoms. Further trials are necessary to confirm its efficacy, tolerability, and safety in diverse clinic-based settings with varied patient populations.

Background: For hematology cancer patients, the process of dying is described as "troublesome." Qualitative studies have focused on views of healthcare professionals and caregiver stakeholders. To date, there have been no studies from the patient's perspective on facing death while in the last year of life.

Objective: The aim of this study was to develop an understanding of the hematology cancer patient's experience of the process of dying in the last year of life.

Methods: The study method was constructivist grounded theory using semistructured interviews, a constant comparison technique, and memoing to collection and analysis of data. The 21 participants were attending a UK cancer center, a cancer unit, or a hospice.

Results: This article describes 1 core category within the incurable hematology cancer illness trajectory through 4 subcategories: transitional phase, chronic phase, dying phase, and liminal phase.

Conclusion: This unique study illustrates that, although life can be prolonged, "facing death" still occurs upon hospitalization and relapse regularly over the illness trajectory.

Implications for practice: It is important that clinical practice acknowledges those participants in an incurable illness trajectory while living are focused on avoiding death rather than the ability to cure the disease. Services need to be responsive to the ambiguity of both living and dying by providing holistic management simultaneously, especially after critical episodes of care, to enhance the process of care in the last year of life, and assessment should incorporate the discussion of experiencing life-threatening events.

Objective: Teratoma is a type of germ cell tumor that derived from early embryonic stem cells and germ cell lines, which can lead to a rare complication known as paraneoplastic encephalitis syndrome. Delayed removal of teratoma allows for continuing antigen presentation, inducing affinity maturation of the antibody and the generation of long-lived plasma cells that infiltrate both bone marrow and brain, which makes the patient nonresponsive to later removal of teratoma and refractory to immunotherapy. We present this rare case to remind clinicians to be vigilant for the recognition and removal of teratoma during the treatment of autoimmune encephalitis.

Methods: We retrospectively reviewed the clinical record of this 12-year 5-month-old female patient diagnosed with anti- N -methyl- d -aspartate receptor (anti-NMDAR) autoimmune encephalitis; her ovarian teratoma was unidentified on admission. She did not respond to immunosuppressive therapy until the mature ovarian teratoma identified 45 days after admission and removed the following day, nearly 2 months after symptom onset. This patient experienced nearly complete resolution of symptoms within the subsequent 2 weeks. In addition, we conducted a literature review of the clinical presentations and treatment of anti-NMDAR autoimmune encephalitis associated with ovarian teratoma in the pediatric population.

Results: Our findings suggest that clinicians should be vigilant for the recognition and removal of teratoma during the treatment of autoimmune encephalitis.

Conclusion: Female pediatric patients with suspected anti-NMDAR encephalitis should be screened for ovarian tumors immediately and treated in a multidisciplinary setting including neurology and obstetrics and gynecology.

Background: A mindfulness-based stress reduction program combined with music therapy is one of the interventions designed to help patients cope with stress and depression.

Objective: The aim of this study was to examine the effects of an online mindfulness-based stress reduction program combined with music therapy on stress, depression, and psychological well-being in adult patients with cancer.

Methods: This study was a single-blinded, prospective, randomized-controlled experimental design. One hundred twenty cancer patients were recruited (60 each in the intervention and control groups). Patients in the intervention group received a 10-day mindfulness-based stress reduction program combined with music therapy. Stress was measured with the State Trait Anxiety Inventory-State, psychological well-being was measured with the Psychological Well-being Scale, and depression was measured with the Beck Depression Inventory at baseline and the end of the study.

Results: The intervention group showed significantly lower stress and depression scores than the control group in the total scores at 10 days ( P < .05). The intervention group had significantly higher scores in the psychological well-being ( P < .001) than the control group at 10 days. Intragroup comparison of the stress and depression scores showed that posttest score of the intervention group was significantly lower than its pretest score ( P < .05).

Conclusion: Mindfulness-based stress reduction program combined with music therapy reduced the levels of stress and depressive symptoms and improved psychological well-being in cancer patients.

Implications for practice: A nurse-led mindfulness-based stress reduction program combined with music therapy is an innovative and effective psychological intervention that may be integrated with regular patient care for adults receiving treatment of cancer.

Objective: Burning mouth syndrome (BMS) is an intractable chronic pain disorder characterized by a burning sensation without organic abnormalities in the oral mucosa. Amitriptyline may be effective for BMS or, conversely, may exacerbate pain. QTc is necessary for monitoring psychotropic adverse effects, but it is not known if it is a predictor of efficacy for BMS. We investigated the efficacy of amitriptyline in BMS and its effect on QTc.

Methods: Visual analog scale and electrocardiogram were examined before and 1 month after treatment in 51 consecutive patients diagnosed with BMS according to the International Classification of Headache Disorders, Third Edition (ICHD-3), criteria and treated with amitriptyline.

Results: There were 26 amitriptyline responders and 25 nonresponders, with no differences in age, sex, and amitriptyline dosage. Amitriptyline responders showed little change in QTc, whereas nonresponders showed a trend toward significantly shorter QTc. Changes in visual analog scale correlated statistically significantly with changes in QTc (Spearman rank correlation coefficient: 0384; P = 0.0054). The degree of pain tended to worsen with QTc shortening.

Conclusion: Amitriptyline provides analgesia in about half of BMS patients, but some BMS patients have worse pain with amitriptyline. Not only do changes in the QTc detect amitriptyline adverse effects with prolongation, but also, conversely, its shortening predicts amitriptyline ineffectiveness.

Objective: In this report, we discuss the case of a patient with minimally conscious state (MCS) whose clinical condition significantly improved after Zolpidem therapy. We aim to provide supportive evidence for inclusion of zolpidem trials in patients with MCS.

Methods: Our team used electronic medical records, direct patient care experiences, and literature review to obtain information for this case report.

Results: Twice daily zolpidem therapy led to significant clinical improvement in our patient with MCS. In addition, this improvement was maintained throughout an increasingly arduous medical course.

Conclusions: Minimally conscious state is a disorder with limited proven therapeutic options. Zolpidem administration has demonstrated immense benefit in a select population of patients, including ours. Given the potential for great improvement with limited downside, zolpidem trial presents an intriguing treatment option. Further clarification of prognostic features to stratify responders and nonresponders to therapy is needed.

Objective: Data on the pharmacological treatment of gambling disorder are limited. Silymarin (derived from milk thistle) has antioxidant properties. The goal of the current study was to determine the efficacy and tolerability of silymarin in adults with gambling disorder.

Methods: Forty-three individuals (18 [41.9%] women; mean age=49.61 [±13.1] years) with gambling disorder entered an 8-week, double-blind, placebo-controlled study. Dosing of silymarin ranged from 150 to 300 mg twice a day. The primary outcome measure was the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS). Secondary outcome measures comprised the Gambling Symptom Assessment Scale and measures of depression and anxiety. Outcomes were examined using mixed-effect models.

Results: Silymarin did not statistically differentiate from the placebo on any of the outcome measures of interest, in terms of treatment group×time interactions. There was a robust response in the placebo group (57% reduction on the PG-YBOCS), and on average there was a 56% reduction in YBOCS score for the milk thistle.

Conclusions: The findings of this study do not support the use of silymarin/milk thistle in the treatment of gambling disorder but highlight the large placebo response seen in gambling disorder. Treatment interventions for gambling disorder need to better understand and address the placebo response.

Trial registration: ClinicalTrials.gov identifier: NCT02337634.

Background: Treatment of soft tissue sarcoma frequently involves extensive surgery, loss of mobility, and complex rehabilitation programs. Poorer patient-reported outcomes are reported in comparison to those from patients with other cancer types. Understanding patient experience is therefore important to support patients and improve care.

Objective: The aim of this study was an in-depth exploration of patients' experience of being diagnosed with soft tissue sarcoma.

Methods: Semistructured interviews and focus groups were conducted with 68 patients with soft tissue sarcoma (59% female; aged 23-82 years). These were analyzed using adapted framework analysis.

Results: Two overarching themes explained the factors influencing patients' experiences: individual and social factors to manage the impact of soft tissue sarcoma; and context and processes of care. Access to professionals with sarcoma expertise and services in specialist hospitals had an impact on patients' well-being. Lack of access to specialist services and coordinated care were associated with worse experiences. These were influenced by age and support from family/friends/other patients and were crucial in patients' adaptation to living with and beyond a sarcoma diagnosis.

Conclusion: We describe factors that both negatively and positively influenced the experience of patients with soft tissue sarcoma. Access to specialist soft tissue sarcoma and rehabilitation services and support tailored to patients' age and disease trajectory are needed to improve these experiences.

Implication for practice: Nurses are important for helping patients manage the long-term effects and directing them to supportive care services. Rehabilitation services need to be available and easily accessible.

Objectives: Lasmiditan holds important potential in treating migraine, but its ideal dose remains elusive. This meta-analysis is conducted based on aggregate data and aims to compare the efficacy of lasmiditan 200 mg versus 100 mg for acute treatment of migraine attack.

Methods: PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases were systematically searched, and we included the randomized controlled trials comparing the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients. This meta-analysis was conducted using the random-effect model or fixed-effect model based on the heterogeneity. The primary outcome was pain free at 2 hours. Secondary outcomes included pain relief at 2 hours, pain free at 24 hours, most bothersome symptom free at 2 hours, and adverse events.

Results: Seven randomized controlled trials and 6515 patients were included in this meta-analysis. Compared with lasmiditan 100 mg for migraine patients, lasmiditan 200 mg was able to significantly improve pain free at 2 hours (odd ratio [OR], 1.28; 95% confidence interval [CI], 1.14-1.44; P < 0.0001) and pain free at 24 hours (OR, 1.35; 95% CI, 1.14-1.60; P = 0.0005), but showed no effect on pain relief at 2 hours (OR, 1.00; 95% CI, 0.90-1.12; P = 0.98) or most bothersome symptom free at 2 hours (OR, 0.93; 95% CI, 0.83-1.03; P = 0.17). Lasmiditan 200 mg was associated with the increase in adverse events compared with lasmiditan 100 mg (OR, 1.28; 95% CI, 1.15-1.43; P < 0.0001).

Conclusions: Lasmiditan 200 mg is more effective to improve pain free at 2 hours and 24 hours than lasmiditan 100 mg for the acute treatment of migraine patients.

Objective: Refractory status epilepticus (RSE) treated with anesthetic agents can be associated with complications including respiratory depression and hypotension. Ketamine is an emerging RSE treatment, but optimal dosing and timing are unknown. We studied provider attitudes and practices regarding the use of ketamine for RSE.

Methods: A literature review informed the creation of the survey, developed by professionals in epilepsy, pharmacy, and neurocritical care. The survey was distributed to members of the Critical Care EEG Monitoring and Research Consortium, Neurocritical Care Society, American Academy of Neurology Synapse community, American Epilepsy Society, and the Canadian League Against Epilepsy. Descriptive statistics were calculated.

Results: There were 109 respondents. First-line agents for RSE were midazolam (53%), propofol (42%), pentobarbital (2%), and ketamine (1%). Reasons for ketamine use included failure of midazolam/propofol to control seizures (81%) or hypotension on another anesthetic (35%). Perceived contraindications included hypertension (37%), elevated intracranial pressure (24%), and heart failure (18%). Perceived benefits included decreased use of vasopressors (53%) and more rapid RSE control when used adjunctively (49%). Routine ketamine users often treated more than 10 RSE cases per year, worked as intensivists or at academic institutions. Of the respondents, 59% found ketamine useful for RSE and 94% were interested in learning more about its use.

Conclusions: Although most participants found ketamine helpful for RSE, it is mainly used as a second-line agent adjunctively with midazolam or propofol. Perceived ketamine benefits included decreased need for hemodynamic support and more rapid seizure control when used in conjunction with other anesthetics. Perceived contraindications centered on cardiac and intracranial pressure concerns.