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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 1 - 200 of 253 Journals sorted by number of followers
Nature Reviews Drug Discovery     Full-text available via subscription   (Followers: 333)
International Journal of Drug Policy     Hybrid Journal   (Followers: 249)
Journal of Clinical Oncology     Hybrid Journal   (Followers: 246)
Journal of Medicinal Chemistry     Hybrid Journal   (Followers: 160)
Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 159)
Drugs     Full-text available via subscription   (Followers: 143)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 98)
Pharmaceutical Research     Hybrid Journal   (Followers: 94)
European Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 87)
Drug Safety     Full-text available via subscription   (Followers: 84)
Annals of Pharmacotherapy     Hybrid Journal   (Followers: 56)
Biomaterials     Hybrid Journal   (Followers: 54)
Clinical Pharmacology & Therapeutics     Hybrid Journal   (Followers: 45)
Regulatory Toxicology and Pharmacology     Hybrid Journal   (Followers: 42)
Journal of Controlled Release     Hybrid Journal   (Followers: 38)
Annual Review of Pharmacology and Toxicology     Full-text available via subscription   (Followers: 38)
International Journal of Pharmaceutics     Hybrid Journal   (Followers: 37)
European Journal of Pharmaceutics and Biopharmaceutics     Hybrid Journal   (Followers: 35)
Clinical Therapeutics     Hybrid Journal   (Followers: 34)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 33)
British Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 32)
Drug Development and Industrial Pharmacy     Hybrid Journal   (Followers: 30)
AAPS Journal     Hybrid Journal   (Followers: 28)
Clinical Pharmacokinetics     Full-text available via subscription   (Followers: 27)
PharmacoEconomics     Full-text available via subscription   (Followers: 26)
Journal of Pharmacy and Pharmacology     Full-text available via subscription   (Followers: 26)
Critical Reviews in Toxicology     Hybrid Journal   (Followers: 25)
Toxicology and Applied Pharmacology     Hybrid Journal   (Followers: 24)
Journal of Clinical Psychopharmacology     Hybrid Journal   (Followers: 24)
International Journal of Pharmacy Practice     Full-text available via subscription   (Followers: 24)
Journal of Pain & Palliative Care Pharmacotherapy     Hybrid Journal   (Followers: 23)
Chemical Research in Toxicology     Hybrid Journal   (Followers: 22)
Journal of Pharmacokinetics and Pharmacodynamics     Hybrid Journal   (Followers: 22)
Trends in Pharmacological Sciences     Full-text available via subscription   (Followers: 20)
American Journal of Cardiovascular Drugs     Hybrid Journal   (Followers: 20)
Journal of Applied Toxicology     Hybrid Journal   (Followers: 19)
Pharmaceutical Development and Technology     Hybrid Journal   (Followers: 19)
Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 19)
Clinical Trials     Hybrid Journal   (Followers: 18)
Toxicology     Hybrid Journal   (Followers: 18)
Journal of Pharmaceutical and Biomedical Analysis     Hybrid Journal   (Followers: 18)
Clinical Toxicology     Hybrid Journal   (Followers: 18)
International Journal of Toxicology     Hybrid Journal   (Followers: 17)
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 16)
Journal of Clinical Pharmacy and Therapeutics     Hybrid Journal   (Followers: 16)
Journal of Natural Products     Hybrid Journal   (Followers: 16)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 15)
Toxicology Letters     Hybrid Journal   (Followers: 15)
Journal of Pharmacy Practice     Hybrid Journal   (Followers: 15)
Psychopharmacology     Hybrid Journal   (Followers: 15)
European Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 14)
Cardiovascular Drugs and Therapy     Hybrid Journal   (Followers: 14)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 14)
Drug and Chemical Toxicology     Hybrid Journal   (Followers: 13)
Journal of the American Pharmacists Association     Full-text available via subscription   (Followers: 13)
Current Medicinal Chemistry     Hybrid Journal   (Followers: 13)
American Journal of Therapeutics     Hybrid Journal   (Followers: 13)
Journal of Oncology Pharmacy Practice     Hybrid Journal   (Followers: 13)
Drug Discovery Today: Technologies     Full-text available via subscription   (Followers: 12)
Current Pharmaceutical Design     Hybrid Journal   (Followers: 12)
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 11)
Drug Development Research     Hybrid Journal   (Followers: 11)
Drug Metabolism and Disposition     Hybrid Journal   (Followers: 11)
Journal of Psychopharmacology     Hybrid Journal   (Followers: 11)
Toxicology in Vitro     Hybrid Journal   (Followers: 11)
Journal of Separation Science     Hybrid Journal   (Followers: 10)
Seminars in Oncology Nursing     Full-text available via subscription   (Followers: 10)
CNS Drugs     Full-text available via subscription   (Followers: 10)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Drugs & Aging     Full-text available via subscription   (Followers: 10)
Current Pharmaceutical Biotechnology     Hybrid Journal   (Followers: 10)
Food Additives & Contaminants Part A     Hybrid Journal   (Followers: 9)
Clinical Research and Regulatory Affairs     Hybrid Journal   (Followers: 9)
Journal of Pharmacology and Experimental Therapeutics     Hybrid Journal   (Followers: 9)
Journal of Medical Marketing     Hybrid Journal   (Followers: 9)
Biometrical Journal     Hybrid Journal   (Followers: 9)
Environmental Toxicology and Pharmacology     Hybrid Journal   (Followers: 9)
European Neuropsychopharmacology     Hybrid Journal   (Followers: 9)
Medicinal Chemistry     Hybrid Journal   (Followers: 9)
Prescriber     Hybrid Journal   (Followers: 9)
Drugs & Therapy Perspectives     Full-text available via subscription   (Followers: 9)
ChemMedChem     Hybrid Journal   (Followers: 9)
Current Opinion in Pharmacology     Hybrid Journal   (Followers: 9)
Inhalation Toxicology     Hybrid Journal   (Followers: 8)
Antiviral Research     Hybrid Journal   (Followers: 8)
Drug Metabolism Reviews     Hybrid Journal   (Followers: 8)
Progress in Neuro-Psychopharmacology and Biological Psychiatry     Hybrid Journal   (Followers: 8)
Human & Experimental Toxicology     Hybrid Journal   (Followers: 8)
BioDrugs     Full-text available via subscription   (Followers: 8)
Drug Delivery     Open Access   (Followers: 8)
Expert Review of Pharmacoeconomics & Outcomes Research     Full-text available via subscription   (Followers: 8)
European Journal of Pharmacology     Hybrid Journal   (Followers: 8)
Journal of Veterinary Pharmacology and Therapeutics     Hybrid Journal   (Followers: 7)
Experimental and Clinical Psychopharmacology     Full-text available via subscription   (Followers: 7)
Frontiers in Drug Design & Discovery     Hybrid Journal   (Followers: 7)
Clinical and Experimental Pharmacology and Physiology     Hybrid Journal   (Followers: 7)
Journal of Pharmacological and Toxicological Methods     Hybrid Journal   (Followers: 7)
Epilepsy Research     Hybrid Journal   (Followers: 7)
Clinical Drug Investigation     Full-text available via subscription   (Followers: 7)
Toxicology Mechanisms and Methods     Hybrid Journal   (Followers: 7)
Scandinavian Journal of Clinical and Laboratory Investigation     Hybrid Journal   (Followers: 7)
Journal of Cardiovascular Pharmacology     Hybrid Journal   (Followers: 7)
Toxicology and Industrial Health     Hybrid Journal   (Followers: 6)
Skin Pharmacology and Physiology     Full-text available via subscription   (Followers: 6)
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 6)
Current Drug Discovery Technologies     Hybrid Journal   (Followers: 6)
Current Therapeutic Research     Open Access   (Followers: 6)
Expert Review of Cardiovascular Therapy     Full-text available via subscription   (Followers: 6)
Current Drug Delivery     Hybrid Journal   (Followers: 6)
Current Drug Metabolism     Hybrid Journal   (Followers: 5)
Investigational New Drugs     Hybrid Journal   (Followers: 5)
Toxicon     Hybrid Journal   (Followers: 5)
Medicinal Research Reviews     Hybrid Journal   (Followers: 5)
Anti-Infective Agents     Hybrid Journal   (Followers: 5)
Expert Review of Anti-infective Therapy     Full-text available via subscription   (Followers: 5)
Expert Review of Molecular Diagnostics     Full-text available via subscription   (Followers: 5)
Current Cancer Therapy Reviews     Hybrid Journal   (Followers: 5)
Neuropharmacology     Hybrid Journal   (Followers: 5)
Fitoterapia     Hybrid Journal   (Followers: 5)
Immunopharmacology and Immunotoxicology     Hybrid Journal   (Followers: 4)
Journal of Cardiovascular Pharmacology and Therapeutics     Hybrid Journal   (Followers: 4)
Planta Medica     Hybrid Journal   (Followers: 4)
Current Vascular Pharmacology     Hybrid Journal   (Followers: 4)
Reviews of Physiology, Biochemistry and Pharmacology     Hybrid Journal   (Followers: 4)
Journal of Child and Adolescent Psychopharmacology     Hybrid Journal   (Followers: 4)
International Journal of Pharmaceutical and Healthcare Marketing     Hybrid Journal   (Followers: 4)
Pharmaceutical Medicine     Full-text available via subscription   (Followers: 4)
Journal of Pain Management & Medicine     Open Access   (Followers: 4)
Cancer Chemotherapy and Pharmacology     Hybrid Journal   (Followers: 4)
Journal of Labelled Compounds and Radiopharmaceuticals     Hybrid Journal   (Followers: 4)
Inpharma Weekly     Full-text available via subscription   (Followers: 4)
Inflammation Research     Hybrid Journal   (Followers: 4)
CNS Drug Reviews     Open Access   (Followers: 4)
Therapeutic Drug Monitoring     Hybrid Journal   (Followers: 3)
Research in Social and Administrative Pharmacy     Hybrid Journal   (Followers: 3)
Current Drug Therapy     Hybrid Journal   (Followers: 3)
Chemotherapy     Full-text available via subscription   (Followers: 3)
Cardiovascular Therapeutics     Open Access   (Followers: 3)
International Journal of Neuropsychopharmacology     Open Access   (Followers: 3)
Pharmacopsychiatry     Hybrid Journal   (Followers: 3)
Pharmacology & Therapeutics     Hybrid Journal   (Followers: 3)
ASSAY and Drug Development Technologies     Hybrid Journal   (Followers: 3)
Physiology International     Full-text available via subscription   (Followers: 3)
Journal of Aerosol Medicine and Pulmonary Drug Delivery     Hybrid Journal   (Followers: 3)
Human Psychopharmacology Clinical and Experimental     Hybrid Journal   (Followers: 3)
Frontiers in Medicinal Chemistry     Hybrid Journal   (Followers: 3)
Acta Pharmacologica Sinica     Hybrid Journal   (Followers: 3)
Drug Resistance Updates     Hybrid Journal   (Followers: 3)
Microbial Drug Resistance     Hybrid Journal   (Followers: 3)
Journal of Infection and Chemotherapy     Hybrid Journal   (Followers: 3)
Journal of Ethnopharmacology     Hybrid Journal   (Followers: 3)
Current Pharmacogenomics and Personalized Medicine     Hybrid Journal   (Followers: 3)
Canadian Journal of Physiology and Pharmacology     Hybrid Journal   (Followers: 2)
International Immunopharmacology     Hybrid Journal   (Followers: 2)
Journal of Drug Targeting     Hybrid Journal   (Followers: 2)
BMC Pharmacology     Open Access   (Followers: 2)
Vascular Pharmacology     Hybrid Journal   (Followers: 2)
Journal of Inflammation     Open Access   (Followers: 2)
Biomedicine & Pharmacotherapy     Full-text available via subscription   (Followers: 2)
Clinical Neuropharmacology     Hybrid Journal   (Followers: 2)
Toxicological & Environmental Chemistry     Hybrid Journal   (Followers: 2)
Inflammopharmacology     Hybrid Journal   (Followers: 2)
The Brown University Psychopharmacology Update     Hybrid Journal   (Followers: 2)
Behavioural Pharmacology     Hybrid Journal   (Followers: 2)
Archiv der Pharmazie     Hybrid Journal   (Followers: 2)
Fundamental & Clinical Pharmacology     Hybrid Journal   (Followers: 2)
International Clinical Psychopharmacology     Hybrid Journal   (Followers: 2)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
Pharmacological Reviews     Hybrid Journal   (Followers: 2)
Molecular Pharmacology     Hybrid Journal   (Followers: 2)
Pharmacology Biochemistry and Behavior     Hybrid Journal   (Followers: 2)
Journal of Microencapsulation: Microcapsules, Liposomes, Nanoparticles, Microcells, Microspheres     Hybrid Journal   (Followers: 2)
Letters in Drug Design & Discovery     Hybrid Journal   (Followers: 2)
Drugs in R & D     Full-text available via subscription   (Followers: 2)
Journal of Neuroimmune Pharmacology     Hybrid Journal   (Followers: 1)
Current Pharmaceutical Analysis     Hybrid Journal   (Followers: 1)
Current Enzyme Inhibition     Hybrid Journal   (Followers: 1)
Journal of Texture Studies     Hybrid Journal   (Followers: 1)
Pharmacogenetics and Genomics     Hybrid Journal   (Followers: 1)
Particulate Science and Technology: An International Journal     Hybrid Journal   (Followers: 1)
Current Neuropharmacology     Hybrid Journal   (Followers: 1)
Pharmacological Research     Hybrid Journal   (Followers: 1)
Pharmaceutical Biology     Open Access  
Journal of Liposome Research     Hybrid Journal  
Toxin Reviews     Hybrid Journal  
Kaohsiung Journal of Medical Sciences     Open Access  
Redox Report     Open Access  
Pharmacology     Full-text available via subscription  
PharmacoEconomics & Outcomes News     Full-text available via subscription  
Pharmaceutical Chemistry Journal     Hybrid Journal  
NeuroMolecular Medicine     Hybrid Journal  
Journal of Ocular Pharmacology and Therapeutics     Hybrid Journal  
Harm Reduction Journal     Open Access  
Current Nanoscience     Hybrid Journal  
Infectious Disorders - Drug Targets     Hybrid Journal  
Current Bioactive Compounds     Hybrid Journal  
Cancer Biotherapy & Radiopharmaceuticals     Hybrid Journal  
Autonomic & Autacoid Pharmacology     Hybrid Journal  

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Journal Cover
CNS Drugs
Journal Prestige (SJR): 1.635
Citation Impact (citeScore): 4
Number of Followers: 10  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 1172-7047 - ISSN (Online) 1179-1934
Published by Adis Homepage  [21 journals]
  • Rimegepant: A Review in the Acute Treatment and Preventive Treatment of
           Migraine

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      Abstract: Abstract 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. Rimegepant was also more effective than placebo at reducing the number of monthly migraine days when taken every other day for the preventive treatment of migraine. The beneficial effects of rimegepant in reducing migraine frequency and improving quality of life were maintained over the longer term (up to 52 weeks). Rimegepant was generally well tolerated, with no evidence of hepatotoxicity or cardiovascular toxicity in clinical trials. As the first dual agent approved for both treatment and prevention of migraine, rimegepant represents a useful option for the management of migraine in adults.
      PubDate: 2023-02-04
       
  • Teriflunomide Concentrations in Cerebrospinal Fluid and Plasma in Patients
           with Multiple Sclerosis: A Pharmacokinetic Study

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      Abstract: 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. The objective of this study was to determine the passage of teriflunomide over the blood-cerebrospinal fluid barrier (BCSFB). Methods Plasma and cerebrospinal fluid (CSF) teriflunomide concentrations were determined at steady state in 12 patients with RRMS, treated with oral teriflunomide 14 mg once daily. Included patients were all clinically stable without relapse or disability worsening within 6 months prior from baseline and were on no other immune modulating or immunosuppressive drugs. Results The mean teriflunomide concentrations in plasma and CSF were 38775 (SEM ± 7256) ng/mL and 68 (SEM ± 15) ng/mL, respectively. The passage over the BCSFB was 0.17 % (SEM ± 0.01). While no correlation was found between the function of the BCSFB assessed with the albumin ratio and the CSF teriflunomide concentration, the CSF and plasma teriflunomide concentrations were highly correlated (rs = 0.90, < 0.0001). Conclusions Further studies are warranted to determine if the obtained CSF teriflunomide concentration reflects that in the CNS and is able to influence inflammatory and degenerative processes within the CNS.
      PubDate: 2023-02-02
       
  • The Role of Gut Dysbiosis and Potential Approaches to Target the Gut
           Microbiota in Multiple Sclerosis

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      Abstract: Abstract 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.
      PubDate: 2023-01-24
       
  • Ketamine and Zinc: Treatment of Anorexia Nervosa Via Dual NMDA Receptor
           Modulation

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      Abstract: Abstract 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. The existing magnetic resonance spectroscopy literature in anorexia nervosa is reviewed and we outline the brain region-specific neurometabolite changes that have been reported and their connection to anorexia nervosa psychopathology. Considering the proposed role of dysfunctional neurotransmission in anorexia nervosa, the potential utility of zinc supplementation and sub-anaesthetic doses of ketamine in normalising this is discussed with reference to previous research in anorexia nervosa and other neuropsychiatric conditions. The rationale for future research to investigate the combined use of low-dose ketamine and zinc supplementation to potentially extend the therapeutic benefits in anorexia nervosa is subsequently explored and promising biological markers for assessing and potentially predicting treatment response are outlined.
      PubDate: 2023-01-22
       
  • Switching OnabotulinumtoxinA to Monoclonal Anti-CGRP Antibodies in
           Drug-Resistant Chronic Migraine

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      Abstract: 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. Methods A monocentric, cohort study, enrolling patients with CM, resistant to several preventive treatments, first treated with BTX-A and then with anti-CGRP mAbs with two observational phases of 9 months preceded by respective baseline. First, the retention rate and effectiveness of both treatments were measured in all patients. A second analysis assessed effectiveness in patients stratified according to <50 or <30% response rate to BTX-A. The absolute change from baseline in monthly headache days (MHDs), response rate, analgesic use, and persistence in medication overuse (MO) at 3, 6, and 9 months of treatment were recorded. Last observation carried forward (LOCF) analyses, including all patients and assuming no further changes after discontinuation, were performed for all outcomes. Results Of the 78 enrolled patients (80.8% female, and 89.7% with MO at baseline), 32 (41.0%) received erenumab, 32 (41.0%) galcanezumab, and 14 (18.0%) fremanezumab. Retention rate was 62.2 and 91.0% for BTX-A and 76.9 and 96.2%, for anti-CGRP mAbs at 3 and 9 months of treatment, respectively. At 9 months of treatment, 22.4% of BTX-A patients and 65.0% of anti-CGRP mAbs patients achieved a ≥50% response rate. Anti-CGRP mAbs reduced MHDs, AMN, and AMDs, and decreased the number of MO patients at 9 months. In patients stratified according to <50 or <30% response rate to BTX-A, response rate (≥50% response at 9 months) to anti-CGRP was 62.9 and 57.9%, respectively. LOCF analyses confirmed these findings. No serious adverse events (AEs) were recorded and only two patients discontinued treatment due to AEs. Conclusions Difficult-to-treat CM patients who discontinued BTX-A and received anti-CGRP mAbs showed a substantial clinical improvement in migraine-related outcomes. Switching to an anti-CGRP mAb appears to be a viable option in patients with insufficient response after the first 2 cycles with BTX-A. The appropriate variables, cut-offs, and timing to define ineffectiveness and the best time to switch or combine therapies for difficult-to-treat CM need to be investigated further.
      PubDate: 2023-01-19
       
  • Apixaban for the Treatment of Cerebral Venous Sinus Thrombosis: A
           Single-Centre Experience and Systematic Review of the Literature

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      Abstract: 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. Results Four male patients (average age 43.5 years) with idiopathic CVT, who presented with a headache and/or seizure without neurological deficits/symptoms or cerebral infarcts/haemorrhage were treated with apixaban 5 mg twice daily for an average 28 months (18–46 months) and followed for on average 2.8 years. In two patients, a partial/complete recanalisation was achieved, there was no recurrent CVT, all patients achieved a modified Rankin score of 0, none experienced an intracranial haemorrhage, other bleedings or died. One patient, in whom anti-phospholipid syndrome was later diagnosed, had a recurrence of CVT after stopping apixaban. Our systematic review identified only 15 eligible patients (average age 39 years, 60% female). Partial/complete recanalisation was achieved in 74% of cases, there was no recurrent CVT, 95% achieved a modified Rankin score of ≤ 2, none experienced an intracranial haemorrhage, other bleedings or died. Conclusions Our cases and the review of similar published cases, albeit obtained on a smaller scale, suggest that apixaban may be a safe and effective therapy for CVT. This assumption should be tested in a large randomised study.
      PubDate: 2023-01-17
       
  • Treatment of Patients with Multiple Sclerosis Transitioning Between
           Relapsing and Progressive Disease

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      Abstract: Abstract 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. This review summarizes primary and secondary analyses and reports derived from phase III prospective clinical RCTs listed in PubMed of compounds authorised through the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of MS. The best data are available for interferon beta-1a (IFNb-1a) subcutaneous (s.c.), IFNb-1b s.c., mitoxantrone and siponimod, the latter being the most modern compound with likely the best risk-to-effect ratio. Moreover, there is a labels discrepancy for many disease-modifying treatments (DMTs) between the FDA and EMA, which have to be taken into consideration when opting for a specific DMT.
      PubDate: 2023-01-04
       
  • Treatment Outcomes of Newly Diagnosed Epilepsy: A Systematic Review and
           Meta-analysis

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      Abstract: 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. Proportions of patients seizure free at different follow-up timepoints and their characteristics at the study population level were extracted. The patients were group-wise aggregated using a random-effects model. Primary outcomes were proportions of patients with cumulative 1-year seizure freedom (C1YSF), and 1-year and 5-year terminal seizure freedom (T1YSF and T5YSF). Secondary outcomes included the proportions of patients with early sustained seizure freedom, drug-resistant epilepsy and seizure-free off antiseizure medication at the last follow-up (off antiseizure medications). A separate random-effects meta-analysis was performed for nine predictors of importance. Results In total, 39 cohorts (total n = 21,139) met eligibility criteria. They included 15 predominantly adult cohorts (n = 12,024), 19 children (n = 6569), and 5 of mixed-age groups (n = 2546). The pooled C1YSF was 79% (95% confidence interval [CI] 74–83). T1YSF was 68% (95% CI 63–72) and T5YSF was 69% (95% CI 62–75). Children had higher C1YSF (85% vs 68%, p < 0.001) and T1YSF than adult cohorts (74% vs 61%, p = 0.007). For secondary outcomes, 33% (95% CI 27–39) of patients achieved early sustained seizure freedom, 17% (95% CI 13–21) developed drug resistance, and 39% (95% CI 30–50) were off antiseizure medications at the last follow-up. Studies with a longer follow-up duration correlated with higher C1YSF (p < 0.001) and being off antiseizure medications (p = 0.045). Outcomes were not associated with study design (prospective vs retrospective), cohort size, publication year, or the earliest date of recruitment. Predictors of importance in newly diagnosed epilepsy include etiology, epilepsy type, abnormal diagnostics (neuroimaging, examination, and electroencephalogram findings), number of seizure types, and pre-treatment seizure burden. Conclusions Seizure freedom is achieved with currently available antiseizure medications in most patients with newly diagnosed epilepsy, yet this is often not immediate, may not be sustainable, and has not improved over recent decades. Symptomatic etiology, abnormal neuro-diagnostics, and increased pre-treatment seizure burden and seizure types are important predictors for unfavorable outcomes in newly diagnosed epilepsy. The study findings may be used as a quantitative benchmark on the efficacy of future antiseizure medication therapy for this patient population.
      PubDate: 2022-12-21
       
  • Early Morning ADHD Symptoms and Functional Impairment: Impact on Patients
           and Caregivers, and Pharmacological Approaches to Management

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      Abstract: Abstract 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. Herein, we present a narrative review on early morning functioning impairment in children and adolescents with ADHD, its impact on caregivers, the rating scales available for clinicians to identify the degree of early morning functioning impairment, and the efficacy of currently available treatments in providing functional improvements to patients with ADHD during the early morning, identifying that only treatments that are available upon awakening have been shown to statistically separate from placebo for early morning functioning improvement.
      PubDate: 2022-12-15
       
  • Estimating Risk of Antidepressant Withdrawal from a Review of Published
           Data

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      Abstract: Abstract 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. We searched PubMed for relevant systematic reviews and other relevant analyses to summarise existing data on determinants of antidepressant withdrawal incidence, severity and duration. Overall, data were limited. From survey data, increased duration of use was associated with an increased incidence and severity of withdrawal effects, consistent with some evidence from data provided by drug manufacturers. Duration of use may be related to duration of withdrawal effects but data are heterogenous and sparse. Serotonin and noradrenaline reuptake inhibitors and paroxetine are associated with higher risks than other antidepressants, though data for some antidepressants are lacking. Higher doses of antidepressant has some weak association with an increased risk of withdrawal, with some ceiling effects, perhaps reflecting receptor occupancy relationships. Past experience of withdrawal effects is known to predict future risk. Based on these data, we outline a preliminary rubric for determining the risk of withdrawal symptoms for a particular patient, which may have relevance for determining tapering rates. Given the limited scope of the current research, future research should aim to clarify prediction of antidepressant withdrawal risk, especially by examining the risk of withdrawal in long-term users of medication, as well as the severity and duration of effects, to improve the preliminary tool for predictive purposes. Further research into the precise adaptations in long-term antidepressant use may improve the ability to predict withdrawal effects for a particular patient.
      PubDate: 2022-12-14
       
  • A 10-Year Observational Study of the Use, Acceptability and Effectiveness
           of Long-Acting Paliperidone Palmitate: Implications for Clinical Decision
           Making

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      Abstract: 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. The study evaluated the retention and hospitalization rates 5 years following initiation of PP1M in a naturalistic patient cohort of all adult patients who were newly initiated on PP1M between 2011 and 2015. Electronic records were used to compare the frequency and length of hospital admissions in the 5 years before and after introduction of PP1M. Switching and discontinuation rates and reasons were also recorded with a separate analysis of patients who continued and discontinued PP1M during the study period. Results A total of 167 patients were included in the study (70% with schizophrenia, 30% with other diagnoses). Discontinuation rates were 24%, 15%, 17%, 5% and 8% in years 1–5, respectively; poor tolerability was the most common cause for stopping PP1M. Demographic and clinical factors such as age, sex, diagnosis and care setting did not discriminate between continuers and discontinuers. The group that completed 5 years on PP1M (46%) showed an overall reduction of 72% in the mean number and 68% in the mean length of admissions compared to the 5-year period before initiation, with more than half of the patients requiring no admission at all during this period of time (median = 0). On the contrary, discontinuers demonstrated worse outcomes in overall bed occupancy than continuers. Findings were overall similar across the total cohort and schizophrenia-only group. Conclusions Our study has one of the longest durations of follow up of a naturalistic cohort treated with LAIs confirming sustained improvements for patients who continued treatment for up to 5 years with implicit implications for cost effectiveness. Study findings may facilitate shared decision making in this area, overcoming some of the common barriers for use.
      PubDate: 2022-12-10
       
  • Long-Term Safety and Tolerability of Daridorexant in Patients with
           Insomnia Disorder

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      Abstract: 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. Patients originally randomised to daridorexant (10 mg/25 mg/50 mg) remained on their respective treatments; patients randomised to placebo were re-randomised to daridorexant 25 mg or placebo. The 40-week treatment period was followed by a 7-day placebo run-out. The primary objective was to assess safety/tolerability. Exploratory objectives were to evaluate the efficacy of daridorexant on sleep (self-reported total sleep time) and daytime functioning (Insomnia Daytime Symptoms and Impacts Questionnaire). Results In total, 804 patients were enrolled in the study, of whom 801 received at least one dose of the study treatment and 550 patients (68.4%) completed the study. Overall incidence of treatment-emergent adverse events was similar across groups (35–40%). Daridorexant did not induce next-morning sleepiness and no withdrawal-related symptoms or rebound were observed after treatment discontinuation. Improvements in sleep and daytime functioning were maintained through to the end of the study and were most pronounced with daridorexant 50 mg. Daridorexant 50 mg, compared with placebo, increased self-reported total sleep time by a least-squares mean of 20.4 (95% confidence interval [CI] 4.2, 36.5), 15.8 (95% CI − 0.8, 32.5) and 17.8 (95% CI − 0.4, 35.9) minutes and decreased (i.e., improved) Insomnia Daytime Symptoms and Impacts Questionnaire total scores by a least-squares mean of − 9.3 (95% CI − 15.1, − 3.6), − 9.5 (95% CI − 15.4, − 3.5) and − 9.1 (95% CI − 15.6, − 2.7), at weeks 12, 24 and 36 of the extension study, respectively. Conclusions Treatment with daridorexant, for up to 12 months, was generally safe and well tolerated. Exploratory efficacy analyses suggest that the sustained improvements in sleep and daytime functioning with daridorexant 50 mg support its use for long-term treatment of insomnia disorder, without concerns of new safety signals. Clinical Trial Registration ClinicalTrials.gov (NCT03679884) [first posted: 21 September, 2018], https://clinicaltrials.gov/ct2/show/NCT03679884.
      PubDate: 2022-12-09
       
  • Leveraging Molecular and Immune-Based Therapies in Leptomeningeal
           Metastases

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      Abstract: Abstract Leptomeningeal metastases represent an aggressive stage of cancer with few durable treatment options. Improved understanding of cancer biology, neoplastic reliance on oncogenic driver mutations, and complex immune system interactions have resulted in an explosion in cancer-directed therapy in the last two decades to include small molecule inhibitors and immune checkpoint inhibitors. Most of these therapeutics are underexplored in patients with leptomeningeal metastases, limiting extrapolation of extracranial and even intracranial efficacy outcomes to the unique leptomeningeal space. Further confounding our interpretation of drug activity in the leptomeninges is an incomplete understanding of drug penetration through the blood–cerebrospinal fluid barrier of the choroid plexus. Nevertheless, a number of retrospective studies and promising prospective trials provide evidence of leptomeningeal activity of several small molecule and immune checkpoint inhibitors and underscore potential areas of further therapeutic development for patients harboring leptomeningeal disease.
      PubDate: 2022-12-06
       
  • Orexin Receptor Antagonists in the Treatment of Depression: A Leading
           Article Summarising Pre-clinical and Clinical Studies

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      Abstract: Abstract 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. Three dual orexin receptor antagonists (DORAs) have received licences for treatment of primary insomnia and some ORAs have since been investigated as potential treatments for major depressive disorder (MDD). In this leading article, we summarise the existing literature on use of ORAs in depression, in pre-clinical and clinical studies. In rodent models of depression, investigated ORAs have included the DORA almorexant and TCS1102, the selective orexin 1 receptor antagonists SB334867 and SB674042 and the selective orexin 2 receptor antagonists LSN2424100, MK-1064 and TCS-OX2-29. These pre-clinical studies suggest a possible antidepressant effect of systemic DORA treatment, however the evidence from selective ORAs is conflicting. To date, four published RCTs (one with the DORA filorexant and three with the selective orexin 2 receptor antagonist seltorexant), have compared an ORA with placebo in the treatment of MDD. Only one of these demonstrated a statistically significant difference relative to placebo.
      PubDate: 2022-11-27
       
  • Comparative Effectiveness of Device-Aided Therapies on Quality of Life and
           Off-Time in Advanced Parkinson’s Disease: A Systematic Review and
           Bayesian Network Meta-analysis

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      Abstract: Introduction Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson’s disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD. Methods A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson’s Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson’s Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness. Results A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5–70.9 years, duration of PD was 9.1–15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL. Conclusions This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.
      PubDate: 2022-11-21
       
  • A Multicenter, Randomized, Double-Blind, Positive-Controlled,
           Non-Inferiority, Phase III Clinical Trial Evaluating the Efficacy and
           Safety of Emulsified Isoflurane for Anesthesia Induction in Patients

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      Abstract: Background Emulsified isoflurane was designed to circumvent the deficiencies of inhalation anesthetics, which have a longer time to onset, result in a higher drug consumption, and for which a specific anesthesia machine is required for clinical use. The aim of this study was to compare the efficacy and safety of emulsified isoflurane with propofol for anesthesia induction in adults patients. Methods This multicenter, randomized, double-blind, positive-controlled, non-inferiority, phase III clinical trial compared the efficacy and safety of emulsified isoflurane with propofol for anesthesia induction. Each patient in the emulsified isoflurane group received a single bolus injection of 12% emulsified isoflurane at a dose of 30 mg/kg, and each patient in the propofol group received a single bolus injection of 0.8% propofol at a dose of 2 mg/kg. The primary outcome of the efficacy evaluation was the proportion of participants with successful anesthesia induction, which was regarded as a Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score of < 1 and lack of use of other sedative drugs. A number of secondary efficacy outcomes were also assessed. Safety was monitored based on (1) adverse events, (2) repeated measurement of vital signs; (3) physical examination, (4) routine laboratory examinations of hematology, biochemistry, urine, coagulation function, and (5) 12-lead electrocardiogram. Results A total of 416 patients were enrolled (n = 208 in each group) and 398 patients were administered study drug. The proportion of participants with successful anesthesia induction was 100% with a 95% confidence interval of − 1.9% to + 1.9% for the emulsified isoflurane and propofol groups, which met the predesigned non-inferiority criteria of 5%. The study demonstrated the non-inferiority of sedation produced by emulsified isoflurane compared to propofol. Among the secondary efficacy outcomes, emulsified isoflurane showed a better cardiovascular stability than propofol. The number of patients from the emulsified isoflurane group who experienced drug-related adverse events was significantly higher than that of patients from the propofol group. However, there was no significant difference between the two groups in terms of adverse events or drug-related adverse events of grades 3–5. Conclusions Emulsified isoflurane exhibited non-inferiority of anesthesia/sedation compared to propofol in patients undergoing anesthesia induction. Clinical Trial Registration ChiCTR2000038185, registered on 12 December, 2020 (www.chictr.org.cn).
      PubDate: 2022-11-16
       
  • High-Efficacy Therapies for Treatment-Naïve Individuals with
           Relapsing–Remitting Multiple Sclerosis

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      Abstract: Abstract There are > 18 distinct disease-modifying therapy (DMT) options covering 10 mechanisms of action currently approved by the US Food and Drug Administration for the treatment of relapsing–remitting multiple sclerosis (RRMS). Given the multitude of available treatment options, and recent international consensus guidelines offering differing recommendations, there is broad heterogeneity in how the DMTs are used in clinical practice. Choosing a DMT for newly diagnosed patients with MS is currently a topic of significant debate in MS care. Historically, an escalation approach to DMT was used for newly diagnosed patients with RRMS. However, the evidence for clinical benefits of early treatment with high-efficacy therapies (HETs) in this population is emerging. In this review, we provide an overview of the DMT options and MS treatment strategies, and discuss the clinical benefits of HETs (including ofatumumab, ocrelizumab, natalizumab, alemtuzumab, and cladribine) in the early stages of MS, along with safety concerns associated with these DMTs. By minimizing the accumulation of neurological damage early in the disease course, early treatment with HETs may enhance long-term clinical outcomes over the lifetime of the patient.
      PubDate: 2022-11-09
       
  • Acknowledgement to Referees

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      PubDate: 2022-11-07
       
  • Comment on: “A Phase III, Randomized, Double-Blind, Placebo-Controlled
           Trial Assessing the Efficacy and Safety of Viloxazine Extended-Release
           Capsules in Adults with Attention Deficit/Hyperactivity Disorder”

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      PubDate: 2022-11-04
       
  • Authors’ Reply to Singh and Balasundaram: Comment on “A Phase III,
           Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Efficacy
           and Safety of Viloxazine Extended-Release Capsules in Adults with
           Attention-Deficit/Hyperactivity Disorder”

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      PubDate: 2022-11-04
       
 
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