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JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527 -
JAMA Network Open Aug 2023Antiobesity pharmacotherapy is recommended for adolescents ages 12 years and older with obesity. Several medications have been approved by the US Food and Drug...
IMPORTANCE
Antiobesity pharmacotherapy is recommended for adolescents ages 12 years and older with obesity. Several medications have been approved by the US Food and Drug Administration for adolescent use, but the most cost-effective medication remains unclear.
OBJECTIVE
To estimate the cost-effectiveness of lifestyle counseling alone and as adjunct to liraglutide, mid-dose phentermine and topiramate (7.5 mg phentermine and 46 mg topiramate), top-dose phentermine and topiramate (15 mg phentermine and 92 mg topiramate), or semaglutide among adolescent patients with obesity.
DESIGN, SETTING, AND PARTICIPANTS
This economic evaluation used a microsimulation model to project health and cost outcomes of lifestyle counseling alone and adjunct to liraglutide, mid-dose phentermine and topiramate, top-dose phentermine and topiramate, or semaglutide over 13 months, 2 years, and 5 years among a hypothetical cohort of 100 000 adolescents with obesity, defined as an initial body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 37. Model inputs were derived from clinical trials, published literature, and national sources. Data were analyzed from April 2022 to July 2023.
EXPOSURES
Lifestyle counseling alone and as adjunct to liraglutide, mid-dose phentermine and topiramate, top-dose phentermine and topiramate, or semaglutide.
MAIN OUTCOMES AND MEASURES
The main outcome was quality-adjusted life years (QALYs), costs (2022 US dollars), and incremental cost-effectiveness ratios (ICERs), with future costs and QALYs discounted 3.0% annually. A strategy was considered cost-effective if the ICER was less than $100 000 per QALY gained. The preferred strategy was determined as the strategy with the greatest increase in QALYs while being cost-effective. One-way and probabilistic sensitivity analyses were used to assess parameter uncertainty.
RESULTS
The model simulated 100 000 adolescents at age 15 with an initial BMI of 37, of whom 58 000 (58%) were female. At 13 months and 2 years, lifestyle counseling was estimated to be the preferred strategy. At 5 years, top-dose phentermine and topiramate was projected to be the preferred strategy with an ICER of $56 876 per QALY gained vs lifestyle counseling. Semaglutide was projected to yield the most QALYs, but with an unfavorable ICER of $1.1 million per QALY gained compared with top-dose phentermine and topiramate. Model results were most sensitive to utility of weight reduction and weight loss of lifestyle counseling and top-dose phentermine and topiramate.
CONCLUSIONS AND RELEVANCE
In this economic evaluation of pharmacotherapy for adolescents with obesity, top-dose phentermine and topiramate as adjunct to lifestyle counseling was estimated to be cost-effective after 5 years. Long-term clinical trials in adolescents are needed to fully evaluate the outcomes of pharmacotherapy, especially into adulthood.
Topics: United States; Adolescent; Humans; Female; Male; Cost-Benefit Analysis; Pediatric Obesity; Topiramate; Liraglutide; Phentermine
PubMed: 37651143
DOI: 10.1001/jamanetworkopen.2023.29178 -
International Journal of Molecular... Nov 2023Advanced identification of the gene mutations causing epilepsy syndromes is expected to translate into faster diagnosis and more effective treatment of these conditions.... (Review)
Review
Advanced identification of the gene mutations causing epilepsy syndromes is expected to translate into faster diagnosis and more effective treatment of these conditions. Over the last 5 years, approximately 40 clinical trials on the treatment of genetic epilepsies have been conducted. As a result, some medications that are not regular antiseizure drugs (e.g., soticlestat, fenfluramine, or ganaxolone) have been introduced to the treatment of drug-resistant seizures in Dravet, Lennox-Gastaut, maternally inherited chromosome 15q11.2-q13.1 duplication (Dup 15q) syndromes, and protocadherin 19 (PCDH 19)-clusterig epilepsy. And although the effects of soticlestat, fenfluramine, and ganaxolone are described as promising, they do not significantly affect the course of the mentioned epilepsy syndromes. Importantly, each of these syndromes is related to mutations in several genes. On the other hand, several mutations can occur within one gene, and different gene variants may be manifested in different disease phenotypes. This complex pattern of inheritance contributes to rather poor genotype-phenotype correlations. Hence, the detection of a specific mutation is not synonymous with a precise diagnosis of a specific syndrome. Bearing in mind that seizures develop as a consequence of the predominance of excitatory over inhibitory processes, it seems reasonable that mutations in genes encoding sodium and potassium channels, as well as glutamatergic and gamma-aminobutyric (GABA) receptors, play a role in the pathogenesis of epilepsy. In some cases, different pathogenic variants of the same gene can result in opposite functional effects, determining the effectiveness of therapy with certain medications. For instance, seizures related to gain-of-function (GoF) mutations in genes encoding sodium channels can be successfully treated with sodium channel blockers. On the contrary, the same drugs may aggravate seizures related to loss-of-function (LoF) variants of the same genes. Hence, knowledge of gene mutation-treatment response relationships facilitates more favorable selection of drugs for anticonvulsant therapy.
Topics: Humans; Anticonvulsants; Epilepsy; Seizures; Epileptic Syndromes; Genetic Background; Fenfluramine
PubMed: 38003469
DOI: 10.3390/ijms242216280 -
The Korean Journal of Gastroenterology... Mar 2024The prevalence of obesity with various complications is increasing rapidly in Korea. Although lifestyle modification is fundamental in obesity treatment, more effective... (Review)
Review
The prevalence of obesity with various complications is increasing rapidly in Korea. Although lifestyle modification is fundamental in obesity treatment, more effective treatment tools are required. Many advances in obesity treatment have been reported recently, including lifestyle modifications and pharmacological, endoscopic, and surgical treatments. Drugs with proven long-term efficacy and safety are preferred because management for obesity treatment is a long-term process. Currently, four medications are available for long-term use in Korea: Orlistat, Naltrexone/bupuropion NR, Phentermine/topiramate capsule, and Liraglutide. Recently, semaglutide and tirzepatide have been attracting attention because of their effectiveness and convenience, but they are not yet available in Korea. In addition, there are limitations such as the yo-yo effect when discontinuing the drug, long-term safety, and cost. Patients and medical staff must be aware of the advantages and side effects of each medication to ensure the successful treatment of obesity.
Topics: Humans; Anti-Obesity Agents; Phentermine; Obesity; Orlistat; Liraglutide
PubMed: 38522852
DOI: 10.4166/kjg.2024.016 -
Ugeskrift For Laeger Jan 2024This is a case report of two men aged 39 and 43 years with dissection of the coeliac trunk involving the splenic arteries causing splenic infarction. One case was...
This is a case report of two men aged 39 and 43 years with dissection of the coeliac trunk involving the splenic arteries causing splenic infarction. One case was associated with an increase in abdominal pressure during defaecation and the other occurred during treatment with methylphenidate. Based on the published 43 cases, risk factors include male sex, increased intraabdominal pressure or increased vascular pressure. Methylphenidate most likely increased the blood pressure, and dissections of other arteries have been described during treatment with this and the similar drug amphetamine.
Topics: Humans; Male; Amphetamine; Blood Pressure; Celiac Artery; Methylphenidate; Splenic Artery; Adult
PubMed: 38235724
DOI: 10.61409/V07230468 -
Laeknabladid May 2024MDMA is a potential novel treatment for post-traumatic stress disorder (PTSD). Our goal is to review current knowledge on MDMA and its use in MDMA-assisted psychotherapy... (Review)
Review
MDMA is a potential novel treatment for post-traumatic stress disorder (PTSD). Our goal is to review current knowledge on MDMA and its use in MDMA-assisted psychotherapy for PTSD. Literature searches were done on PubMed, Web of Science and Google Scholar and references reviewed in identified articles. MDMA-assisted therapy for PTSD usually consists of a few preparatory sessions before two or three sessions where one or two oral doses of MDMA are given along with supportive psychotherapy. The therapy is delivered in the presence of two therapists for about eight hours each time. In addition, the patient receives up to 9 integrative sessions in due course. This use of MDMA as a part of psychotherapy for PTSD is proposed to lessen the psychological distress that often arises in the processing of traumatic events to facilitate the treatment process and reduce the risk of drop-out. Recent studies indicate that MDMA-assisted psychotherapy reduces PTSD symptoms and is generally well tolerated. These studies are necessary if this MDMA-assisted treatment is to be approved by licensing authorities. There is an urgent need for new effective treatments for PTSD and for comparisons between this MDMA-assisted psychotherapy and currently approved psychotherapies with and without MDMA-use.
Topics: Humans; Stress Disorders, Post-Traumatic; Treatment Outcome; Psychotherapy; N-Methyl-3,4-methylenedioxyamphetamine; Hallucinogens; Combined Modality Therapy
PubMed: 38713560
DOI: 10.17992/lbl.2024.05.793 -
JAMA Network Open Oct 2023Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this...
IMPORTANCE
Although the American Academy of Pediatrics has recommended treatment with antiobesity drugs for adolescents, the cost-effectiveness of antiobesity drugs for this population is still unknown.
OBJECTIVE
To quantify cost-effectiveness of different antiobesity drugs available for pediatric use.
DESIGN, SETTING, AND PARTICIPANTS
This economic evaluation used a Markov microsimulation model with health states defined by obesity levels. Effectiveness was measured by quality-adjusted life-years (QALYs) and costs were calculated from third-party payer perspective, estimated in 2023 US dollars over a 10-year horizon. Data were obtained from the published literature.
INTERVENTION
Antiobesity drugs orlistat, liraglutide, semaglutide, and phentermine-topiramate vs no treatment. Metformin hydrochloride and 2 types of bariatric surgical procedures (sleeve gastrectomy and gastric bypass) were considered in sensitivity analysis.
MAIN OUTCOMES AND MEASURES
Incremental cost-effectiveness ratio.
RESULTS
Among the 4 antiobesity drugs currently approved for pediatric use, phentermine-topiramate was the most cost-effective with an incremental cost-effectiveness ratio of $93 620 per QALY relative to no treatment in this simulated cohort of 10 000 adolescents aged 12 to 17 years (mode, 15 years) with severe obesity (62% female). While semaglutide offered more QALYs than phentermine-topiramate, its higher cost resulted in an incremental cost-effectiveness ratio ($1 079 480/QALY) that exceeded the commonly used willingness-to-pay threshold of $100 000 to $150 000/QALY. Orlistat and liraglutide cost more and were less effective than phentermine-topiramate and semaglutide, respectively. Sleeve gastrectomy and gastric bypass were more effective than phentermine-topiramate but were also more costly, rendering them not cost-effective compared with phentermine-topiramate at the willingness-to-pay threshold of $100 000 to $150 000/QALY.
CONCLUSIONS AND RELEVANCE
In this economic evaluation of weight loss drugs for adolescents with severe obesity, we found phentermine-topiramate to be a cost-effective treatment at a willingness-to-pay threshold of $100 000 to $150 000/QALY. Further research is needed to determine long-term drug efficacy and how long adolescents continue treatment.
Topics: Humans; Female; Adolescent; Child; Male; Anti-Obesity Agents; Obesity, Morbid; Cost-Benefit Analysis; Orlistat; Topiramate; Liraglutide; Obesity; Phentermine
PubMed: 37824146
DOI: 10.1001/jamanetworkopen.2023.36400 -
Journal of Feline Medicine and Surgery Sep 2023Feline inflammatory airway diseases, including (but not limited to) asthma, chronic bronchitis and bronchiectasis, are common and incurable disorders. These diseases... (Review)
Review
PRACTICAL RELEVANCE
Feline inflammatory airway diseases, including (but not limited to) asthma, chronic bronchitis and bronchiectasis, are common and incurable disorders. These diseases require lifelong therapy and may result in substantial morbidity and, in some cases, mortality. Goals of therapy include reduction or resolution of clinical signs and the underlying pathologic processes driving those clinical signs. Inhalational therapy has the advantage of topical delivery of drugs to target tissues at higher doses with fewer systemic effects than oral medications. There are multiple options for delivery devices, and proper selection and training on the use of these devices - including acclimation of the cat to the device - can maximize therapeutic efficacy.
AIM
As inhalational therapy is uncommonly used by many veterinarians and owners, this review article provides a foundation on the selection and use of devices and inhalant medications for specific feline inflammatory airway diseases. Cats present a unique challenge with respect to the use of inhalers, and easy-to-follow steps on acclimating them to the devices are provided. The review also discusses the mechanics of inhalational therapy and helps clarify why certain medications, such as albuterol (salbutamol), fluticasone or budesonide, are chosen for certain diseases. The ultimate aim is that the practitioner should feel more comfortable managing common airway diseases in cats.
EVIDENCE BASE
In compiling their review, the authors searched the veterinary literature for articles in English that discuss inhalational therapy in cats, and which focus primarily on inhaled glucocorticoids and bronchodilators. While most literature on inhalational therapy in cats is based on experimental feline asthma models, there are some studies demonstrating successful treatment in cats with naturally occurring inflammatory airway disease.
Topics: Cats; Animals; Humans; Asthma; Albuterol; Bronchitis, Chronic; Emotions; Veterinarians; Cat Diseases
PubMed: 37675792
DOI: 10.1177/1098612X231193054 -
Scientific Reports Nov 2023Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson's disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors...
Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson's disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.
Topics: Humans; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline; Retrospective Studies; Monoamine Oxidase; Dopamine Agents; Amphetamines
PubMed: 37935702
DOI: 10.1038/s41598-023-44142-2 -
Cell Reports. Medicine Jan 2024Craving is central to methamphetamine use disorder (MUD) and both characterizes the disease and predicts relapse. However, there is currently a lack of robust and...
Craving is central to methamphetamine use disorder (MUD) and both characterizes the disease and predicts relapse. However, there is currently a lack of robust and reliable biomarkers for monitoring craving and diagnosing MUD. Here, we seek to identify a neurobiological signature of craving based on individual-level functional connectivity pattern differences between healthy control and MUD subjects. We train high-density electroencephalography (EEG)-based models using data recorded during the resting state and then calculate imaginary coherence features between the band-limited time series across different brain regions of interest. Our prediction model demonstrates that eyes-open beta functional connectivity networks have significant predictive value for craving at the individual level and can also identify individuals with MUD. These findings advance the neurobiological understanding of craving through an EEG-tailored computational model of the brain connectome. Dissecting neurophysiological features provides a clinical avenue for personalized treatment of MUD.
Topics: Humans; Methamphetamine; Craving; Electroencephalography; Brain
PubMed: 38151021
DOI: 10.1016/j.xcrm.2023.101347