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Experimental Neurology Jan 2023Antiseizure medications (ASMs) are the mainstay for the treatment of seizure disorders. However, about one-third of people with epilepsy remain refractory to current... (Meta-Analysis)
Meta-Analysis
Antiseizure medications (ASMs) are the mainstay for the treatment of seizure disorders. However, about one-third of people with epilepsy remain refractory to current ASMs. Cannabidiol (CBD) has recently been approved as ASM for three refractory epilepsy syndrome indications in children and adults. In this study, we evaluated the overall clinical potential of an oral CBD to treat refractory epilepsy in patients with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC) through a systematic review and meta-analysis. A comprehensive search of databases was conducted, including randomized controlled trials (RCTs) assessing the effect of CBD in epilepsy patients. The review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review focused on RCTs involving patients receiving highly purified oral CBD (Epidiolex, 10 to 50 mg/kg/day) for up to 16 weeks. A subgroup analysis by syndrome and CBD with or without concomitant clobazam was conducted. The key outcomes were reduction in seizure frequency, differences in 50% responder rates, adverse events, and interactions with clobazam as co-therapy. Odds ratio (OR) with 95% confidence interval (CI) were estimated. Of 1183 articles screened, we included 6 RCTs meeting our eligibility criteria. All studies were considered to have a low risk of bias. In the pooled analysis, CBD treatment was found to be more efficacious compared to placebo (OR = 2.45, 95% CI =1.81-3.32, p < 0.01). Subgroup analysis by syndrome demonstrated the odds of ≥50% reduction in seizures with CBD treatment in patients with DS (OR = 2.26, 95% CI:1.38-3.70), LGS (OR = 2.98, 95% CI:1.83-4.85) and TSC (OR = 1.99, 95% CI = 1.06-3.76). Compared with placebo, CBD was associated with increased adverse events (OR = 1.81, 95% CI = 1.33-2.46) such as diarrhea, somnolence, and sedation, and any serious adverse events (OR = 2.86, 95% CI = 1.63-5.05). Other factors, including dosage and clobazam co-therapy, were significantly associated with a greater effect on seizure control and side effects of CBD. In conclusion, the study shows that CBD is highly efficacious both as standalone and adjunct therapy with clobazam for controlling seizures in DS, LGS, and TSC conditions while limiting side effects. Further pharmacodynamic investigation of CBD actions, drug interaction assessments, and therapeutic management guidelines are warranted.
Topics: Adult; Child; Humans; Anticonvulsants; Cannabidiol; Clobazam; Drug Resistant Epilepsy; Epilepsies, Myoclonic; Epilepsy; Lennox Gastaut Syndrome; Seizures; Treatment Outcome
PubMed: 36206805
DOI: 10.1016/j.expneurol.2022.114238 -
Journal of Affective Disorders Oct 2023The concurrent assessment of weight and affective psychopathology outcomes relevant to the psychopharmacology of major eating disorders (EDs), namely anorexia nervosa... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The concurrent assessment of weight and affective psychopathology outcomes relevant to the psychopharmacology of major eating disorders (EDs), namely anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), warrants systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
PubMed, Scopus, and ClinicalTrials.gov were inquired from inception through August 31st, 2022, for RCTs documenting any psychopharmacological intervention for EDs diagnosed according to validated criteria and reporting weight and psychopathology changes. Adopted keywords were: "anorexia nervosa," "bulimia nervosa," "binge eating disorder," "antidepressant," "antipsychotic," and "mood stabilizer." No language restriction applied.
RESULTS
5122 records were identified, and 203 full-texts were reviewed. Sixty-two studies entered the qualitative synthesis (AN = 22, BN = 23, BED = 17), of which 22 entered the meta-analysis (AN = 9, BN = 10, BED = 3). Concerning BMI increase in AN, olanzapine outperformed placebo (Hedges'g = 0.283, 95%C·I. = 0.051-0.515, I = 0 %; p = .017), whereas fluoxetine failed (Hedges'g = 0.351, 95%C.I. = -0.248 to 0.95, I = 63.37 %; p = .251). Fluoxetine not significantly changed weight (Hedges'g = 0.147, 95%C.I. = -0.157-0.451, I = 0 %; p = .343), reducing binging (Hedges'g = 0.203, 95%C.I. = 0.007-0.399, I = 0 %; p = .042), and purging episodes (Hedges'g = 0.328, 95%C.I. = -0.061-0.717, I = 58.97 %; p = .099) in BN. Lisdexamfetamine reduced weight (Hedges'g = 0.259, 95%C.I. = 0.071-0.446, I = 0 %; p = .007) and binging (Hedges'g = 0.571, 95%C.I. = 0.282-0.860, I = 53.84 %; p < .001) in BED.
LIMITATIONS
Small sample size, short duration, and lack of reliable operational definitions affect most of the included sponsored RCTs.
CONCLUSIONS
The efficacy of different drugs varies across different EDs, warranting additional primary studies recording broad psychopathological and cardiometabolic outcomes besides weight, especially against established psychotherapy interventions.
Topics: Humans; Fluoxetine; Psychopharmacology; Randomized Controlled Trials as Topic; Feeding and Eating Disorders; Bulimia Nervosa; Binge-Eating Disorder; Anorexia Nervosa; Antipsychotic Agents
PubMed: 37393954
DOI: 10.1016/j.jad.2023.06.068 -
Psychiatry Research Jan 2021Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present... (Meta-Analysis)
Meta-Analysis
Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present an update of our previously published algorithms for the use of psychopharmacologic agents in these patients taking into account more recent studies and findings in meta-analyses, reviews, and other published algorithms. We propose three algorithms: BPSD in an emergent, urgent, and non-urgent setting. In the emergent setting when intramuscular (IM) administration is necessary, the first-line recommendation is for olanzapine (since IM aripiprazole, previously favored, is no longer available) and haloperidol injection is the second choice, followed by possible consideration of an IM benzodiazepine. In the urgent setting, the first line would be oral second-generation antipsychotics (SGAs) aripiprazole and risperidone. Perhaps next could be then prazosin, and lastly electroconvulsive therapy is a consideration. There are risks associated with these agents, and adverse effects can be severe. Dosing strategies, discontinuation considerations, and side effects are discussed. In the non-emergent setting, medications are proposed for use in the following order: trazodone, donepezil and memantine, antidepressants such as escitalopram and sertraline, SGAs, prazosin, and carbamazepine. Other options with less support but potential future promise are discussed.
Topics: Academic Medical Centers; Aged; Algorithms; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Citalopram; Dementia; Electroconvulsive Therapy; Haloperidol; Humans; Olanzapine; Psychopharmacology; Risperidone
PubMed: 33340800
DOI: 10.1016/j.psychres.2020.113641 -
Neuroscience and Biobehavioral Reviews Aug 2022The use of low doses of psychedelic substances (microdosing) is attracting increasing interest. This systematic review summarises all empirical microdosing research to... (Review)
Review
The use of low doses of psychedelic substances (microdosing) is attracting increasing interest. This systematic review summarises all empirical microdosing research to date, including a set of infrequently cited studies that took place prior to prohibition. Specifically, we reviewed 44 studies published between 1955 and 2021, and summarised reported effects across six categories: mood and mental health; wellbeing and attitude; cognition and creativity; personality; changes in conscious state; and neurobiology and physiology. Studies showed a wide range in risk of bias, depending on design, age, and other study characteristics. Laboratory studies found changes in pain perception, time perception, conscious state, and neurophysiology. Self-report studies found changes in cognitive processing and mental health. We review data related to expectation and placebo effects, but argue that claims that microdosing effects are largely due to expectancy are premature and possibly wrong. In addition, we attempt to clarify definitional inconsistencies in the microdosing literature by providing suggested dose ranges across different substances. Finally, we provide specific design suggestions to facilitate more rigorous future research.
Topics: Affect; Creativity; Hallucinogens; Humans; Mental Health; Personality; Psilocybin
PubMed: 35609684
DOI: 10.1016/j.neubiorev.2022.104706 -
Journal of Clinical Pharmacy and... Jun 2021Meropenem, a carbapenem antibiotic, is widely prescribed for the treatment of life-threatening infections. The main parameter associated with its therapeutic success is...
WHAT IS KNOWN AND OBJECTIVE
Meropenem, a carbapenem antibiotic, is widely prescribed for the treatment of life-threatening infections. The main parameter associated with its therapeutic success is the percentage of time that the levels remain above the minimum inhibitory concentration. Inadequate levels of meropenem can lead to therapeutic failure and increase the possibility of microbial resistance. The employment of strategies involving dose regimens and drug pharmacodynamics has become increasingly important to optimize therapies. In the present study, we conducted a review with the purpose of assembling information about the clinical use of meropenem and therapeutic drug monitoring.
METHODS
A literature review emphasizing the application of therapeutic drug monitoring (TDM) of meropenem in clinical practice has been done. To identify articles related to the topic, we performed a standardized search from January 21, 2020 to December 21, 2020, using specific descriptors in PubMed, Lilacs and Embase.
RESULTS AND DISCUSSION
In total, 35 studies were included in the review. The daily dose of meropenem commonly ranged from 3 to 6 g/day. Critically ill patients and those with impaired renal function appear to be the most suitable patients for the application of meropenem TDM, in order to guide therapy. We observed that most of the studies recommend TDM and that, in nine locations, the TDM of meropenem and of other beta-lactams is a routine practice. TDM data can help to maximize the clinical outcomes of the treatment with meropenem. It can also improve the patient care by providing suitable levels of meropenem, guiding the most appropriate dose regimens, which is the main parameter associated with therapeutic success.
WHAT IS NEW AND CONCLUSION
The findings from this review suggest that the therapeutic monitoring of meropenem can be beneficial, since it adjusts the treatment and aids clinical outcomes. It does so by indicating the appropriate dosage and preventing failure, toxicity and possible antimicrobial resistance. The multidisciplinary effort, basic knowledge and communication among the medical team are also essential.
Topics: Anti-Bacterial Agents; Critical Illness; Drug Monitoring; Drug Resistance, Microbial; Humans; Meropenem; Microbial Sensitivity Tests; Severity of Illness Index
PubMed: 33533509
DOI: 10.1111/jcpt.13369 -
Current Neuropharmacology 2022Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient...
BACKGROUND
Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient treatment, the poor adherence in advanced patients, and varied response. Proper intake of medications regarding food and managing drug-food interactions may optimize Parkinson's disease treatment.
OBJECTIVES
We investigated potential effects that food, beverages, and dietary supplements may have on the pharmacokinetics and pharmacodynamics of drugs used by parkinsonian patients; identified the most probable interactions; and shaped recommendations for the optimal intake of drugs regarding food.
METHODS
We performed a systematic review in adherence to PRISMA guidelines, and included a total of 81 studies in the qualitative synthesis.
RESULTS AND CONCLUSION
We found evidence for levodopa positive interaction with coffee, fiber and vitamin C, as well as for the potential beneficial impact of low-fat and protein redistribution diet. Contrastingly, high-protein diet and ferrous sulfate supplements can negatively affect levodopa pharmacokinetics and effectiveness. For other drugs, the data of food impact are scarce. Based on the available limited evidence, all dopamine agonists (bromocriptine, cabergoline, ropinirole), tolcapone, rasagiline, selegiline in tablets, safinamide, amantadine and pimavanserin can be taken with or without a meal. Opicapone and orally disintegrating selegiline tablets should be administered on an empty stomach. Of monoamine oxidase B inhibitors, safinamide is the least susceptible for interaction with the tyramine-rich food, whereas selegiline and rasagiline may lose selectivity to monoamine oxidase B when administered in supratherapeutic doses. The level of presented evidence is low due to the poor studies design, their insufficient actuality, and missing data.
Topics: Antiparkinson Agents; Dietary Supplements; Humans; Levodopa; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline
PubMed: 34784871
DOI: 10.2174/1570159X19666211116142806 -
International Journal of Antimicrobial... May 2021The superiority of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro models may predict the efficacy... (Meta-Analysis)
Meta-Analysis
The superiority of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro models may predict the efficacy of antibiotic regimens against CR-GNB. A systematic review and meta-analysis was performed including pharmacokinetic/pharmacodynamic (PK/PD) and time-kill (TK) studies examining the in vitro efficacy of antibiotic combinations against CR-GNB [PROSPERO registration no. CRD42019128104]. The primary outcome was in vitro synergy based on the effect size (ES): high, ES ≥ 0.75, moderate, 0.35 < ES < 0.75; low, ES ≤ 0.35; and absent, ES = 0). A network meta-analysis assessed the bactericidal effect and re-growth rate (secondary outcomes). An adapted version of the ToxRTool was used for risk-of-bias assessment. Over 180 combination regimens from 136 studies were included. The most frequently analysed classes were polymyxins and carbapenems. Limited data were available for ceftazidime/avibactam, ceftolozane/tazobactam and imipenem/relebactam. High or moderate synergism was shown for polymyxin/rifampicin against Acinetobacter baumannii [ES = 0.91, 95% confidence interval (CI) 0.44-1.00], polymyxin/fosfomycin against Klebsiella pneumoniae (ES = 1.00, 95% CI 0.66-1.00) and imipenem/amikacin against Pseudomonas aeruginosa (ES = 1.00, 95% CI 0.21-1.00). Compared with monotherapy, increased bactericidal activity and lower re-growth rates were reported for colistin/fosfomycin and polymyxin/rifampicin in K. pneumoniae and for imipenem/amikacin or imipenem/tobramycin against P. aeruginosa. High quality was documented for 65% and 53% of PK/PD and TK studies, respectively. Well-designed in vitro studies should be encouraged to guide the selection of combination therapies in clinical trials and to improve the armamentarium against carbapenem-resistant bacteria.
Topics: Amikacin; Anti-Bacterial Agents; Azabicyclo Compounds; Carbapenems; Ceftazidime; Cephalosporins; Colistin; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; In Vitro Techniques; Microbial Sensitivity Tests; Polymyxins; Rifampin; Tazobactam; Tobramycin
PubMed: 33857539
DOI: 10.1016/j.ijantimicag.2021.106344 -
BMC Infectious Diseases Feb 2021This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety.
METHODS
We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47-0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15-20 μg/mL (OR 2.39, 95% CI 1.78-3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18-0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13-3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28-1.01); however, it was not significant in the analysis of mortality.
CONCLUSIONS
We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.
Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Area Under Curve; Bacteremia; Drug Monitoring; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Odds Ratio; Safety; Staphylococcal Infections; Treatment Failure; Vancomycin
PubMed: 33549035
DOI: 10.1186/s12879-021-05858-6 -
Clinical Pharmacology and Therapeutics Jun 2021Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric...
Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations.
Topics: Cytochrome P-450 CYP2C19; Gastroesophageal Reflux; Genotype; Humans; Pharmacogenetics; Proton Pump Inhibitors
PubMed: 32770672
DOI: 10.1002/cpt.2015 -
Clinical Infectious Diseases : An... Nov 2022Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of... (Meta-Analysis)
Meta-Analysis
Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of TDM-guided dosing on clinical outcomes remains unknown. We conducted a systematic review and meta-analysis on TDM-guided dosing and clinical outcomes (all-cause mortality, clinical cure, microbiological cure, treatment failure, hospital and intensive care unit length of stay, target attainment, antibiotic-related adverse events, and emergence of resistance) in critically ill patients with suspected or proven sepsis. Eleven studies (n = 1463 participants) were included. TDM-guided dosing was associated with improved clinical cure (relative risk, 1.17; 95% confidence interval [CI], 1.04 to 1.31), microbiological cure (RR, 1.14; 95% CI, 1.03 to 1.27), treatment failure (RR, 0.79; 95% CI, .66 to .94), and target attainment (RR, 1.85; 95% CI, 1.08 to 3.16). No associations with mortality and length of stay were found. TDM-guided dosing improved clinical and microbiological cure and treatment response. Larger, prospective, randomized trials are required to better assess the utility of beta-lactam TDM in critically ill patients.
Topics: Humans; Critical Illness; Drug Monitoring; Prospective Studies; beta-Lactams; Anti-Bacterial Agents; Monobactams
PubMed: 35731853
DOI: 10.1093/cid/ciac506