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Clinical Pharmacology and Therapeutics Aug 2020Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used analgesics due to their lack of addictive potential. However, NSAIDs have the potential to... (Meta-Analysis)
Meta-Analysis
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used analgesics due to their lack of addictive potential. However, NSAIDs have the potential to cause serious gastrointestinal, renal, and cardiovascular adverse events. CYP2C9 polymorphisms influence metabolism and clearance of several drugs in this class, thereby affecting drug exposure and potentially safety. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for NSAIDs based on CYP2C9 genotype (updates at www.cpicpgx.org).
Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Decision-Making; Consensus; Cytochrome P-450 CYP2C9; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Phenotype; Predictive Value of Tests; Risk Assessment; Risk Factors
PubMed: 32189324
DOI: 10.1002/cpt.1830 -
European Journal of Human Genetics :... Mar 2024The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to...
The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to optimize pharmacotherapy. A guideline describing the gene-drug interaction between the genes CYP2D6, CYP3A4 and CYP1A2 and antipsychotics is presented here. The DPWG identified gene-drug interactions that require therapy adjustments when respective genotype is known for CYP2D6 with aripiprazole, brexpiprazole, haloperidol, pimozide, risperidone and zuclopenthixol, and for CYP3A4 with quetiapine. Evidence-based dose recommendations were obtained based on a systematic review of published literature. Reduction of the normal dose is recommended for aripiprazole, brexpiprazole, haloperidol, pimozide, risperidone and zuclopenthixol for CYP2D6-predicted PMs, and for pimozide and zuclopenthixol also for CYP2D6 IMs. For CYP2D6 UMs, a dose increase or an alternative drug is recommended for haloperidol and an alternative drug or titration of the dose for risperidone. In addition, in case of no or limited clinical effect, a dose increase is recommended for zuclopenthixol for CYP2D6 UMs. Even though evidence is limited, the DPWG recommends choosing an alternative drug to treat symptoms of depression or a dose reduction for other indications for quetiapine and CYP3A4 PMs. No therapy adjustments are recommended for the other CYP2D6 and CYP3A4 predicted phenotypes. In addition, no action is required for the gene-drug combinations CYP2D6 and clozapine, flupentixol, olanzapine or quetiapine and also not for CYP1A2 and clozapine or olanzapine. For identified gene-drug interactions requiring therapy adjustments, genotyping of CYP2D6 or CYP3A4 prior to treatment should not be considered for all patients, but on an individual patient basis only.
Topics: Humans; Antipsychotic Agents; Aripiprazole; Clopenthixol; Clozapine; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Drug Interactions; Haloperidol; Olanzapine; Pharmacogenetics; Pimozide; Quetiapine Fumarate; Quinolones; Risperidone; Thiophenes
PubMed: 37002327
DOI: 10.1038/s41431-023-01347-3 -
Nutrition and Health Sep 2023Pineapple has an important role in ethnopharmacology and its enzyme, bromelain, has been extensively investigated for its medicinal properties. This systematic review... (Meta-Analysis)
Meta-Analysis Review
Pineapple has an important role in ethnopharmacology and its enzyme, bromelain, has been extensively investigated for its medicinal properties. This systematic review and meta-analysis aimed to assess clinical evidence concerning the efficacy and safety of bromelain. A systematic search was conducted from conception to August 2022 using CINAHL Complete, MEDLINE, ScienceDirect, Scopus, and Thai Journal Online (TJO). The risk of bias was assessed using Risk of Bias 2 or ROBIN-I. A random-effect model with inverse variance weighting and DerSimonian and Laird method was used for meta-analysis. The heterogeneity was evaluated by statistics. We included 54 articles for qualitative summary and 39 articles for meta-analysis. The systematic review found that bromelain presented in serum with retained proteolytic activity after oral absorption. Bromelain may be effective against sinusitis but was not effective for cardiovascular diseases. Pain reduction from oral bromelain was slightly but significantly better than controls (mean difference in pain score = -0.27; 95% CI: -0.45, -0.08; = 9; = 29%). Adverse events included flatulence, nausea, and headache. Topical bromelain significantly reduced the time to complete debridement (mean difference in time = -6.89 days; 95% CI: -7.94, -5.83; = 4; = 2%). Adverse events may be irrelevant and include burning sensation, pain, fever, and sepsis. Moderate-quality studies demonstrated the potential of oral bromelain in pain control and topical bromelain in wound care. Major health risks were not reported during the treatment with bromelain.
Topics: Humans; Bromelains; Ananas; Ethnopharmacology; Pain
PubMed: 37157782
DOI: 10.1177/02601060231173732 -
Progress in Neuro-psychopharmacology &... Aug 2021Autism Spectrum Disorder (ASD) is a severe and lifelong neurodevelopmental disorder, with high social costs and a dramatic burden on the quality of life of patients and...
Autism Spectrum Disorder (ASD) is a severe and lifelong neurodevelopmental disorder, with high social costs and a dramatic burden on the quality of life of patients and family members. Despite its high prevalence, reaching 1/54 children and 1/45 adults in the United States, no pharmacological treatment is still directed to core symptoms of ASD, encompassing social and communication deficits, repetitive behaviors, restricted interests, and abnormal sensory processing. The purpose of this review is to provide an overview of the state-of-the-art of psychopharmacological therapy available today for ASD in children and adolescents, in order to foster best practices and to organize new strategies for future research. To date, atypical antipsychotics such as risperidone and aripiprazole represent the first line of intervention for hyperactivity, impulsivity, agitation, temper outbursts or aggression towards self or others. Tricyclic antidepressants are less prescribed because of uncertain efficacy and important side effects. SSRIs, especially fluoxetine and sertraline, may be effective in treating repetitive behaviors (anxiety and obsessive-compulsive symptoms) and irritability/agitation, while mirtazapine is more helpful with sleep problems. Low doses of buspirone have shown some efficacy on restrictive and repetitive behaviors in combination with behavioral interventions. Stimulants, and to a lesser extent atomoxetine, are effective in reducing hyperactivity, inattention and impulsivity also in comorbid ASD-ADHD, although with somewhat lower efficacy and greater incidence of side effects compared to idiopathic ADHD. Clonidine and guanfacine display some efficacy on hyperactivity and stereotypic behaviors. For several other drugs, case reports and open-label studies suggest possible efficacy, but no randomized controlled trial has yet been performed. Research in the pediatric psychopharmacology of ASD is still faced with at least two major hurdles: (a) Great interindividual variability in clinical response and side effect sensitivity is observed in the ASD population. This low level of predictability would benefit from symptom-specific treatment algorithms and from biomarkers to support drug choice; (b) To this date, no psychoactive drug appears to directly ameliorate core autism symptoms, although some indirect improvement has been reported with several drugs, once the comorbid target symptom is abated.
Topics: Antidepressive Agents, Tricyclic; Antipsychotic Agents; Autism Spectrum Disorder; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Humans; Psychopharmacology; Psychotropic Drugs; Selective Serotonin Reuptake Inhibitors
PubMed: 33857522
DOI: 10.1016/j.pnpbp.2021.110326 -
Expert Opinion on Emerging Drugs Mar 2021The large percentage of adults with major depressive disorder (MDD) insufficiently responding and/or tolerating conventional monoamine-based antidepressants invites the...
INTRODUCTION
The large percentage of adults with major depressive disorder (MDD) insufficiently responding and/or tolerating conventional monoamine-based antidepressants invites the need for mechanistically novel treatments. Convergent evidence implicates glutamatergic signaling as a potential therapeutic target in MDD.
AREAS COVERED
The synthesis herein of preclinical and clinical studies indicates that dextromethorphan (DXM) is well tolerated and exhibits clinically significant antidepressant effects; DXM combined with bupropion has demonstrated replicated and relatively rapid onset efficacy in adults with MDD. DXM efficacy has been preliminarily reported in adults with bipolar depression. The combination of DXM and bupropion represents a pharmacokinetic and pharmacodynamic synergy which may account for the rapidity of action in MDD.
EXPERT OPINION
The combination of DXM and bupropion is a safe, well tolerated and efficacious treatment option in adults with MDD. Priority questions are whether DXM/bupropion is uniquely effective across discrete domains of psychopathology (e.g. anhedonia, reward processing, general cognitive systems) and/or whether it is able to significantly improve patient-reported outcomes (e.g. quality of life, psychosocial functioning). The availability of ketamine/esketamine and DXM/bupropion instantiates the relevance of glutamate as a treatment target in MDD. Studies in bipolar depression with DXM/bupropion are warranted as well as in MDD with suicidality.
Topics: Adult; Animals; Antidepressive Agents; Bipolar Disorder; Bupropion; Depressive Disorder, Major; Dextromethorphan; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Humans; Molecular Targeted Therapy
PubMed: 33682569
DOI: 10.1080/14728214.2021.1898588 -
Journal of Psychopharmacology (Oxford,... Aug 2019This British Association for Psychopharmacology guideline replaces the original version published in 2010, and contains updated information and recommendations. A... (Meta-Analysis)
Meta-Analysis
This British Association for Psychopharmacology guideline replaces the original version published in 2010, and contains updated information and recommendations. A consensus meeting was held in London in October 2017 attended by recognised experts and advocates in the field. They were asked to provide a review of the literature and identification of the standard of evidence in their area, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. Each presentation was followed by discussion, aiming to reach consensus where the evidence and/or clinical experience was considered adequate, or otherwise to flag the area as a direction for future research. A draft of the proceedings was circulated to all speakers for comments, which were incorporated into the final statement.
Topics: Chronobiology Disorders; Consensus; Evidence-Based Medicine; Humans; London; Parasomnias; Psychopharmacology; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders
PubMed: 31271339
DOI: 10.1177/0269881119855343 -
Open Forum Infectious Diseases Aug 2019Using published data, we sought to compare outcomes in patients transitioned to either oral fluoroquinolones (FQ) or trimethoprim-sulfamethoxazole (TMP-SMX) versus...
BACKGROUND
Using published data, we sought to compare outcomes in patients transitioned to either oral fluoroquinolones (FQ) or trimethoprim-sulfamethoxazole (TMP-SMX) versus ß-lactams (BL's) after an initial intravenous (IV) course for gram-negative rod (GNR) bacteremia.
METHODS
We conducted a systematic review of PubMed and EMBASE and published IDWeek abstracts. We included studies that reported all-cause mortality and/or infection recurrence in patients transitioned to oral FQ/TMP-SMX and BL's.
RESULTS
Eight retrospective studies met inclusion criteria with data for 2,289 patients, of whom 65% were transitioned to oral FQ, 7.7% to TMP-SMX, and 27.2% to BL's. Follow up periods ranged from 21 to 90 days. All-cause mortality was not significantly different between patients transitioned to either FQ/TMP-SMX or BL's (OR 1.13; 95%CI, 0.69-1.87). Overall recurrence of infection, either bacteremia or the primary site, occurred more frequently in patients transitioned to oral BL's vs. FQ's (OR 2.05, 95% CI 1.17 to 3.61). Analysis limited to recurrent bacteremia was similarly suggestive although limited by small numbers (OR 2.32, 95% CI 0.99 to 5.44). However, based on known pharmacokinetics/pharmacodynamics, prescribed ß-lactam dosing regimens were frequently suboptimal.
CONCLUSIONS
In the step-down IV to oral treatment of GNR bacteremia, we found insufficient data regarding outcomes after oral TMP-SMX; however, selection of a FQ over commonly utilized ß-lactam regimens may reduce chances of infection recurrence. While this may be a class effect, it may simply be the result of inadequate dosing of ß-lactams. Additional investigations are warranted to determine outcomes with TMP-SMX and optimized oral ß-lactam dosing regimens.
PubMed: 31412127
DOI: 10.1093/ofid/ofz364 -
The Journal of International Medical... Jun 2020To assess the efficacy of herbal medicine (cinnamon/fennel/ginger) for treating primary dysmenorrhea. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy of herbal medicine (cinnamon/fennel/ginger) for treating primary dysmenorrhea.
METHODS
Relevant studies were searched in multiple databases. The weighted mean difference (WMD) was used as the effect indicator for measurement data, and each effect size was given estimates and 95% confidence intervals (CIs).
RESULTS
Nine studies with 647 patients were selected. Compared with the results in the control group, pain intensity was significantly relieved in the trial group when assessed by the intervention (cinnamon placebo: WMD = 1.815, 95% CI = 1.330-2.301; fennel placebo: WMD = 0.528, 95% CI = 0.119-6.829; ginger placebo: WMD = 2.902, 95% CI = 2.039-3.765), observation period (one cycle: WMD = 2.061, 95% CI = 0.815-3.307; one cycles: WMD = 1.831, 95% CI = 0.973-2.690), and study quality (high quality: WMD = 2.224, 95% CI = 1.488-2.960). Pain duration was significantly shorter in the trial group (cinnamon placebo: WMD = 16.200, 95% CI = 15.271-17.129). No publication bias was observed for either outcome.
CONCLUSIONS
For primary dysmenorrhea, cinnamon/fennel/ginger effectively reduced pain intensity, and cinnamon shortened the duration of pain. Further studies are needed to confirm our results.
Topics: Cinnamomum zeylanicum; Dysmenorrhea; Female; Foeniculum; Zingiber officinale; Herbal Medicine; Humans; Randomized Controlled Trials as Topic
PubMed: 32603204
DOI: 10.1177/0300060520936179 -
MCN. the American Journal of Maternal... 2020
Topics: Adult; Dystocia; Female; Humans; Oxytocics; Oxytocin; Pregnancy
PubMed: 33074919
DOI: 10.1097/NMC.0000000000000659 -
Therapeutic Drug Monitoring Feb 2020Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug...
Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and neuropathy, which are more prevalent with higher exposures and longer treatment durations. Although linezolid is traditionally administered at a standard 600 mg dose every 12 hours, the resulting exposure can vary greatly between patients and can lead to treatment failure or toxicity. The efficacy and toxicity of linezolid are determined by the exposure achieved in the patient; numerous clinical and population pharmacokinetics (popPK) studies have identified threshold measurements for both parameters. Several special populations with an increased need for linezolid dose adjustments have also been identified. Therapeutic Drug Monitoring (TDM) is a clinical strategy that assesses the response of an individual patient and helps adjust the dosing regimen to maximize efficacy while minimizing toxicity. Adaptive feedback control and model-informed precision dosing are additional strategies that use Bayesian algorithms and PK models to predict patient-specific drug exposure. TDM is a very useful tool for patient populations with sparse clinical data or known alterations in pharmacokinetics, including children, patients with renal insufficiency or those receiving renal replacement therapy, and patients taking co-medications known to interact with linezolid. As part of the clinical workflow, clinicians can use TDM with the thresholds summarized from the current literature to improve linezolid dosing for patients and maximize the probability of treatment success.
Topics: Anti-Bacterial Agents; Bayes Theorem; Drug Dosage Calculations; Drug Interactions; Drug Monitoring; Half-Life; Humans; Linezolid; Liver Failure; Metabolic Clearance Rate; Microbial Sensitivity Tests; Models, Biological; Pediatrics; Renal Insufficiency; Renal Replacement Therapy; Tuberculosis
PubMed: 31652190
DOI: 10.1097/FTD.0000000000000710