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Progress in Neuro-psychopharmacology &... Jun 2024The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic... (Review)
Review
BACKGROUND
The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD.
METHODS
PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected.
RESULTS
Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1β, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients.
CONCLUSION
Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.
PubMed: 38879067
DOI: 10.1016/j.pnpbp.2024.111056 -
European Journal of Clinical... Jun 2024Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of... (Review)
Review
OBJECTIVES
Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of linezolid are often overlooked. This manuscript aims to review the medications that affect the pharmacokinetics of linezolid.
METHODS
In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the PubMed, Embase, and Cochrane Library for publications from database establishment to November 3, 2023, using the search terms: "Linezolid" and "interaction," or "interact," or "drug-drug interaction," or "co-treatment," or "cotreatment," or "combined," or "combination."
RESULTS
A total of 24 articles were included. Among the reported medication interactions, rifampicin, levothyroxine, venlafaxine, and phenobarbital could reduce the concentration of linezolid; clarithromycin, digoxin, cyclosporine, proton pump inhibitors, and amiodarone could increase the concentration of linezolid, while aztreonam, phenylpropanolamine, dextromethorphan, antioxidant vitamins, and magnesium-containing antacids had no significant effects on linezolid pharmacokinetics. The ratio of mean (ROM) of linezolid AUC in co-treatment with rifampicin to monotherapy was 0.67 (95%CI 0.58-0.77) and 0.63 (95%CI 0.43-0.91), respectively, in 2 studies, and co-treatment with 500 mg clarithromycin to monotherapy was 1.81 (95%CI 1.49-2.13).
CONCLUSIONS
This systematic review found that numerous drugs have an impact on the pharmacokinetics of linezolid, and the purported main mechanism may be that linezolid is the substrate of P-glycoprotein. In clinical practice, it is prudent to pay attention to the changes in linezolid pharmacokinetics caused by interactions. Conducting therapeutic drug monitoring (TDM) is beneficial to improve efficacy and reduce adverse reactions of linezolid.
Topics: Drug Interactions; Linezolid; Humans; Anti-Bacterial Agents
PubMed: 38421436
DOI: 10.1007/s00228-024-03652-2 -
JMIR Public Health and Surveillance Jan 2024Drug-induced suicide (DIS) is a severe adverse drug reaction (ADR). Although clinical trials have provided evidence on DIS, limited investigations have been performed on... (Review)
Review
BACKGROUND
Drug-induced suicide (DIS) is a severe adverse drug reaction (ADR). Although clinical trials have provided evidence on DIS, limited investigations have been performed on rare ADRs, such as suicide.
OBJECTIVE
We aimed to systematically review case reports on DIS to provide evidence-based drug information.
METHODS
We searched PubMed to obtain case reports regarding DIS published until July 2021. Cases resulting from drugs that are no longer used or are nonapproved, substance use, and suicidal intentions were excluded. The quality of each case report was assessed using the CASE (Case Reports) checklist. We extracted data regarding demographics, medication history, suicide symptoms, and symptom improvement and evaluated the causality of DIS using the Naranjo score. Furthermore, to identify the potential suicidal risk of the unknown drugs, we compared the results of the causality assessment with those of the approved drug labels.
RESULTS
In 83 articles, we identified 152 cases involving 61 drugs. Antidepressants were reported as the most frequent causative drugs of DIS followed by immunostimulants. The causality assessment revealed 61 cases having possible, 89 cases having probable, and 2 cases having definite relationships with DIS. For approximately 85% of suspected drugs, the risk of suicidal ADRs was indicated on the approved label; however, the approved labels for 9 drugs, including lumacaftor/ivacaftor, doxycycline, clozapine, dextromethorphan, adalimumab, infliximab, piroxicam, paclitaxel, and formoterol, did not provide information about these risks.
CONCLUSIONS
We found several case reports involving drugs without suicide risk information on the drug label. Our findings might provide valuable insights into drugs that may cause suicidal ADRs.
Topics: Humans; Doxycycline; Drug Labeling; Drug-Related Side Effects and Adverse Reactions; Suicidal Ideation; Suicide; Case Reports as Topic
PubMed: 38289650
DOI: 10.2196/49755 -
Biomedicines Sep 2023This umbrella review aimed to determine the various drugs used to treat trigeminal neuralgia (TN) and to evaluate their efficacies as well as side effects by surveying... (Review)
Review
This umbrella review aimed to determine the various drugs used to treat trigeminal neuralgia (TN) and to evaluate their efficacies as well as side effects by surveying previously published reviews. An online search was conducted using PubMed, CRD, EBSCO, Web of Science, Scopus, and the Cochrane Library with no limits on publication date or patients' gender, age, and ethnicity. Reviews and meta-analyses of randomized controlled trials pertaining to drug therapy for TN, and other relevant review articles added from their reference lists, were evaluated. Rapid reviews, reviews published in languages other than English, and reviews of laboratory studies, case reports, and series were excluded. A total of 588 articles were initially collected; 127 full-text articles were evaluated after removing the duplicates and screening the titles and abstracts, and 11 articles were finally included in this study. Except for carbamazepine, most of the drugs had been inadequately studied. Carbamazepine and oxcarbazepine continue to be the first choice for medication for classical TN. Lamotrigine and baclofen can be regarded as second-line drugs to treat patients not responding to first-line medication or for patients having intolerable side effects from carbamazepine. Drug combinations using carbamazepine, baclofen, gabapentin, ropivacaine, tizanidine, and pimozide can yield satisfactory results and improve the tolerance to the treatment. Intravenous lidocaine can be used to treat acute exaggerations and botulinum toxin-A can be used in refractory cases. Proparacaine, dextromethorphan, and tocainide were reported to be inappropriate for treating TN. Anticonvulsants are successful in managing trigeminal neuralgia; nevertheless, there have been few studies with high levels of proof, making it challenging to compare or even combine their results in a statistically useful way. New research on other drugs, combination therapies, and newer formulations, such as vixotrigine, is awaited. There is conclusive evidence for the efficacy of pharmacological drugs in the treatment of TN.
PubMed: 37892981
DOI: 10.3390/biomedicines11102606 -
CNS Drugs Oct 2023A significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as...
BACKGROUND
A significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as first-generation monoamine-based antidepressants.
OBJECTIVES
The objective of this systematic review was to assess the efficacy, safety, and mechanisms of action of AXS-05, a combination of the NMDA-receptor antagonist dextromethorphan with bupropion, in adults with MDD.
METHODS
We searched PubMed, Embase, Google Scholar, and ClinicalTrials.gov for current studies reporting on efficacy and/or safety of AXS-05 in patients with MDD. The search terms included: "AXS-05" OR "dextromethorphan and bupropion" AND "depression". Studies from database inception to January 2023 were evaluated. Risk of bias was assessed using the Cochrane Risk of Bias tool.
RESULTS
The search yielded 54 studies of which 5 were included. All studies had low risk of bias. Depression severity, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) significantly decreased as early as 1-week post-treatment from baseline when compared to a placebo-controlled group (LS mean difference 2.2; 95% CI 0.6-3.9; p = 0.007) and at 2 weeks compared to an active control group (LS mean difference 4.7; 95% CI 0.6-8.8; p = 0.024). Treatment efficacy could be maintained for up to 12 months with mean MADRS score reduction of 23 points from baseline. Clinical remission and response rates also improved at week 1 and were maintained for 12 months. The treatment was well-tolerated, with some transient adverse events reported.
CONCLUSION
Current evidence suggests that the combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment option for adults with MDD. Initial success with AXS-05 supports the mechanistic role of glutamatergeric and sigma 1 signaling in the pathophysiology of MDD.
Topics: Adult; Humans; Antidepressive Agents; Bupropion; Depression; Depressive Disorder, Major; Dextromethorphan; Clinical Trials as Topic
PubMed: 37792265
DOI: 10.1007/s40263-023-01032-5 -
Brain Injury Jul 2022To review the role of N-methyl-D-aspartate receptor (NMDAR) antagonists in managing post-TBI cognitive deficits.
OBJECTIVE
To review the role of N-methyl-D-aspartate receptor (NMDAR) antagonists in managing post-TBI cognitive deficits.
METHODS
A search of PubMed, Embase, and Cochrane was conducted on Jan 12, 2021 without publication date or language restriction.
RESULTS
Forty-seven studies were included, involving 20 (42.6%) randomized controlled trials. Four (8.5%) studies had a low risk of bias (RoB), while 34 (72.3%) had unclear and nine (19.2%) had high RoB. Six NMDAR antagonists had been investigated: amantadine (n = 32), memantine (n = 4), magnesium (n = 4), traxoprodil (n = 3), selfotel (n = 2), and dextromethorphan (n = 2).
CONCLUSION
Although some benefits were observed, there are still some concerns regarding the efficacy and safety of NMDAR antagonists in improving post-TBI cognitive deficits. Further research is required to examine whether (i) these agents, notably amantadine, could accelerate cognitive improvement and shorten the hospital stay, (ii) these agents affect different cognitive domains/subdomains in the same direction, (iii) an optimal therapeutic time window exists, (iv) a member of this drug class can be proved to be effective without interfering in non-excitotoxic actions of glutamate, (v) they can be more effective as part of combination therapies or in particular subgroups of patients with TBI.
Topics: Brain Injuries, Traumatic; Cognition; Cognition Disorders; Humans; Memantine; Receptors, N-Methyl-D-Aspartate
PubMed: 35997315
DOI: 10.1080/02699052.2022.2109749 -
Frontiers in Pharmacology 2022Many investigational drugs with antidepressant activity are currently explored in different phases of clinical research, with indications such as major depressive...
Many investigational drugs with antidepressant activity are currently explored in different phases of clinical research, with indications such as major depressive disorder, treatment-resistant major depression, bipolar depression, post-partum depression, and late-life depression. Although the vast majority of the antidepressants in clinical use are based on the monoaminergic hypothesis of depression, recent data supported the launching on the market of two new, non-monoamine-modulating drugs. Esketamine for treatment-resistant major depression and brexanolone for post-partum depression are two exceptions from the monoaminergic model, although their use is still limited by high costs, unique way of administration (only intravenously for brexanolone), physicians' reluctance to prescribe new drugs, and patients' reticence to use them. Glutamatergic neurotransmission is explored based on the positive results obtained by intranasal esketamine, with subanesthetic intravenous doses of ketamine, and D-cycloserine, traxoprodil, MK-0657, AXS-05, AVP-786, combinations of cycloserine and lurasidone, or dextromethorphan and quinidine, explored as therapeutic options for mono- or bipolar depression. Sestrin modulators, cholinergic receptor modulators, or onabotulinumtoxinA have also been investigated for potential antidepressant activity. In conclusion, there is hope for new treatments in uni- and bipolar depression, as it became clear, after almost 7 decades of monoamine-modulating antidepressants, that new pathogenetic pathways should be targeted to increase the response rate in this population.
PubMed: 35847011
DOI: 10.3389/fphar.2022.884155 -
World Journal of Otorhinolaryngology -... Jun 2022Management of postoperative pain after head and neck cancer surgery is a complex issue, requiring a careful balance of analgesic properties and side effects. The... (Review)
Review
OBJECTIVE
Management of postoperative pain after head and neck cancer surgery is a complex issue, requiring a careful balance of analgesic properties and side effects. The objective of this review is to discuss the efficacy and safety of multimodal analgesia (MMA) for these patients.
METHODS
Pubmed, Cochrane, Embase, Scopus, and clinicaltrials.gov were systematically searched for all comparative studies of patients receiving MMA (nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, anticonvulsants, local anesthetics, and corticosteroids) for head and neck cancer surgeries. The primary outcome was additional postoperative opioid usage, and secondary outcomes included subjective pain scores, complications, adverse effects, and 30-day outcomes.
RESULTS
A total of five studies representing 592 patients (MMA, = 275; non-MMA, = 317) met inclusion criteria. The most commonly used agents were gabapentin, NSAIDs, and acetaminophen ( = 221), NSAIDs ( = 221), followed by corticosteroids ( = 35), dextromethorphan ( = 40), and local nerve block ( = 19). Four studies described a significant decrease in overall postoperative narcotic usage with two studies reporting a significant decrease in hospital time. Subjective pain scores widely varied with two studies reporting reduced pain at postoperative day 3. There were no differences in surgical outcomes, medical complications, adverse effects, or 30-day mortality and readmission rates.
CONCLUSION
MMA is an increasingly popular strategy that may reduce dependence on opioids for the treatment of postoperative pain. A variety of regimens and protocols are available for providers to utilize in the appropriate head and neck cancer patient.
PubMed: 35782401
DOI: 10.1002/wjo2.62 -
The Cochrane Database of Systematic... May 2022Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative condition that may cause dysphagia, as well as limb... (Review)
Review
BACKGROUND
Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative condition that may cause dysphagia, as well as limb weakness, dysarthria, emotional lability, and respiratory failure. Since normal salivary production is 0.5 L to 1.5 L daily, loss of salivary clearance due to dysphagia leads to salivary pooling and sialorrhea, often resulting in distress and inconvenience to people with MND. This is an update of a review first published in 2011.
OBJECTIVES
To assess the effects of treatments for sialorrhea in MND, including medications, radiotherapy and surgery.
SEARCH METHODS
On 27 August 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, ClinicalTrials.gov and the WHO ICTRP. We checked the bibliographies of the identified randomized trials and contacted trial authors as needed. We contacted known experts in the field to identify further published and unpublished papers.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-RCTs, including cross-over trials, on any intervention for sialorrhea and related symptoms, compared with each other, placebo or no intervention, in people with ALS/MND.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified four RCTs involving 110 participants with MND who were described as having intractable sialorrhea or bulbar dysfunction. A well-designed study of botulinum toxin B compared to placebo injected into the parotid and submandibular glands of 20 participants showed that botulinum toxin B may produce participant-reported improvement in sialorrhea, but the confidence interval (CI) was also consistent with no effect. Six of nine participants in the botulinum group and two of nine participants in the placebo group reported improvement (risk ratio (RR) 3.00, 95% CI 0.81 to 11.08; 1 RCT; 18 participants; low-certainty evidence). An objective measure indicated that botulinum toxin B probably reduced saliva production (in mL/5 min) at eight weeks compared to placebo (MD -0.50, 95% CI -1.07 to 0.07; 18 participants, moderate-certainty evidence). Botulinum toxin B may have little to no effect on quality of life, measured on the Schedule for Evaluation of Individual Quality of Life direct weighting scale (SEIQoL-DW; 0-100, higher values indicate better quality of life) (MD -2.50, 95% CI -17.34 to 12.34; 1 RCT; 17 participants; low-certainty evidence). The rate of adverse events may be similar with botulinum toxin B and placebo (20 participants; low-certainty evidence). Trialists did not consider any serious events to be related to treatment. A randomized pilot study of botulinum toxin A or radiotherapy in 20 participants, which was at high risk of bias, provided very low-certainty evidence on the primary outcome of the Drool Rating Scale (DRS; range 8 to 39 points, higher scores indicate worse drooling) at 12 weeks (effect size -4.8, 95% CI -10.59 to 0.92; P = 0.09; 1 RCT; 16 participants). Quality of life was not measured. Evidence for adverse events, measured immediately after treatment (RR 7.00, 95% CI 1.04 to 46.95; 20 participants), and after four weeks (when two people in each group had viscous saliva) was also very uncertain. A phase 2, randomized, placebo-controlled cross-over study of 20 mg dextromethorphan hydrobromide and 10 mg quinidine sulfate (DMQ) found that DMQ may produce a participant-reported improvement in sialorrhea, indicated by a slight improvement (decrease) in mean scores for the primary outcome, the Center for Neurologic Study Bulbar Function Scale (CNS-BFS). Mean total CNS-BFS (range 21 (no symptoms) to 112 (maximum symptoms)) was 53.45 (standard error (SE) 1.07) for the DMQ treatment period and 59.31 (SE 1.10) for the placebo period (mean difference) MD -5.85, 95% CI -8.77 to -2.93) with a slight decrease in the CNS-BFS sialorrhea subscale score (range 7 (no symptoms) to 35 (maximum symptoms)) compared to placebo (MD -1.52, 95% CI -2.52 to -0.52) (1 RCT; 60 participants; moderate-certainty evidence). The trial did not report an objective measure of saliva production or measure quality of life. The study was at an unclear risk of bias. Adverse events were similar to other trials of DMQ, and may occur at a similar rate as placebo (moderate-certainty evidence, 60 participants), with the most common side effects being constipation, diarrhea, nausea, and dizziness. Nausea and diarrhea on DMQ treatment resulted in one withdrawal. A randomized, double-blind, placebo-controlled cross-over study of scopolamine (hyoscine), administered using a skin patch, involved 10 randomized participants, of whom eight provided efficacy data. The participants were unrepresentative of clinic cohorts under routine clinical care as they had feeding tubes and tracheostomy ventilation, and the study was at high risk of bias. The trial provided very low-certainty evidence on sialorrhea in the short term (7 days' treatment, measured on the Amyotrophic Lateral Scelerosis Functional Rating Scale-Revised (ALSFRS-R) saliva item (P = 0.572)), and the amount of saliva production in the short term, as indicated by the weight of a cotton roll (P = 0.674), or daily oral suction volume (P = 0.69). Quality of life was not measured. Adverse events evidence was also very uncertain. One person treated with scopolamine had a dry mouth and one died of aspiration pneumonia considered unrelated to treatment.
AUTHORS' CONCLUSIONS
There is some low-certainty or moderate-certainty evidence for the use of botulinum toxin B injections to salivary glands and moderate-certainty evidence for the use of oral dextromethorphan with quinidine (DMQ) for the treatment of sialorrhea in MND. Evidence on radiotherapy versus botulinum toxin A injections, and scopolamine patches is too uncertain for any conclusions to be drawn. Further research is required on treatments for sialorrhea. Data are needed on the problem of sialorrhea in MND and its measurement, both by participant self-report measures and objective tests. These will allow the development of better RCTs.
Topics: Amyotrophic Lateral Sclerosis; Botulinum Toxins, Type A; Clinical Trials, Phase II as Topic; Deglutition Disorders; Diarrhea; Humans; Motor Neuron Disease; Nausea; Randomized Controlled Trials as Topic; Saliva; Scopolamine Derivatives; Sialorrhea
PubMed: 35593746
DOI: 10.1002/14651858.CD006981.pub3 -
Pharmacogenomics Mar 2022Pharmacogenomics (PGx) is a rising scientific area in many countries, such as Brazil. To identify biomarkers, therapeutic areas, probe drugs and regions/ethnicities... (Review)
Review
Pharmacogenomics (PGx) is a rising scientific area in many countries, such as Brazil. To identify biomarkers, therapeutic areas, probe drugs and regions/ethnicities most studied in the country in order to guide future studies. Systematic review of 1060 studies (from 1968 to 2020) comprising 80 genes, six probe drugs and 3,819,233 individuals. and were the most studied genes and metoprolol and dextromethorphan the most studied probe drugs. Oncology was the most studied therapeutic area considering PGx biomarkers. The country's regions and ethnic groups were studied unevenly, with south/southeast and White people over-represented in respect to their demographic relevance, in detriment of the center-west/northeast/north and Black/mixed individuals. Many of the gaps and possible paths to be covered to reach even PGx data are pointed out by this review.
Topics: Brazil; Ethnicity; HLA-B Antigens; Humans; Medical Oncology; Pharmacogenetics
PubMed: 35187980
DOI: 10.2217/pgs-2021-0128