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Handbook of Clinical Neurology 2021Histamine in the brain is produced by a group of tuberomamillary neurons in the posterior hypothalamus and a limited number of mast cells in different parts of the... (Review)
Review
Histamine in the brain is produced by a group of tuberomamillary neurons in the posterior hypothalamus and a limited number of mast cells in different parts of the brain. Four G-protein-coupled receptors mediate the effects of histamine. Two of these receptors, H3 and H4 receptors, are high-affinity receptors in the brain and immune system, respectively. The two classic histamine receptors, H1 receptor and H2 receptor, are well known as drug targets for allergy and gastric ulcer, respectively. These receptors have lower affinity for histamine than the more recently discovered H3 and H4 receptors. The H1 and H2 receptors are important postsynaptic receptors in the brain, and they mediate many of the central effects of histamine on, e.g., alertness and wakefulness. H3 receptor is a pre- and postsynaptic receptor, which regulates release of histamine and several other neurotransmitters, including serotonin, GABA, and glutamate. H4 receptor is found in cerebral blood vessels and microglia, but its expression in neurons is not yet well established. Pitolisant, a H3 receptor antagonist, is used to treat narcolepsy and hypersomnia. H1 receptor antagonists have been used to treat insomnia, but its use requires precautions due to potential side effects. H2 receptor antagonists have shown efficacy in treatment of schizophrenia, but they are not in widespread clinical use. H4 receptor ligands may in the future be tested for neuroimmunological disorders and potentially neurodegenerative disorders in which inflammation plays a role, but clinical tests have not yet been initiated.
Topics: Brain; Histamine; Humans; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H3
PubMed: 34225942
DOI: 10.1016/B978-0-12-820107-7.00023-9 -
JAMA Psychiatry Oct 2022Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown.
Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial.
IMPORTANCE
Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown.
OBJECTIVE
To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy.
DESIGN, SETTING, AND PARTICIPANTS
In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD.
INTERVENTIONS
Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy.
MAIN OUTCOMES AND MEASURES
The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance.
RESULTS
A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin.
CONCLUSIONS AND RELEVANCE
Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02061293.
Topics: Adult; Alcohol Drinking; Alcoholism; Diphenhydramine; Double-Blind Method; Female; Hallucinogens; Humans; Male; Middle Aged; Psilocybin; Psychotherapy; Treatment Outcome
PubMed: 36001306
DOI: 10.1001/jamapsychiatry.2022.2096 -
Clinical Reviews in Allergy & Immunology Jun 2022Hypersensitivity reactions (HSRs) to chemotherapy may prevent patients from receiving the most effective therapy. This review was undertaken to identify evidence-based... (Review)
Review
Hypersensitivity reactions (HSRs) to chemotherapy may prevent patients from receiving the most effective therapy. This review was undertaken to identify evidence-based preventive premedication strategies that reduce the likelihood of HSR in the first instance and improve the safety of subsequent infusions in patients who have demonstrated HSR to a certain class of chemotherapy. PubMed was searched until October 2021 using the key words: "hypersensitivity to chemotherapeutic drugs," "hypersensitivity to antineoplastic agents," "taxanes hypersensitivity," "platinum compound hypersensitivity," "premedication," "dexamethasone," "prednisone," "hydrocortisone," "antihistamine," "diphenhydramine," "cetirizine," "famotidine," "meperidine," "aspirin," "ibuprofen," and "montelukast." The search was restricted to articles published in English. A total of 73 abstracts were selected for inclusion in the review. Most premedication regimens have been derived empirically rather than determined through randomized trials. Based on the available evidence, we provide an update on likely HSR mechanisms and a practical guide for classifying systemic HSR. The evidence indicates that a combination of prevention strategies using newer antihistamines, H2 antagonists, leukotriene receptor antagonists, and corticosteroids and other interventions used judiciously reduces the occurrence and severity of HSR and improves safety.
Topics: Drug Hypersensitivity; Histamine Antagonists; Humans; Paclitaxel; Premedication; Taxoids
PubMed: 35258842
DOI: 10.1007/s12016-022-08932-2 -
The Medical Letter on Drugs and... Jan 2023
Topics: Humans; Sleep Initiation and Maintenance Disorders; Hypnotics and Sedatives
PubMed: 36630579
DOI: 10.58347/tml.2023.1667a -
Human Psychopharmacology Mar 2023The purpose of this systematic review is to assess the efficacy and safety of hydroxyzine for insomnia in adults. (Review)
Review
OBJECTIVE
The purpose of this systematic review is to assess the efficacy and safety of hydroxyzine for insomnia in adults.
METHODS
A comprehensive literature search of PubMed, Embase, and CENTRAL databases was conducted to identify relevant published studies through October 2022 using the search terms: hydroxyzine and sleep, insomnia, sleep disorder or sleep initiation and maintenance disorders. Studies identified for review included prospective, interventional designs or cohort trials that reported impact of hydroxyzine on sleep in adults. Animal studies, case reports, non-English articles, letters to the editor, case studies, and conference abstracts were excluded. Data were extracted using a standardized systematic process.
RESULTS
Five articles were identified for inclusion, including 1 open-label and 4 randomized controlled trials, evaluating a total of 207 patients receiving hydroxyzine 25 mg, 50 mg, or 100 mg at bedtime. Mixed efficacy was demonstrated in the sleep measures of sleep onset, sleep maintenance, and sleep quality. The most common adverse drug effect was dry mouth, although 4 of the 5 studies did not report safety outcomes.
CONCLUSIONS
The studies in this review suggest hydroxyzine could be considered as a short-term treatment option for adults with insomnia for whom previous therapy was ineffective, not tolerated, or contraindicated. Additional long-term studies with an active comparator are needed to further establish its role in insomnia treatment.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Hypnotics and Sedatives; Hydroxyzine; Prospective Studies; Sleep
PubMed: 36843057
DOI: 10.1002/hup.2864 -
Current Drug Metabolism 2021Adrenergic β-blockers are used to treat many conditions, including hypertension, cardiac arrhythmias, heart failure, angina pectoris, migraine, and tremors. The... (Review)
Review
Adrenergic β-blockers are used to treat many conditions, including hypertension, cardiac arrhythmias, heart failure, angina pectoris, migraine, and tremors. The majority of the β-blockers including Propranolol, Metoprolol, Acebutolol, Alprenolol, Betaxolol, Carvedilol, Nebivolol and Oxprenolol are metabolised majorly by CYP2D6, and Bisoprolol is primarily metabolised by CYP3A4 enzymes. The drugs inhibiting or inducing them may alter the pharmacokinetics of those β-blockers. The plasma concentrations of Propranolol might be elevated by the concomitant use of drugs, such as SSRIs (Fluoxetine, Paroxetine), SNRIs (Duloxetine) and Cimetidine, while the plasma concentrations of Metoprolol increased by the concurrent use of SSRIs (Fluoxetine, Paroxetine), Amiodarone, Celecoxib, Cimetidine, Terbinafine, and Diphenhydramine. β-blockers can also interact pharmacodynamically with drugs, including fluoroquinolones, antidiabetic agents and NSAIDs. In addition, β-blockers may interact with herbs, such as curcumin, Ginkgo biloba, Schisandra chinensis, green tea, guggul, hawthorn, St. John's wort and Yohimbine. This article focuses on clinically relevant drug interactions of β-blockers with commonly prescribed medications. In addition to Pharmacokinetics and Pharmacodynamics of the drug interactions, recommendations for clinical practice are highlighted. The prescribers and the pharmacists are needed to be aware of the drugs interacting with β-blockers to prevent possible adverse drug interactions.
Topics: Adrenergic beta-Antagonists; Drug Interactions; Humans; Medication Therapy Management; Pharmaceutical Preparations
PubMed: 34182907
DOI: 10.2174/1389200222666210614112529 -
Pediatrics Apr 2020Several antiemetics have been used in children with acute gastroenteritis. However, there is still controversy over their use. (Meta-Analysis)
Meta-Analysis
CONTEXT
Several antiemetics have been used in children with acute gastroenteritis. However, there is still controversy over their use.
OBJECTIVE
To determine the effectiveness and safety of antiemetics for controlling vomiting in children with acute gastroenteritis.
DATA SOURCES
Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Latin America and the Caribbean Literature on Health Sciences, and gray literature, until December 2018.
STUDY SELECTION
We selected randomized clinical trials comparing metoclopramide, ondansetron, domperidone, dexamethasone, dimenhydrinate, and granisetron.
DATA EXTRACTION
Two reviewers independently screened abstracts and full texts, extracted the data, and assessed the risk of bias. We performed pairwise and network meta-analysis using the random-effects model.
RESULTS
Twenty-four studies were included (3482 children). Ondansetron revealed the largest effect in comparison to placebo for cessation of vomiting (odds ratio = 0.28 [95% credible interval = 0.16 to 0.46]; quality of evidence: high) and for hospitalization (odds ratio = 2.93 [95% credible interval = 1.69 to 6.18]; quality of evidence: moderate). Ondansetron was the only intervention that reduced the need for intravenous rehydration and the number of vomiting episodes. When considering side effects, dimenhydrinate was the only intervention that was worse than placebo.
LIMITATIONS
Most treatment comparisons had low- or very low-quality evidence, because of risk of biases and imprecise estimates.
CONCLUSIONS
Ondansetron is the only intervention that revealed an effect on the cessation of vomiting, on preventing hospitalizations, and in reducing the need for intravenous rehydration. Ondansetron was also considered a safe intervention.
Topics: Acute Disease; Antiemetics; Child; Child, Preschool; Dexamethasone; Diarrhea; Dimenhydrinate; Domperidone; Fluid Therapy; Gastroenteritis; Granisetron; Hospitalization; Humans; Infant; Metoclopramide; Network Meta-Analysis; Ondansetron; Randomized Controlled Trials as Topic; Regression Analysis; Vomiting
PubMed: 32132152
DOI: 10.1542/peds.2019-3260 -
The Medical Letter on Drugs and... Apr 2021
Topics: Anti-Allergic Agents; Conjunctivitis, Allergic; Glucocorticoids; Histamine H1 Antagonists; Humans; Immunotherapy; Leukotriene Antagonists; Rhinitis, Allergic
PubMed: 33848281
DOI: No ID Found