Explore the vast range of titles available.

Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA ( n  = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39–6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00–3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65–3.77), propantheline (RR = 2.39, 95% C.I. = 1.97–2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88–2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59–3.38), doxepin (RR = 2.30, 95% C.I. = 1.85–2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30–3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67–2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34–3.26), atropine, (RR = 2.03, 95% C.I. = 1.22–3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28–2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n  = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91–2.68), benzamides (RR = 2.23, 95% C.I. = 1.75–3.10), TCAs (RR = 2.23, 95% C.I. = 1.83–2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83–2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes’ co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.

Four vocally untrained healthy adults, 2 men and 2 women, completed the study. A double-blind placebo-controlled approach was used to administer three treatments to each participant on separate days. Drugs treatments involved a single 60-mg dose of a diuretic, Lasix (LA), on one day, and a single 50-mg dose of an oral antihistamine, diphenhydramine hydrochloride (DH), on another day. A third day involved the administration of a placebo, sugar pills (SP). Critical posttreatment measures were weight (kg), which estimated systemic dehydration, saliva viscosity (centipoise), which estimated secretion dehydration, and phona-tion threshold pressure (PTP, in cm H 2 O), at high pitches, which indicated pulmonary drive for phonation. The central experimental question was: Does systemic dehydration, or secretory dehydration, or both, mediate increases in PTP that are known to occur following dehydration treatments? The results showed that LA induced systemic dehydration, as shown by a decrease in total body mass of about 1%. Weight losses were seen during a 1- to 4-hour block following drug administration and persisted for at least 8 hours thereafter. PTPs also increased in that condition, about 23% relative to baseline, but only several hours after whole-body dehydration was initially seen (5–12 hours after drug administration). In contrast, no evidence was seen that DH accomplished either secretory dehydration or PTP shifts. The results indicate that systemic dehydration can mediate PTP increases. The influence of secretory dehydration on PTP is unclear.

Purpose The effects of first-generation antihistamines in preventing postoperative emergence agitation or delirium are unclear. Determining the postoperative effects of first-generation antihistamines may provide important insights into the management of patient safety. Therefore, we performed a systematic review of randomized controlled trials (RCTs) evaluating the efficacy and safety of postoperative first-generation antihistamines. Methods Patients who used first-generation antihistamines in the intensive care unit or operating room were included. Primary outcomes were assessed postoperative emergence agitation or delirium with binary and continuous variables. The secondary outcome was any adverse event. Results Nine studies were included. The frequency of postoperative emergence agitation, measured using binary variables, tended to be lower in patients receiving chlorpheniramine or diphenhydramine than those receiving saline. However, evaluation using the Richmond Agitation-Sedation Scale as a continuous variable revealed that only chlorpheniramine was effective at lowering postoperative emergence agitation. Only one study assessed delirium but found no benefit of first-generation antihistamines. Adverse events for first-generation antihistamines did not differ from that of other drugs. Conclusion Our results provide limited evidence that some first-generation antihistamines may prevent postoperative emergence agitation and are safe. To further verify this possibility, new RCTs with clear and universal assessment criteria for postoperative emergence agitation or delirium should be conducted.

Purpose Cetirizine is a less sedative alternative to diphenhydramine for the prevention of infusion-related reactions (IRR) to paclitaxel. However, its use remains controversial. In this study, we assessed feasibility for a future definitive non-inferiority trial comparing cetirizine to diphenhydramine as premedication to prevent paclitaxel-related IRR. Methods This was a single-center randomized prospective feasibility study. Participants were paclitaxel-naive cancer patients scheduled to start paclitaxel chemotherapy. They were randomly assigned to receive either intravenous diphenhydramine 50 mg + oral placebo (control) or intravenous placebo + oral cetirizine 10 mg (intervention) for their first two paclitaxel treatments. The percentage of eligible patients completing a first paclitaxel treatment and the recruitment rate were assessed (feasibility outcomes). Drowsiness was measured at baseline and at selected time points using the Stanford Sleepiness Scale (SSS) (safety outcome). IRR events were also documented (efficacy outcome). Results Among 37 eligible patients, 27 were recruited and randomized (control 13; intervention 14) and 25 completed the study. The recruitment rate was 4.8 participants/month, meeting the primary feasibility target. Drowsiness was the main adverse effect associated with the premedication. The increase in drowsiness compared to baseline (ΔSSS) was greater in the diphenhydramine group compared to the cetirizine group (median ΔSSS 2 (IQR 3.25) vs median ΔSSS 0 (IQR 1), p  < 0.01) when measured one hour after the premedication administration. One participant had an IRR and no unexpected serious adverse event occurred. Conclusion The trial methods were feasible in terms of recruitment, retention, and safety. Cetirizine was significantly less sedating than diphenhydramine. IRR were infrequent and a larger trial is warranted to confirm non-inferiority for IRR prevention. Trial registration ClinicalTrials.gov, NCT04237090 (22.01.2020).

Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as “Known Risk of TdP” but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the “Known Risk” substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common “Known Risk” substances were citalopram, escitalopram and cocaine. Although not in the “Known Risk” category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2–55.8) and methadone (OR 7.1, 95% CI 2.1–23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of “Known Risk of TdP” QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias.

Background The unintentional misuse of over-the-counter sleep aids among older adults is an important public health problem and a focus of Healthy People 2020. Accordingly, the 2015 Beers Criteria for Potentially Inappropriate Medication Use in Older Adults recommends that individuals 65 years or older avoid use of diphenhydramine and doxylamine; however, many over-the-counter sleep products contain these active ingredients. Objective To identify the proportion of older adults using an over-the-counter medication containing diphenhydramine or doxylamine, and compare their characteristics with older adults using an over-the-counter medication that does not contain these ingredients. Setting Study participants were recruited from the Community Registry of the Pittsburgh Claude D. Pepper Older Americans Independence Center. Method The study sample was taken from a larger survey of 1025 participants on sleep health and over-the-counter sleep medication use conducted from February to April 2015. A subset of 169 participants aged 65 and older reporting taking at least one over-the-counter product to improve sleep within the past 30 days (16.5%) were selected for our analysis on associations between participant characteristics and potentially inappropriate use of over-the-counter sleep medications. Main outcome measure The proportion and characteristics of older adults taking at least one over-the-counter medication containing diphenhydramine or doxylamine. Results Of the 223 over-the-counter sleep medications listed by participants, 115 (52%) contained diphenhydramine or doxylamine. Using the Beers Criteria, we found that more than half of participants (59%) had used a potentially inappropriate over-the-counter medication containing diphenhydramine or doxylamine to improve sleep within the past 30 days. Participants taking at least one diphenhydramine or doxylamine containing medication were less likely to be aware of any safety risks in taking over-the-counter sleep medications than participants not taking these products (38 vs 49%, p  = 0.016). Conclusion A majority of older adults in a limited sample from the United States taking an over-the-counter medication to improve sleep are taking a product containing diphenhydramine or doxylamine, both of which are classified as potentially inappropriate for older adults. Awareness of the safety risks of over-the-counter medications and addressing conditions that impact sleep quality could be facilitated through consultation with pharmacists and other healthcare providers.

ObjectivesTo determine the effectiveness of prophylactic anticholinergic medications in reducing extrapyramidal symptoms in patients taking acute antiemetics with a dopamine D2 receptor antagonist effect.MethodsSystematic searches of all published studies through March 2017 were identified from PubMed, Cochrane library, Embase, Web of Science and Scopus. Only randomised controlled trials of patients receiving dopamine D2 antagonist antiemetic therapy for acute migraine in which an anticholinergic or placebo was compared were included. Pooled ORs were calculated for incidence of extrapyramidal symptoms and sedation.ResultsFour placebo-controlled randomised controlled trials consisting of 737 patients met the inclusion criteria for our meta-analysis. The effect of diphenhydramine differed depending on the method of administration of the antiemetic. When the antiemetic was delivered as a 2 min antiemetic bolus, the odds of extrapyramidal symptoms were significantly reduced in the diphenhydramine group compared with placebo (OR 0.42; 95% CI 0.22 to 0.81; P=0.01). However, when the antiemetic was given as a 15 min infusion, there was no significant difference in extrapyramidal symptoms with or without diphenhydramine (OR 1.06; 95% CI 0.58 to 1.91; P=0.85). The lowest incidence of extrapyramidal symptoms was observed in patients receiving a 15 min antiemetic infusion without diphenhydramine prophylaxis (9.8%). In two trials including 351 patients that dichotomously reported sedation scales, diphenhydramine had significantly higher rates of sedation (31.6%vs19.2%, OR 2.01, 95% CI 1.21 to 3.33; P=0.007).ConclusionProphylactic diphenhydramine reduces extrapyramidal symptoms in patients receiving bolus antiemetic therapy with a dopamine D2 antagonist effect, but not when it is given as an infusion. Because of significantly greater sedation with diphenhydramine, the most effective strategy is to administer the D2 antagonist antiemetic as a 15 min infusion without prophylaxis.

The antihistaminic drug diphenhydramine (DPH) is mainly used as a sedative, hypnotic and antiemetic. In many countries it is over-the-counter available, very common, and generally regarded as a harmless drug. Sixty-eight non-fatal and 55 fatal poisonings with DPH alone or in combination with other drugs were investigated in the Institute of Legal Medicine of the University Hospital Charité between 1992 and 2004. The analytical investigations were performed by HPLC with photodiode array detector (HPLC-DAD). The DPH concentrations ranged from 0.5 to 8.9 μg/mL in the non-fatal cases and from 0.3 to 119 μg/mL in fatal cases. The intoxication symptoms stated during emergency admission were inconsistent, with somnolence, sedation and retardation on one hand and tachycardia, anticholinergic syndrome, agitation, hallucinations, confusion, tremor, convulsions, delirium and coma on the other. In three cases rhabdomyolysis occurred. A concentration above 5 μg/mL can be regarded as potentially lethal. In many of the survivors the time course of the concentrations of DPH and the metabolites desmethyldiphenhydramine (DM-DPH) and diphenylmethoxyacetic acid (DPMA) were investigated. Whereas DM-DPH is present in blood from the very beginning because of the high first pass metabolism, DPMA is slowly formed over several metabolic steps. For this reason, the concentration ratio DPMA/DPH can be used for an approximate estimation of the time between drug intake and sampling in clinical cases or of the survival time after drug ingestion in death cases. In some of the deaths the concentrations in heart blood were much higher than in venous blood. This is explained mainly by agonal aspiration of the vomited gastric content. Besides the majority of suicidal cases also a case of child maltreatment and a case, in which the drug was forcibly administrated in a drug facilitated crime, were investigated. From the results it follows that diphenhydramine is not less poisonous than other prescribed hypnotics. However, despite the hallucinogenic effects, an abuse for recreational purposes was not observed until now.

Causative agents may be mechanical (size, location, composition of intravenous cannula), chemical (drugs, infusates) or biological (infections). Old age, thin body habitus and atopic tendency have also been thought to increase incidence and severity.5 Transient phlebitis has been described after intravenous administration of several drugs (meperidine, morphine, rocuronium, propofol, eptifibatide and ciprofloxacin).5–10 Hypothesised mechanisms associated with this phenomenon include tissue damage, local mediator release, histamine release, direct activation of C-nociceptors and activation of kallikrein-kinin system with bradykinin generation.5 6 Diphenhydramine is an antihistamine (H-1 receptor antagonist) with anticholinergic and sedative effects. Infusion phlebitis assessment measures: a systematic review.