Triazolam for Pediatric Dental Sedation: A Retrospective Evaluation of Safety and Changes in Visit Behavior.

Purpose: To describe triazolam in pediatric dental mild to moderate sedation and report changes to overall visit behavior for permanent first molar extraction. Methods: This retrospective chart review from 2018 to 2022 analyzed demographic, procedural, and behavioral data for children eight years and older receiving triazolam for a permanent first molar extraction. The outcomes included adverse events measured by deviations in heart rate and oxygen saturation and changes to overall visit-level Frankl scores from the referral to sedation visit. Descriptive statistics and non-parametric statistical analyses were conducted. Results: The study population (n equals 82) was predominantly female (61 percent), English-speaking (85 percent), and White (41 percent) or Black (39 percent). The most common indication for mild to moderate sedation was dental anxiety (28 percent). There were zero instances of adverse events requiring emergency intervention or the use of reversal medication. The change in visit-level Frankl scores was significantly positive (P<0.001). Conclusion: Triazolam is likely a safe choice for mild to moderate sedation, leading to improved overall visit behavior in children undergoing a permanent first molar extraction.

The risk of fractures, acute myocardial infarction, atrial fibrillation and ventricular arrhythmia in geriatric patients exposed to promethazine.

Objectives: This study aimed to compare the risk of fractures, acute myocardial infarction, atrial fibrillation, and ventricular arrhythmia among Danish citizens aged ≥ 65 which were new users of promethazine or domperidone, triazolam, loratadine, and betahistine. Secondly, the study aimed to perform a risk stratification to identify the most relevant predictors for the study outcomes.Methods: The study period was 01/01/2015 to 31/12/2016. The data sources were the Danish registers. Each patient was followed for 90 days. A logistic regression model was used to compute the unadjusted and adjusted odds ratios (OR), and a conditional inference tree was used to identify the most relevant predictors for the study outcomes.Results: Promethazine had a higher risk of hospitalization for atrial fibrillation than loratadine and betahistine (OR 1.58; 95% CI 1.07-2.63 and OR 3.22; 95% CI 1.69-7.14, respectively). For fractures, acute myocardial infarction, and ventricular arrhythmia hospitalizations, no statistically significant differences were found among drugs under investigation. The medical history of cardiac arrhythmia (OR 4.14; 95% CI 2.94-5.78, p < 0.0001) was the most relevant predictor for atrial fibrillation hospitalizations.Conclusion: This study found an increased risk of atrial fibrillation hospitalization among promethazine users, and the risk was higher among patients with prior cardiac arrhythmia.

Segmental Hair Testing of Triazolam to Unmask a Suspected Case of Idiopathic Recurrent Stupor.

ABSTRACT: Stupor is a diagnostic challenge at emergency department. Differential diagnosis includes idiopathic recurrent stupor, formerly attributed to "endozepine-4" accumulation. This condition has been recently questioned because many suspected cases resulted in exogenous benzodiazepine intake that eludes the conventional toxicological assay. In case of unexplained recurrent stupor, to extend the benzodiazepine search in nonconventional matrices can allow unmasking of hidden toxic behavior.

Proposed Guideline Revisions for Dental Sedation and General Anesthesia: Why Target the Safest Level of Sedation?

Recently proposed revisions to the American Dental Association's Guidelines for the Use of Sedation and General Anesthesia by Dentists, aimed at improving safety in dental offices, differentiate between levels of sedation based on drug-induced changes in physiologic and behavioral states. However, the author of this op-ed is concerned the proposed revisions may have far-reaching and unintended consequences.

Next-day residual effects of gabapentin, diphenhydramine, and triazolam on simulated driving performance in healthy volunteers: a phase 3, randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: Next-day residual effects of a nighttime dose of gabapentin 250 mg were evaluated on simulated driving performance in healthy participants in a randomized, placebo-controlled, double-blind, multicenter, four-period crossover study that included diphenhydramine citrate 76 mg and triazolam 0.5 mg. METHODS: At treatment visits, participants (n = 59) were dosed at ~23:30, went to bed immediately, and awakened 6.5 h postdose for evaluation. The primary endpoint was the standard deviation of lateral position for the 100-km driving scenario. Additional measures of driving, sleepiness, and cognition were included. RESULTS: Study sensitivity was established with triazolam, which demonstrated significant next-day impairment on all driving endpoints, relative to placebo (p < 0.001). Gabapentin demonstrated noninferiority to placebo on standard deviation of lateral position and speed deviation but not for lane excursions. Diphenhydramine citrate demonstrated significant impairment relative to gabapentin and placebo on speed deviation (p < 0.05). Other comparisons were either nonsignificant or statistically ineligible per planned, sequential comparisons. Secondary endpoints for sleepiness and cognitive performance were supportive of these conclusions. CONCLUSIONS: Together, these data suggest that low-dose gabapentin had no appreciable next-day effects on simulated driving performance or cognitive functioning. Copyright © 2016 John Wiley & Sons, Ltd.

Quantification of adverse effects of regular use of triazolam on clinical outcomes for older people with insomnia: a retrospective cohort study.

OBJECTIVE: Older people are more likely to have insomnia. One of the most prescribed hypnotics in Japan is triazolam. Although some studies showed the possibility of adverse effects of triazolam in older people, there have been few studies investigating these effects in a clinical setting. The aim of this study was to determine whether patients who used triazolam regularly had increased risks of pneumonia, trauma, and pressure ulcers. METHODS: The research design was a retrospective cohort study using claim data. The subjects of the study were patients who were insured by Fukuoka Late Stage Elderly Healthcare Insurance. We defined patients who had received triazolam for 180 days or longer during fiscal year 2011 as the triazolam group, and those who had not received any hypnotics during the period as the non-triazolam group. Each patient in the triazolam group was then matched with a unique control from the non-triazolam group according to propensity score. Multivariate conditional logistic regression analyses were used to obtain adjusted odds ratios for pneumonia, trauma, and pressure ulcer in the triazolam group compared with the non-triazolam group. RESULTS: The number of patients in the triazolam and non-triazolam groups in the unmatched cohort was 13,015 and 411,610, respectively. Adjusted odds ratios show that the risks for pneumonia, trauma, and pressure ulcer in the matched cohort increased by approximately 40%, 30%, and slightly less than 30%, respectively (all statistically significant). CONCLUSIONS: Regular use of triazolam is a risk factor for pneumonia, trauma, and pressure ulcer in older people.

Cognition-impairing effects of benzodiazepine-type drugs: role of GABAA receptor subtypes in an executive function task in rhesus monkeys.

The present studies evaluated the role of α1 and α5 subunit-containing GABAA receptors (α1GABAA and α5GABAA receptors, respectively) in the ability of benzodiazepine (BZ)-type drugs to alter performance in the cognitive domain of executive function. Five adult female rhesus monkeys (ages of 9-17years old) were trained on the object retrieval with detours (ORD) task of executive function. For the ORD task, the monkeys were required to retrieve food items from a clear box with one open end that was rotated to different positions along with varying placements of food. When the non-selective BZ triazolam and the α1GABAA-preferring agonists zolpidem and zaleplon were evaluated in the ORD task, deficits in performance occurred at doses that did not increase the latency of monkeys to initiate responding and/or increase the percentage of reaches that were incorrect (i.e., reaches in which food was not obtained). Cognition-impairing effects of triazolam and zolpidem in ORD were blocked by the α1GABAA-preferring antagonist, ßCCT, whereas the α5GABAA-preferring antagonist XLi-093 blocked the effects of triazolam but not zolpidem. While these findings suggest a role for both α1GABAA and α5GABAA receptor mechanisms, α1GABAA receptor mechanisms appear to be sufficient for impairments in executive function induced by BZ-type drugs.

Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans.

BACKGROUND: Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. METHODS: Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5mg/70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6h. RESULTS: Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM. CONCLUSION: The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse.

Cognitive effects of intramuscular ketamine and oral triazolam in healthy volunteers.

RATIONALE: Several studies have documented impairments in memory processes as a result of ketamine administration; however, few studies have compared the profile of cognitive effects of ketamine to other drugs. OBJECTIVES: The aim of this study was to compare the cognitive effects of ketamine with those of triazolam in healthy volunteers. METHODS: Doses of ketamine (0.2, 0.4 mg/kg intramuscular (i.m.)), triazolam (0.2, 0.4 mg/70 kg p.o.), and double-dummy placebos were administered to 20 volunteers under repeated measures, counterbalanced, double-blind conditions. Peak physiological, psychomotor, subjective, and cognitive effects were examined. RESULTS: Ketamine impaired balance when balance was assessed early in the task order, whereas triazolam impaired psychomotor coordination and divided attention irrespective of task order. Triazolam also tended to produce greater effects on working memory and episodic memory tasks than ketamine at doses that produced lower subjective effects and higher estimates of performance. CONCLUSIONS: Ketamine produces less cognitive impairment than triazolam at doses that produced greater subjective effects. Thus ketamine does not produce the underestimation of cognitive impairment typically seen with triazolam.

The efficacy and safety of muscle relaxants in inflammatory arthritis: a Cochrane systematic review.

OBJECTIVE: To determine the efficacy and safety of muscle relaxants in pain management in patients with inflammatory arthritis (IA). METHODS: We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and PsychINFO for randomized controlled trials in adults with IA that compared any muscle relaxant (administered via any route) to another analgesic intervention or placebo. We also searched the 2008-2009 American College of Rheumatology and European League Against Rheumatism abstracts and performed a hand search of reference lists of relevant articles. Primary outcomes were patient-reported pain relief ≥ 30% and withdrawals due to adverse events. Two authors independently assessed methodological quality and extracted data. RESULTS: Six trials (126 participants) were included in this review. All trials were deemed to have a high risk of bias. Five crossover trials evaluated benzodiazepine; 4 assessed diazepam (n = 71), and one assessed triazolam (n = 15). The sixth trial, a parallel-group study, evaluated zopiclone (non-benzodiazepine, n = 40). No trial was longer than 2 weeks and 3 single-dose trials assessed outcomes at 24 hours only. Overall, the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo (at 24 hours, 1 week, or 2 weeks) or in addition to nonsteroidal antiiflammatory drugs (at 24 hours) on pain intensity, function, or quality of life. Data from 2 trials of longer than 24-hour duration (diazepam and zopiclone, n = 74) found that participants who received a muscle relaxant had significantly more adverse events compared with those who received placebo [number needed to harm (NNTH) 3, 95% CI 2 to 7]. These were predominantly central nervous system side effects including dizziness and drowsiness (NNTH 3, 95% CI 2 to 11). CONCLUSION: Based upon the currently available evidence in patients with IA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or 1 week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over 2 weeks. However, even short-term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.

Muscle relaxants for pain management in rheumatoid arthritis.

BACKGROUND: Pain management is a high priority for patients with rheumatoid arthritis (RA). Muscle relaxants include drugs that reduce muscle spasm (for example benzodiazepines such as diazepam (Valium), alprazolam (Xanax), lorazepam (Ativan) and non-benzodiazepines such as metaxalone (Skelaxin) or a combination of paracetamol and orphenadrine (Muscol)) and drugs that prevent increased muscle tone (baclofen and dantrolene). Despite a paucity of evidence supporting their use, antispasmodic and antispasticity muscle relaxants have gained widespread clinical acceptance as adjuvants in the management of patients with chronic musculoskeletal pain. OBJECTIVES: The aim of this review was to determine the efficacy and safety of muscle relaxants in pain management in patients with RA. The muscle relaxants that were included in this review are the antispasmodic benzodiazepines (alprazolam, bromazepam, chlordiazepoxide,cinolazepam, clonazepam, cloxazolam, clorazepate, diazepam, estazolam, flunitrazepam, flurazepam, flutoprazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, midazolam, nimetazepam, nitrazepam, nordazepam, oxazepam, pinazepam, prazepam, quazepam, temazepam, tetrazepam, triazolam), antispasmodic non-benzodiazepines (cyclobenzaprine, carisoprodol, chlorzoxazone, meprobamate, methocarbamol, metaxalone, orphenadrine, tizanidine and zopiclone), and antispasticity drugs (baclofen and dantrolene sodium). SEARCH METHODS: We performed a search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 4th quarter 2010), MEDLINE (1950 to week 1 November 2010), EMBASE (Week 44 2010), and PsycINFO (1806 to week 2 November 2010). We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of reference lists of relevant articles. SELECTION CRITERIA: We included randomised controlled trials which compared a muscle relaxant to another therapy (active, including non-pharmacological therapies, or placebo) in adult patients with RA and that reported at least one clinically relevant outcome. DATA COLLECTION AND ANALYSIS: Two blinded review authors independently extracted data and assessed the risk of bias in the trials. Meta-analyses were used to examine the efficacy of muscle relaxants on pain, depression, sleep and function, as well as their safety. MAIN RESULTS: Six trials (126 participants) were included in this review. All trials were rated at high risk of bias. Five cross-over trials evaluated a benzodiazepine, four assessed diazepam (n = 71) and one assessed triazolam (n = 15). The sixth trial assessed zopiclone (a non-benzodiazepine) (n = 40) and was a parallel group study. No trial duration was longer than two weeks while three single dose trials assessed outcomes at 24 hours only. Overall the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo, alone (at 24 hrs, 1 or 2 weeks) or in addition to non-steroidal anti-inflammatory drugs (NSAIDs) (at 24 hrs), on pain intensity, function, or quality of life. Data from two trials of longer than 24 hours duration (n = 74) (diazepam and zopiclone) found that participants who received a muscle relaxant had significantly more adverse events compared with those who received placebo (number needed to harm (NNTH) 3, 95% CI 2 to 7). These were predominantly central nervous system side effects, including dizziness and drowsiness (NNTH 3, 95% CI 2 to 11).  AUTHORS' CONCLUSIONS: Based upon the currently available evidence in patients with RA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or one week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over two weeks. However, even short term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.

Drug-induced akathisia as a cause of distress in spouse caregivers of cancer patients.

OBJECTIVE: Family caregivers of cancer patients suffer from physical, psychological, and social distress and therefore are often referred to as second order patients. Akathisia is a common side effect of antipsychotics and antidepressants that causes great discomfort and even agitation and is often described by patients administered these drugs as the most distressing side effect of their treatment. Several studies of akathisia as a cause of distress in cancer patients have been reported. However, akathisia has not been reported as a cause of distress in family caregivers of cancer patients. METHOD/CASE REPORT: A 74-year-old spouse caregiver who was under treatment for major depressive disorder was not able to visit the hospital where her husband, a terminally ill cancer patient, was being treated. Initially, the spouse caregiver thought that she could not visit the hospital because of the symptoms of her depression and her grief about losing her husband. However, careful clinical examination revealed that she was suffering from akathisia in addition to her grief. RESULTS: Discontinuation of her sulpiride treatment resulted in the disappearance of her akathisia symptoms, and therefore she became able to visit the hospital and care for her terminally ill husband. SIGNIFICANCE OF RESULTS: Drug induced akathisia is a cause of distress in spouse caregivers taking certain drugs. It is important for clinicians to realize that family caregivers might suffer from not only socioeconomic, physical, and psychological problems but also side effects of medication.

Sedação consciente com triazolam em odontologia / Conscious sedation with triazolam in dentistry

O Triazolam, quando administrado por via oral, possui um rápido início de ação, duração dos efeitos relativamente curta e boa margem de segurança clínica. Desde que utilizado na dose adequada, torna-se um dos benzodiazepínicos de escolha para a sedação consciente em odontologia. O objetivo deste trabalho foi apresentar dados relacionados aos parâmetros farmacocinéticos, reações adversas, preucauções e contra-indicações e posologia do Triazolam, dando suporte ao seu uso na clínica odontológica.

Retrograde effects of triazolam and zolpidem on sleep-dependent motor learning in humans.

Drugs that act as allosteric activators at the benzodiazepine site of the gamma-aminobutyric acid (GABA(A)) receptor complex are used commonly to treat insomnia but relatively little is known of how such use affects learning and memory. Although anterograde effects on memory acquisition have been shown, possible retrograde effects on consolidation are more relevant when such agents are administered at bedtime. We tested the effects of two GABA(A) allosteric activators on sleep-dependent motor skill memory consolidation in 12 healthy male subjects. Subjects slept in a sleep laboratory for four consecutive nights (one accommodation night followed by three experimental nights). Placebo, triazolam 0.375 mg, and zolpidem 10 mg were given to each subject in counterbalanced order on the experimental nights. Polysomnographic (PSG) sleep measurement and sleep-dependent motor learning were assessed at each condition. Triazolam was associated with longer total sleep time and increased Stage 2 sleep. Both zolpidem and triazolam were associated with increased latency to rapid eye movement (REM) sleep. Overnight motor learning correlated with total sleep time in the placebo condition but not in the triazolam or zolpidem conditions. A statistically significant impairment in motor performance occurred overnight in the triazolam condition only. Triazolam, given in sufficient doses to prolong sleep in healthy people, affected overnight motor learning adversely. Zolpidem, in a dose sufficient to prolong REM onset latency but without other effects on PSG-measured sleep, degraded the relationship between total sleep time and overnight motor learning. These data indicate that non-selective or alpha1-preferring benzodiazepine site allosteric activators can interfere with sleep-dependent memory consolidation.

Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers.

RATIONALE: Illicit gamma-hydroxybutyrate (GHB) has received attention as a "date rape drug" that produces robust amnesia; however, there is little experimental evidence in support of GHB's amnestic effects. OBJECTIVES: This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers. MATERIALS AND METHODS: Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined. RESULTS: Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate. CONCLUSIONS: Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers.

Evidence of safety for individualized dosing of enteral sedation.

Fear of dentistry is a pervasive and persistent phenomenon that contributes to avoidance of dental care and results in a substantial public health problem. While the use of incremental enteral sedation has increased, there is a paucity of published evidence to evaluate its safety. This study sought to assess the safety of individualized dosing of enteral sedation for adults in the dental outpatient setting. The authors sent a mail survey to members of the Dental Organization for Conscious Sedation (DOCS) concerning their practice and practitioner characteristics. Anonymous treatment forms with monitoring records were collected from respondents and analyzed for pre-specified adverse event criteria. The majority of respondents reported practicing incremental enteral sedation for two to five years, accounting for less than 10% of their practice. Incremental enteral sedation, either alone or in combination with nitrous oxide and oxygen, was used most frequently. Monitoring with both pulse oximetry and automated blood pressure (BP) were prevalent. Triazolam was the drug used most commonly for enteral sedation. Of the 7740 cases submitted, 1686 (21.8%) met event criteria; the most frequent event was a decrease of more than 25% in diastolic BP from pre-drug baseline. Neither provider training nor the percentage of practices engaged in incremental enteral sedation were associated with any event; however, practicing incremental enteral sedation for less than 12 months was a significant predictor of any event (p = 0.001). Risk of having an event was not related to practice factors (that is, the time spent practicing incremental enteral sedation, the percentage of the practice devoted to practicing incremental enteral sedation, the number of cases performed, or the type of monitoring) or training factors. This survey represents the largest number of subjects reported in the literature concerning enteral sedation. These observations provide evidence for the safety of enteral sedation when these drugs and combinations are administered by properly-trained dentists who monitor patients with pulse oximetry, BP measurement, and direct observation.

A triazolam/amphetamine dose-effect interaction study: dissociation of effects on memory versus arousal.

RATIONALE: In addition to producing robust memory impairment, benzodiazepines also induce marked sedation. Thus, it is possible that the observed amnestic effects are secondary to more global sedative effects and do not reflect a specific primary benzodiazepine effect on memory mechanisms. OBJECTIVE: The objective was to use the nonspecific stimulant d-amphetamine to dissociate the sedative and memory-impairing effects of the benzodiazepine triazolam. MATERIALS AND METHODS: Single oral doses of placebo, triazolam alone (0.25, 0.50 mg/70 kg), d-amphetamine sulfate alone (20, 30 mg/70 kg), and triazolam (0.25, 0.50 mg/70 kg) and d-amphetamine sulfate (20, 30 mg/70 kg) conjointly (at all dose combinations) were administered to 18 healthy adult participants across nine sessions in a double-blind, staggered-dosing, crossover design. In addition to standard data analyses, analyses were also conducted on z-score standardized data, enabling effects to be directly compared across measures. RESULTS: Relative to the sedative measures, the memory measures generally exhibited a pattern of less reversal of triazolam's effects by d-amphetamine. The memory measures ranged in degree of reversal such that the most reversal was observed for reaction time on the n-back working memory task, and the least reversal was observed for accuracy on the Sternberg working memory task, with most measures showing an overall pattern of partial reversal. CONCLUSIONS: Benzodiazepines have specific effects on memory that are not merely a by-product of the drugs' sedative effects, and the degree to which sedative effects contribute to the amnestic effects varies as a function of the particular memory process being assessed.