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The story of modern tranquilliser drugs
Published in Adam Doble, Ian L Martin, David Nutt, Calming the Brain: Benzodiazepines and related drugs from laboratory to clinic, 2020
Adam Doble, Ian L Martin, David Nutt
The most dramatic episode in this anti-benzodiazepine crusade was the withdrawal from the market of the world’s biggest-selling hypnotic Halcion® (triazolam). Triazolam was reported to cause psychotic reactions in certain patients, albeit very few, which were considered, in the eyes of the regulatory authorities, to be an unacceptable risk in a hypnotic drug; it was consequently withdrawn in the UK and some other European countries. This tendency, on the part of both national regulatory authorities and medical opinion leaders to consider the hypnotic and anxiolytic benzodiazepines as comfort medicines, rather than life-saving or disease-preventing drugs, has produced a sharp reduction in the prescription of benzodiazepines, and the consequent incomes of their suppliers, despite the epidemiological evidence that generalised anxiety disorder has a prevalence rate of between 10% and 20% in the population (Kessler et al, 2001).
Behavioral effects of caffeine coadministered with nicotine, benzodiazepines, and alcohol
Published in B.S. Gupta, Uma Gupta, Caffeine and Behavior, 2020
Johnson et al.41 examined the day-after effects of the benzodiazepines flurazepam and triazolam. Caffeine alone enhanced early morning alertness, but also reversed drowsiness evident in mornings after benzodiazepine administration.
Medication effects on sleep
Published in S.R. Pandi-Perumal, Meera Narasimhan, Milton Kramer, Sleep and Psychosomatic Medicine, 2017
In the 1970s, benzodiazepines became available for the treatment of insomnia. These drugs are nonspecific GABA agonists and have far less overdose danger and abuse potential than barbiturate-like medications. The many drugs in this class are best viewed therapeutically based on their pharmacodynamics (Table 18.2).11 Rapid onset of action is characteristic of flurazepam (Dalmane) and triazolam (Halcion), indicating that both of these agents have excellent sleep-inducing effects. Flurazepam, like diazepam (Valium) and clorazepate (Tranzene), has the characteristic of having active breakdown products. This results in an extraordinarily long active half-life, which can approach 11 days. This prolonged effect in the elderly has been associated with increased automobile accidents and falls with hip fractures.12,13 Withdrawal from long-acting agents can be difficult, with an initial syndrome of insomnia followed by persistent anxiety that may extend beyond the half-life of the agent.
The risk of fractures, acute myocardial infarction, atrial fibrillation and ventricular arrhythmia in geriatric patients exposed to promethazine
Published in Expert Opinion on Drug Safety, 2020
Maurizio Sessa, Annamaria Mascolo, Kim Peder Dalhoff, Morten Andersen
According to the Summary of Product Characteristics promethazine was indicated during the study period for the treatment/prevention of allergic reactions/rhinoconjunctivitis, motion sickness and its related sign and symptoms (i.e. nausea/vomiting and vestibular symptoms), or insomnia. Domperidone, triazolam, loratadine, and betahistine were used as active comparators because they had similar indications. The choice of selecting multiple comparators was made because none of the drugs on the market had a spectrum of indications that perfectly matched those of promethazine. Triazolam was chosen over the other benzodiazepines approved for the short-term treatment of insomnia because is one of the mostly used in Denmark [8].
Evaluating lemborexant for the treatment of insomnia
Published in Expert Opinion on Pharmacotherapy, 2021
Benzodiazepines act by binding to a site on the GABA-A receptor and increasing the effect of the neurotransmitter GABA when it binds to this receptor [21]. This decreases neural activity and can have broad effects on central nervous system function including myorelaxation, anxiolysis, anticonvulsant effects, and sedation. Although many benzodiazepines are available and have shown efficacy in clinical trials, particularly for improving sleep duration [4,21], they are generally only indicated for short-term treatment [22,23] because of a paucity of data on long-term treatment. However, they are relatively contraindicated with opioids [22,23] and data are lacking on the risk–benefit ratio of longer term use. Additionally, there is a risk of dependence and withdrawal symptoms associated with these medications, particularly with higher doses, longer duration, older age, alcohol dependence, and use of the high-potency, short-acting options [24]. Adverse events associated with benzodiazepines can include daytime sedation, cognitive impairment, and motor impairment [25]. Although many benzodiazepines have been approved by the United States Food and Drug Administration (FDA) for treatment of insomnia (the short-acting temazepam, triazolam, and estazolam, and the longer-acting flurazepam and quazepam), the AASM clinical practice guidelines recommend only temazepam for treatment of both sleep onset and sleep maintenance insomnia, and triazolam for sleep onset insomnia [19] because they are short-acting and therefore have a lower likelihood of next day residual effects [26]. In the current United States market, the benzodiazepines are not among the agents most commonly prescribed for insomnia [27].
Incremental health care resource use and costs among adult patients with depression and treated for insomnia with zolpidem, trazodone, or benzodiazepines
Published in Current Medical Research and Opinion, 2022
Emerson M. Wickwire, Diana T. Amari, Timothy R. Juday, Feride Frech, Deval Gor, Manoj Malhotra
D + TI patients were required to have at least 1 prescription fill for a medication of interest with an FDA-approved indication for insomnia treatment or trazodone ≤100 mg or at least 1 off-label insomnia treatment claim coupled with at least 1 physician-assigned ICD-9/ICD-10 insomnia diagnosis code within 12 months prior to first insomnia medication claim. Medications of interest included zolpidem immediate-release (IR), zolpidem extended-release (ER), trazodone, and benzodiazepines (as a class). Some benzodiazepines have an FDA-approved indication for insomnia (estazolam, flurazepam, temazepam, triazolam, quazepam) while others do not (clonazepam, lorazepam, alprazolam); patients prescribed benzodiazepines without an insomnia indication were required to also have an insomnia diagnosis code. Trazodone ≤100 mg daily was the threshold identified for use in insomnia management (≥150 mg/day is the recommended dosage for treatment of depression). Patients were excluded for the following: 1. the presence of a prescription drug claim for a fill of any insomnia medication of interest within the 12-month period before the index date; 2. claims for a single insomnia treatment with ≤5 days’ supply; and 3. an index prescription for benzodiazepines and an anxiety diagnosis during the 12-month baseline period. Patients on polypharmacy with at least two of the study medications of interest used concurrently during the study period were not excluded from the sample, as they represented <4% of the total population (data not shown). Patients with claims for two or more insomnia medications of interest on the index date were assigned to a treatment group based on the following hierarchy: zolpidem ER, zolpidem IR, trazodone, benzodiazepines.