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Benzodiazepine drugs in sleep disorders
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
It appears that atypical hypnotics may be associated with fewer rebound effects on stopping treatment than are traditional benzodiazepine hypnotics (Lader, 1992). For example, a study in healthy volunteers (Lader and Frcka, 1987) showed minimal rebound effects for zopi-clone compared with temazepam. Similar findings have been observed in insomniac patients when zopiclone has been compared with triazolam, nitrazepam or flurazepam (Bianchi and Musch, 1990; Elie et al, 1990; Fleming et al, 1990), although there is a clear recrudescence of the original insomnia upon stopping zopiclone treatment in some of these studies.
Sedative and Hypnotic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Arup Kumar Misra, Pramod Kumar Sharma
Eszopiclone, an S(+) enantiomer of zopiclone acts by enhancing the benzodiazepine binding site of GABAA receptor to promote its positive effects on sleep (Benjamin, 2006). It is usually used for long-term management of insomnia (nearly 12 months), thus differs its pharmacological actions from other Z compounds. It maintains sleep and also decreases the time to fall asleep. It has bioavailability of about 80%. Nearly 50–60% of its drug is bound to plasma proteins with a plasma half-life of nearly 6 h. Hepatic cytochromes CYP3A4 enzymes metabolized the drug to inactive metabolites, namely, N-oxide derivative and desmethyl eszopiclone, respectively (Benjamin, 2006). In elderly, the excretion of the drug is prolonged due to increase in elimination half-life. Eszopiclone administered with CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, etc.) decrease its metabolism thus increasing its elimination half-life, whereas if coadministered with inducers of CYP3A4 (e.g., rifampin), the hepatic metabolism will increase leading to decrease in elimination half-life. The drug is available in the dosage of 1 mg, 2 mg, and 3 mg tablets. No tolerance or withdrawal syndrome is seen on discontinuation of the drug. Minor symptoms of withdrawal like abnormal dreams, anxiety, nausea, and upset stomach are seen in less than 2% of the patients taking the drug for management of sleep disorder (Atkin et al., 2018).
Safer Prescribing: The Threat and Challenge of Caring for People with Chronic Pain
Published in James Matheson, John Patterson, Laura Neilson, Tackling Causes and Consequences of Health Inequalities, 2020
Clarissa Hemmingsen, James Matheson
Over the last 5 years, spending on hypnotics like zopiclone and zolpidem has decreased but the rates of prescription have remained similar [39]. The number of deaths involving zopiclone and zolpidem continue to rise, from 96 in 2016 to 127 in 2017 and, as with benzodiazepines, in 8 out of 10 deaths, mixing with other drugs was implicated [30]. Higher levels of anxiolytic and hypnotic medications have long been understood to be associated with areas of deprivation [40]. In the UK there has been a widespread perception among doctors that z-drugs are safer than benzodiazepines though they share similar risks of respiratory effects including respiratory depression, especially when taken with alcohol [41]; addiction, with evidence of withdrawal symptoms after 3 weeks, less than its licensed duration of treatment [42], tolerance and misuse potential [43]. There is a high risk of rebound insomnia when stopped after longer-term use. Pharmacologically, zopiclone is known for its low index of fatal toxicity [44], as low or lower than benzodiazepines [45,46]. One American review found the mortality risk associated with taking a hypnotic to be equivalent to smoking a pack of cigarettes a day [47]. In the US the Food and Drug Administration has placed a high-risk warning on the z-drugs after multiple reports of people being injured or killed by unconscious behaviours whilst on the medications including through activities such as cooking, driving and shooting themselves [48].
Pharmacological and non-pharmacological treatment options for sleep disturbances in Alzheimer’s disease
Published in Expert Review of Neurotherapeutics, 2023
Binish Javed, Amaan Javed, Chia Siang Kow, Syed Shahzad Hasan
Zopiclone and Zolpidem are Z-drugs frequently prescribed for insomnia in patients with late-onset Alzheimer’s disease. Louzada et al. [61], in a randomized triple-blind placebo-controlled trial, showed that zopiclone (81-minute decrease in main nocturnal sleep duration (MNSD); 26-minute drop in awake time after sleep onset (WASO)) and zolpidem (no significant difference in MNSD; 22-minute drop in WASO) had clinical benefit when used short-term even though there was a need for further evaluation of safety. In a prospective study by Huo et al. [62], eszopiclone improved sleep quality and cognition in elderly patients with dementia and insomnia. A usual daily oral dose of Zolpidem is 5–10 mg, and the usual daily maximum dose is 10 mg. The usual dosage of Zopiclone is 2–3 mg, with a usual daily maximum of 3 mg [5].
A primer on sleeping, dreaming, and psychoactive agents
Published in Journal of Social Work Practice in the Addictions, 2023
Cyclopyrrolones, otherwise known as Z-drugs, while pharmacologically distinct from benzodiazepines, still bind to GABA receptors. The most prominent feature of Z-drugs is that they decrease sleep latency and increase the duration of sleep. The duration of stage one sleep is shortened, while the time spent in stage two sleep is typically increased. In most studies, stage three sleep tended to be increased, but no change and actual decreases was observed in clinical trials. The effect of zopiclone on stage three sleep differed from that of traditional benzodiazepines, which suppress slow-wave sleep. While the onset of REM sleep was delayed, this drug group does not appear to reduce the total duration of REM sleep, according to pharmaceutical agency sponsored studies (Nu-Pharm, 2009; Sanofi-Aventis, 2018). However, in 2014 Health Canada placed a recommended dosage limitation on the use of zopiclone due to the adverse behaviors its users were experiencing, including impairments lasting for up to two days. Amnesia can result from using this drug, as highlighted by reports of people getting out of bed, while not fully awake after taking cyclopyrrolones and unknowingly engaging in activities, with no memory of the action the next day (Sanofi-Aventis, 2018).
Comparison of psychotropic medication use in the Baltic countries
Published in Nordic Journal of Psychiatry, 2020
Jaanus Harro, Kaire Aadamsoo, Ly Rootslane, Ott Laius, Aet O’Leary, Virginija Adomaitiene, Biruta Kupca, Andres Lehtmets, Alvydas Navickas, Elmars Rancans, Maris Taube, Elmars Terauds, Kadri Pops
The Nordic countries have been using significantly more of hypnotics than anxiolytics. The levels of use of both, especially hypnotics, have recently declined in Finland, but Finland still uses these drugs at the level of Lithuanian anxiolytics and Estonian hypnotics use combined. In Norway, the use of anxiolytics has declined but hypnotics use has remained stable, the former is at about the level of Estonia but the latter twice the level of this comparator. In Sweden, the use of anxiolytics is about the same as in Estonia and Latvia, while the use of hypnotics is between that of Norway and Finland. Zopiclone was the by far most prescribed hypnotic medicine in Estonia. Since 2005 when the use of zopiclone was similar to diazepam and alprazolam the prescription rate has been steadily increasing [27]. Benzodiazepines are more frequently used by older people and by females but the populations in the Baltic Countries are similar in such demographic aspects. The remarkable consumption level of lorazepam in Lithuania has a long tradition, and in this tradition even other medicines classified as anxiolytics are often used as sleep aid, often for rather long periods at low doses.