Search Results (6)

Currently, approximately 40% of patients with dementia develop some form of sleep disorder. Benzodiazepines are widely prescribed but pose the risk of tolerance and cognitive decline; however, Z-drugs may offer safer alternatives. Therefore, this systematic review aimed to analyze the effect of benzodiazepines and Z-drugs on sleep disorders in patients with dementia. Two authors conducted a systematic search in PubMed, Scopus, Web of Science, Espistemonikos, and ACCESSSS for studies published between 2019 and 2024 using the MeSH terms “dementia”, “sleep disorders”, and “pharmacotherapy”. Randomized clinical trials comparing benzodiazepines, Z-drugs, or innovative medications with placebo or other drugs were included. Sleep and cognitive outcomes were assessed using validated instruments; the ROB-2 tool evaluated the risk of bias. The protocol was registered in “PROSPERO”. Three randomized clinical trials involving a total of 192 patients were included in the review. Zopiclone increased the main duration of nighttime sleep by 81 min, Zolpidem reduced nighttime awakenings by 21 min, and Eszopiclone improved sleep quality, benefited the progression of sleep architecture, and reduced mental symptoms such as fear and anxiety. Z-drugs show superior efficacy and safety over benzodiazepines, improving sleep and cognitive symptoms in dementia. Personalized treatment and further research across dementia subtypes are needed to optimize long-term outcomes. Full article

Insomnia is the most prevalent sleep disorder, affecting millions worldwide and taking a heavy toll on patient health with significant social and economic impact. Even though there are multiple different types of insomnia medications and behavioral therapies, there are still many individuals for whom treatment remains ineffective. The objective of this retrospective study was to analyze the effectiveness of daridorexant in a cohort of chronic insomnia patients largely transitioned from GABA-A positive allosteric modulators (benzodiazepines, zolpidem or eszopiclone) or other frequently prescribed insomnia medications (including trazodone, atypical antipsychotics or tricyclic antidepressants). A total of 86 patients were treated in the course of ordinary practice and the primary analytic endpoint was the change in Insomnia Severity Index (ISI) score following ≥ 30 nights of treatment with daridorexant. Results from 80 of the 86 patients with full data (65% female, mean age 53.5 years, 18.8% with comorbid obstructive sleep apnea, 91.3% transitioned from a different medication) showed a mean improvement in ISI score of 7.0 ± 0.54 points (SEM) (p < 0.0001) from 18.0 to 11.0. Overall, 78% of the cohort demonstrated a clinically meaningful improvement as defined by at least a six-point drop in ISI. Total sleep time increased by 54 ± 1.0 min (SEM) (p < 0.0001) from 6.0 h to 6.9 h. Mean sleep latency decreased by 23.9 ± 2.4 min (SEM) (p < 0.0001) from 58.8 min to 34.9 min. Wake after sleep onset decreased by 31.6 ± 3.2 min (SEM) (p < 0.001) from 42.8 min to 11.3 min. Sleep efficiency improved by 10.5 ± 1.1% (SEM) (p < 0.0001) from 79.3% to 89.8%. No significant adverse events were noted during the study duration. Keeping in mind this study’s limitations, these data suggest that for insomnia patients with an incomplete response to current therapy, switching to daridorexant is safe and may be an effective alternative treatment. Full article

Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1–2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success. Full article

While evidence supports the benefits of medications for the treatment of chronic insomnia, there is ongoing debate regarding their appropriate duration of use. A panel of sleep experts conducted a clinical appraisal regarding the use of insomnia medications, as it relates to the evidence supporting the focus statement, “No insomnia medication should be used on a daily basis for durations longer than 3 weeks at a time”. The panelists’ assessment was also compared to findings from a national survey of practicing physicians, psychiatrists, and sleep specialists. Survey respondents revealed a wide range of opinions regarding the appropriateness of using the US Food and Drug Administration (FDA)-approved medications for the treatment of insomnia lasting more than 3 weeks. After discussion of the literature, the panel unanimously agreed that some classes of insomnia medications, such as non-benzodiazepines hypnotics, have been shown to be effective and safe for long-term use in the appropriate clinical setting. For eszopiclone, doxepin, ramelteon and the newer class of dual orexin receptor antagonists, the FDA label does not specify that their use should be of a limited duration. Thus, an evaluation of evidence supporting the long-term safety and efficacy of newer non-benzodiazepine hypnotics is timely and should be considered in practice recommendations for the duration of pharmacologic treatment of chronic insomnia. Full article

Background: Symptoms of sleep disorders, such as disturbances in sleep initiation and continuity, are commonly reported in patients with schizophrenia, especially in the acute phase of illness. Studies have shown that up to 80% of patients diagnosed with schizophrenia report symptoms of insomnia. Sleep disturbances have been shown to increase the risk of cognitive dysfunction and relapse in patients with schizophrenia. Currently, there are no medications approved specifically for the treatment of insomnia in patients with schizophrenia. Methods: A literature search was performed through OVID and PubMed to compile publications of pharmacotherapy options studied to treat insomnia in patients with schizophrenia. Articles were reviewed from 1 January 2000 through 1 March 2018 with some additional earlier articles selected if deemed by the authors to be particularly relevant. Results: Pharmacotherapies collected from the search results that were reviewed and evaluated included melatonin, eszopiclone, sodium oxybate, and antipsychotics. Conclusions: Overall, this review confirmed that there are a few evidence-based options to treat insomnia in patients with schizophrenia, including selecting a more sedating second-generation antipsychotic such as paliperidone, or adding melatonin or eszopiclone. Further randomized controlled trials are needed. Full article

RP 48497 is a photodegradation product of eszopiclone, a non-benzodiazepine sedative-hypnotic used in the treatment of insomnia. We report herein the first synthesis of RP 48497 via reduction, chlorination, and recyclization of 6-(5-chloropyridin-2-yl)-7-hydroxy-6,7-dihydropyrrolo[3,4-b]pyrazin-5-one (3), a key intermediate in the synthesis of eszopiclone. The structure of RP 48497 was confirmed by its ¹H-NMR and MS data. The mechanism of the reduction step in the synthesis of RP 48497 was also studied and the key parameters were determined. These findings should be important for quality control purposes in the manufacture of eszopiclone. Full article