Showing posts sorted by relevance for query suvorexant. Sort by date Show all posts
Showing posts sorted by relevance for query suvorexant. Sort by date Show all posts

Wednesday, June 24, 2020

Suvorexant May Improve Insomnia With Alzheimer Disease

In continuation of my update on Suvorexant


Suvorexant improves total sleep time (TST) in patients with probable Alzheimer disease (AD) dementia and insomnia, according to a study published online Jan. 15 in Alzheimer's & Dementia.

W. Joseph Herring, M.D., Ph.D., from Merck & Co., in Kenilworth, New Jersey, and colleagues randomly assigned patients with both probable AD dementia and insomnia to four weeks of suvorexant 10 mg (136 patients; could be increased to 20 mg based on clinical response) or placebo (141 patients). Overnight polysomnography in a sleep laboratory was used to assess TST.
The researchers found that at week 4, the mean improvement from baseline in TST was 73 minutes for the suvorexant group and 45 minutes for the placebo group. Patients taking suvorexant were twice as likely to show an improvement of ≥60 minutes in TST compared with those taking placebo. In suvorexant-treated patients, somnolence was reported by 4.2 percent of participants versus 1.4 percent of placebo-treated patients.
"Suvorexant did not appear to impair next-day cognitive or psychomotor performance as assessed by objective tests, although these assessments do not constitute a comprehensive assessment of cognition," the authors write.
Several authors disclosed financial ties to pharmaceutical companies, including Merck, which manufactures suvorexant and funded the study.
https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12035

https://en.wikipedia.org/wiki/Suvorexant

Wednesday, December 12, 2012

Drug offers alternative treatment strategy for insomnia


In continuation of my update on  suvorexant

The team, led by W Joseph Herring (Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, USA), studied the effects of the orexin receptor antagonist suvorexant in treating 254 people aged 18 to 64 years with moderately severe insomnia.

The participants were randomly assigned to take either suvorexant, at doses of 10, 20, 40, or 80 mg, or placebo for 4 weeks, after which they switched to the alternative treatment for a further 4 weeks.

Their sleep was monitored in a sleep laboratory on the first night of taking each treatment and again in the fourth week of each treatment.

Sleep efficiency, reflecting the time patients spent in bed at night asleep, was an average 66% (with an average total sleep time of 316 minutes) before treatment and improved by a significant 5.2% to 12.9% on the first night of treatment with suvorexant, compared with placebo.


Suvorexant (see structure)  treatment also resulted in patients experiencing 21 to 37 fewer minutes awake during the first night when compared with placebo.

The benefits of suvorexant were maintained over the 4 weeks of the study, with a significant 4.7% to 10.4% improvement in sleep efficiency, compared with placebo.

For both outcomes, the effect was dose-related and all doses were superior to placebo for improving sleep efficiency on night 1 and at the end of week 4. Dose-related effects were also seen for sleep induction (latency to persistent sleep) and maintenance (wake after sleep onset). The researchers note that, overall, suvorexant was well tolerated. The most common adverse event associated with the drug was somnolence, which showed a dose-related increase.

But there was no consistent evidence of rebound insomnia or withdrawal effects after 4 weeks of treatment, or for next-day residual effects.

"This study provides evidence that suvorexant may offer a successful alternative strategy for treating insomnia," Herring said in a press statement.

Sunday, August 26, 2012

Insomnia Drug Closer to Approval | News | Drug Discovery and Development Magazine

Merck & Co. said that its experimental insomnia drug suvorexant (see structure) helped patients fall asleep faster and stay asleep longer in two late-stage tests of the drug, seen as a potential blockbuster in a multibillion-dollar market. 

Merck said the drug worked better than a placebo at measurements including total sleep time, time to falling asleep, and continuous sleep after one month and three months of treatment. The company said patients reported better results on suvorexant compared with placebo, and their sleeping habits also were measured electronically.

Suvorexant is a new type of insomnia drug designed to help patients sleep while minimizing morning grogginess. It is one of Merck's major drug candidates. The company plans to file for U.S. marketing approval this year, and it is one of six planned product filings for Merck in 2012 and 2013.

The two trials involved more than 2,000 patients who had insomnia that was not caused by another medical problem. The most common side effects of suvorexant were tiredness and headache.
 

Thursday, July 25, 2013

Friday, February 22, 2019

New class of sleeping pill preserves ability to wake in response to danger signals


2D chemical structure of 1088991-95-0

https://chem.nlm.nih.gov/chemidplus/rn/1088991-95-0

In a trial of one of the main class of prescription sleeping pills, half the participants slept through a fire alarm as loud as someone vacuuming next to their bed. But a newer alternative preserves the ability to wake in response to danger signals, according to a new research.
Published this week in Frontiers in Behavioral Neuroscience, the study showed that mice given the experimental hypnotic drug DORA-22 wake as quickly when threatened as drug-free sleepers - and then fall back asleep as quickly as ones given standard sleeping pills, once the threat is gone.

Common sleeping pills muffle your sleeping brain's 'intruder alert'

Even during sleep the brain continuously processes sensory information, waking us if it detects a threat. But the most widely prescribed class of sleeping pills, known as benzodiazepines, makes us less likely to rouse in response to sensory input.
"Benzodiazepines stimulate the widespread brain receptor GABA-A, which makes us sleepy but also suppresses off-target brain areas - including the 'gatekeeper' that decides which sensory inputs to process," explains study senior author Professor Tomoyuki Kuwaki of Kagoshima University, Japan.
Over the last decade, researchers have been developing a new class of hypnotic drugs called dual orexin receptor antagonists (DORAs). DORAs more selectively target the brain's sleep/wake pathways, which gives them safety advantages over benzodiazepines. These include a reduced 'hangover effect', with DORAs less likely to affect driving ability the day after use.
Kuwaki and colleagues hypothesized that the selectivity of DORAs could make them a safer alternative during sleep as well - by allowing the brain's sensory gatekeeper to stay vigilant to threats.

DORA-22 allows mice to wake to a threat, but still helps them sleep

The group tested their theory in mice.
The mice were dosed and tested after dark, when they are normally most active. One group was administered DORA-22, another a benzodiazepine called triazolam - and a third group was given placebo as a control.
"DORA-22 and triazolam had similar sleep promoting effects, extending the duration of deep sleep by 30-40% compared to placebo," reports Kuwaki.
One to four hours after dosing, the deep-sleeping mice were presented with a threatening stimulus: the smell of a fox, a high-pitched noise like a dog whistle, or trembling of their cage. The trembling frequency was designed to match that of an earthquake - a serious threat in Kuwaki's native Japan and many other parts of the word.
"As expected, arousal in response to these threatening stimuli was delayed significantly in the triazolam treatment, but not in the DORA-22 treatment, compared to placebo.
Even more promising, the sleep-promoting effect of DORA-22 remained after the rude awakening.
"Even though the DORA-22-treated mice were quickly woken by a threat, they subsequently fell back asleep as quickly as with triazolam, and significantly faster than with placebo."
To help demonstrate that the delay in waking to a threat during triazolam treatment was due specifically to inhibition of sensory gating in the brain, the researchers also tested the sleeping mice with a non-sensory stimulus.
"The three groups woke equally quickly when we suddenly reduced the amount of oxygen in their cage. This suggests that the delay in rousing to threatening stimuli caused by triazolam was not caused by a general inhibition of waking systems in the brain."

Human studies are needed to confirm DORA safety and efficacy

"Although it remains to be seen whether DORAs have the same properties when used in humans, our study provides important and promising insight into the safety of these hypnotics."
Since 2014, another DORA called surovexant has gained regulatory approval in Japan, the USA and Australia. So far, the high cost and limited clinical testing of surovexant have limited its use, amid concerns that doses high enough to significantly improve sleep lead to drowsiness the following day. New DORAs currently in development could overcome this hangover effect if they are cleared more quickly from the body than suvorexant, so that their effects are less likely to last beyond bedtime. Keep your eyes peeled.