Nancy A. Melville

March 30, 2017

DALLAS – The insomnia drug suvorexant (Belsomra, Merck) appears to be safe and effective in older adults, without some of the risks and side effects commonly associated with other pharmaceutical agents, new research suggests.

"Overall, the current literature suggests that suvorexant is an effective treatment consideration for insomnia in geriatric patients. It is generally well tolerated by older adults, with few residual effects," the authors, led by Shilpa Srinivasan, MD, of the University of South Carolina School of Medicine, in Columbia, reported here at the American Association for Geriatric Psychiatry (AAGP) 2017.

Sleep disturbances are very common in persons of older age, affecting more than 50% of elderly adults. Common pharmacologic treatments, such as benzodiazepines, nonbenzodiazepine GABA-A receptor modulators, and sedating antidepressants, are associated with an increased risk of falling, cognitive impairment, and withdrawal symptoms.

Suvorexant, which entered the market in February 2015 as the first drug in its class, has a novel mechanism of action. It is a highly selective antagonist of orexin receptors, which are involved in wakefulness as part of a complex sleep and wakefulness process.

The authors identified seven studies of the drug's effects in patients older than 65 years. These included three randomized, controlled trials, two of which investigated the safety and efficacy of the drug in geriatric patients, and one evaluated potential effects on respiratory status in patients with chronic obstructive pulmonary disease (COPD).

Across the studies, geriatric patients represented about 20% to 59% of all study participants.

The overall results showed greater improvement for all ages with suvorexant over placebo in measures of sleep initiation and sleep maintenance, along with preservation of sleep architecture.

In older patients, 30 mg was considered a high dose and was more effective than 15 mg, particularly for sleep onset. Higher doses were linked to increased adverse events.

Somnolence, or drowsiness, was the most common adverse event, reported in 13% of participants, but there were no significant increases in falls compared to placebo.

No Respiratory Suppression

One study, sponsored by Merck, showed no statistically significant differences in healthy elderly patients in terms of immediate/delayed word recall upon being awoken in the middle of the night in comparison with participants who receved placebo. However, patients who were not elderly did show a next-day decrease in word recall when treated with 40-mg doses.

Another study, in patients aged 39 to 72 years, looked specifically at COPD. With doses up to 30 mg, there were no adverse effects on respiration in patients with COPD. However, an important caveat is that the study included patients with mild to moderate COPD and did not include those with more severe forms of the disease.

The authors of that study said they focused on COPD because of concern that hypnotic medications may pose higher risks for patients with respiratory disorders. The concern is that such drugs could decrease respiratory effort and blunt the arousal response to hypoxemia, leading to sleep breathing disorders, such as sleep apnea.

"These data do not suggest an overt respiratory depressant effect with 30- to 40-mg daily doses of suvorexant, up to twice the maximum recommended dose for treating insomnia in the US, in patients with mild to moderate COPD," the authors concluded.

In a study of 24 healthy elderly patients, there were no detrimental effects in driving performance related to treatment with 15- or 30-mg doses of suvorexant. Importantly, however, some participants had to prematurely stop their driving tests because of somnolence.

FDA-required product labeling suggests warning patients about next-day driving.

A subgroup analysis conducted by Merck's researchers of the clinical trials involving older patients was recently published in the American Journal of Geriatric Psychiatry.

In the pooled 3-month data from the studies, 319 patients treated with suvorexant 30 mg showed greater improvement in all polysomnographic sleep maintenance and onset endpoints, compared to placebo (n = 318).

Although suvorexant 15 mg was effective across the measures in 202 older patients, the onset effect was less evident at later time points.

The rate of discontinuations due to adverse events over months was nearly twice as high in the 30-mg group (6.4%; n = 627 treated) compared to the 15-mg group (3.5%, n = 202 treated). In the placebo group (n = 469), the discontinuation rate was 5.5%.

Somnolence was the most common adverse event, reported in 8.8% of patients with 30 mg, 5.4% with 15 mg, and 3.2% for placebo.

No Standard of Care

Commenting on the findings for Medscape Medical News, Raj Tampi, MD, professor of psychiatry at Case Western Reserve University School of Medicine, in Cleveland, Ohio, noted that for the treatment of insomnia, cognitive-behavioral therapy is the preferred first-line treatment. However, treatment in older patients can be more complicated.

"Unfortunately, there is no standard of care for treating sleep disorders in older adults," said Dr Tampi, program chair for the AAGP meeting.

"We would prefer to not prescribe older patients some of the medications that are approved for younger adults, due to their side effects, so cognitive-behavioral therapy would be the preferred first-line choice for insomnia. However, some settings you may not have a trained staff to provide that."

In cases that do require pharmacologic treatment, suvorexant appears to be a potentially better choice than other options.

"Suvorexant shows a somewhat benign side-effect profile compared to the other drugs, with sedation appearing to be the only significant side effect, and no problems with addiction or increases in falls or cognitive decline.

"However, there are only two randomized controlled trials involving older adults, so that needs to be considered."

The investigators and Dr Tampi have disclosed no relevant financial relationships.

American Association for Geriatric Psychiatry (AAGP) 2017. Abstract NR-36, presented March 25, 2017.


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