Suvorexant (Belsomra) for Insomnia: One Difficult Sentence

The next issue of The Medical Letter (March 2, 2015) leads off with an article on a new drug with a new mechanism of action for treatment of insomnia. Suvorexant (Belsomra – Merck) is the first orexin receptor antagonist. Signaling of orexin neuropeptides sustains wakefulness; suvorexant promotes sleep by blocking orexin neuropeptides from binding to their receptors. Loss of orexin signaling has been associated with narcolepsy and cataplexy (that is, narcolepsy with cataplexy is associated with absence of orexin, and orexin knockout mice develop narcolepsy). One sentence in our article (repeated in the conclusion) states that cataplexy-like symptoms have occurred in patients treated with suvorexant in clinical trials. We spent a lot of time thinking about that sentence.

No patients treated with suvorexant have developed narcolepsy, and perhaps none ever will, but some patients have developed symptoms that resemble cataplexy. The FDA Medical Review of Belsomra, which is 374 pages long, devotes 3 pages to the subject of cataplexy. The sponsor of the clinical trials (Merck) reported to the FDA that the possibility of cataplexy was considered in 45 patients, but an expert adjudication committee concluded that none of them had cataplexy. The FDA was not so sure about that. One patient, who reported episodes of leg weakness that came on while laughing (a known trigger for cataplexy), seemed especially concerning, but at least 3 other patients reported lower limb muscle weakness that resembled cataplexy, in the opinion of the FDA reviewing officer.

In addition, several patients treated with suvorexant (some in higher doses than are now recommended) and none treated with placebo developed hallucinations or sleep paralysis, both of which occur in narcolepsy. And some patients developed excessive daytime sleepiness that could be considered close to sleep attacks; one man had to pull over and stop the car he was driving. How far should we have gone in describing these few events, and how should they be characterized? That is a difficult question. We left it at cataplexy-like symptoms have occurred, but included it in our conclusion. Will patients who take suvorexant develop narcolepsy? Some of our reviewers said they will not, and we thought they might be right. Time will tell.

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  1. Francis Dann says:

    There was an article in the BMJ last year suggesting that many drugs used for insomnia greatly increase the risk for Alzheimer’s disease, and on a usage-related basis.

    We are now then in desperate need for agents to help with sleeplessness–because all remaining agents are associated with worrisome adverse events.

    Is suvorexant going to meet this goal, or will it be another risky agent?

  2. Pam harrell says:

    I took belsomra and I have narcolepsy with cataplexy. I wasn’t told I wasn’t suppose to take it. I took 10 mil and had cataplexy. I hate cataplexy its a felling like your muscles can’t support your weight and you have to sit or lye down. It’s terrible. The next day my muscles were still week and I couldn’t function.
    But what are the main reasons people like me aren’t suppose to take it? Are there other things that affect us from this drug compared to others

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