In the wake (pun intended) of last year’s FDA warnings of next-morning impairment and the lower dosing recommendations for “Z drugs,” wouldn’t now be the perfect time for a new hypnotic to enter the marketplace?

Suvorexant, which will be marketed by Merck & Co. under the brand name Belsomra, was approved by the FDA in August 2014. It truly is a new chemical entity with a first-in-kind mechanism of action. Unlike currently marketed hypnotics, suvorexant does not exert its hypnotic effects via activity at receptors for GABA, histamine, or melatonin. Considered a “DORA” or dual orexin (OX1 and OX2) receptor antagonist, suvorexant alters the signaling of orexins. Orexins are neurotransmitters that regulate the sleep-wake cycle by promoting wakefulness through excitement of brain regions involved in arousal and attention.

But what does this mean clinically? Does it work? Is it safe? What about long-term use?

What Studies Show

Several pre-clinical trials have examined the efficacy and safety of suvorexant in 1,784 patients with insomnia, with 160 patients taking the drug for one year or longer. Compared to patients taking placebo, those taking suvorexant tended to go to sleep more quickly (depending on the study and the dosage used, an average of about two to 22 minutes faster) and spent less time awake throughout the night (on average, about 20 minutes more total sleep time). In general, the higher doses (30 mg to 40 mg) tended to be more effective than the lower doses (15 mg to 20 mg). These studies all compared suvorexant with placebo, so unfortunately there is no data allowing us to compare it with the hypnotics currently in use.

The most common side effects were somnolence, headache, abnormal dreams, and dry mouth, which were reported in about 2% to 8% of patients in the studies. There were also some rare side effects (reported in less than 1% of patients) that could become quite problematic. These include sleep paralysis (inability to speak or move for up to a few minutes during the sleep-wake transition), cataplexy (leg weakness for seconds up to a few minutes, reported both in the nighttime and daytime), and hypnagogic hallucinations (including vivid and disturbing perceptions).

The Fight for FDA Approval

An interesting part of the history of this drug is that Merck expected to gain FDA approval in the summer of 2013. However, the FDA expressed concerns about safety with the 30 mg to 40 mg dosing range Merck was proposing and denied approval. The approval finally came in August with the newer, lower dosing range of 10 mg to 20 mg nightly. The next-day driving tests requested by the FDA showed that even those who took the 20 mg dose were impaired in the morning. For this reason, the recommended dose is 10 mg nightly, however, the labeling does allow for dosage increases up to 20 mg nightly. Along with the concern for next-day impairment, the usual warnings for hypnotics also apply here: avoid alcohol and other CNS depressants, exercise caution in patients who are depressed or suicidal, monitor for behavioral changes including amnesia and complex sleep behaviors (eating, texting, sex while still sleeping).

Suvorexant will be available as 5, 10, 15, and 20 mg tablets by late 2014 or early 2015. It will be a schedule IV controlled substance (same category as zolpidem (Ambien) and temazepam (Restoril), among others) although the data thus far have not shown withdrawal and rebound upon discontinuation.

TCPR’s Verdict: Other than a new mechanism of action, there’s not much to recommend suvorexant. It likely works just fine as a sleeping pill, but there’s no reason to expect it to work better than the many hypnotics already on the market. We’re concerned that next-day impairment is a potential side effect at the highest approved dose of 20 mg, particularly since sleepless patients may decide on their own to take even higher doses. Be very clear to patients about the potential dangers of driving the next morning. Suvorexant also will likely be expensive, and only a couple of thousand people have been exposed thus far, mostly in short-term trials. This is definitely not a first line medication—nor even a second line.