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Dangers of Sleep Drug Suvorexant Still Outweigh Minimal Benefits

Worst Pills, Best Pills Newsletter article December, 2016

In the November 2014 issue of Worst Pills, Best Pills News, we profiled suvorexant (BELSOMRA), the then-recently-approved sleep medicine.[1] Public Citizen’s Health Research Group had opposed suvorexant’s approval in testimony at a Food and Drug Administration (FDA) advisory committee meeting[2] and in a subsequent letter to the FDA[3] because the drug’s risks outweigh its minimal benefits.

Since suvorexant’s approval, hundreds of cases of side effects linked to the drug have been...

In the November 2014 issue of Worst Pills, Best Pills News, we profiled suvorexant (BELSOMRA), the then-recently-approved sleep medicine.[1] Public Citizen’s Health Research Group had opposed suvorexant’s approval in testimony at a Food and Drug Administration (FDA) advisory committee meeting[2] and in a subsequent letter to the FDA[3] because the drug’s risks outweigh its minimal benefits.

Since suvorexant’s approval, hundreds of cases of side effects linked to the drug have been reported to the FDA. Suvorexant’s maker, Merck, continues to aggressively market the drug to the tens of millions of Americans with chronic insomnia, despite the fact that nondrug approaches are the only effective and, more importantly, sustainable solutions for both occasional and persistent insomnia.

Evidence on safety and effectiveness

Chronic insomnia affects about 10 percent of Americans, and more than one-quarter of the U.S. population reports occasional trouble getting enough sleep.[4] A number of sleep drugs — including the popular drug zolpidem (AMBIEN, EDLUAR, INTERMEZZO, ZOLPIMIST) — have been approved in the past two decades to treat insomnia. A 2012 analysis showed that these medicines reduced the time to fall asleep by an average of just 22 minutes, while as a group, they did not increase total sleep time or reduce the number of nighttime awakenings. [5] We have designated all of these as Do Not Use.

Suvorexant is the first in a new class of sleep drugs that purportedly suppresses “wakefulness” signals in the brain,[6] but it is no better than its predecessors in terms of its very modest benefits on sleep. In two studies conducted before suvorexant’s approval, the maximum approved dose reduced the time to fall asleep by an average of just 5-8 minutes, increased total sleep time by just 11-22 minutes and reduced nighttime awakenings by just 16-31 minutes over the course of a night’s sleep.[7] These studies did not even adequately test the lower, 10 mg nightly dose ultimately approved by the FDA — meaning the prescribed dosage of the drug is likely to be even less effective.

Furthermore, sleep medicines have long been associated with next-day drowsiness, driving impairment and car accidents.[8],[9] For this reason, the FDA required tests on subjects’ driving ability the morning after taking a dose of suvorexant. One of the two studies showed that subjects given suvorexant significantly deviated from their driving lane, while four of the 28 subjects even had to stop the test due to sleepiness.[10]

Because these and other risks were greater at higher doses (30 mg and 40 mg) of the drug, the FDA ultimately approved a lower, 10 mg starting dose and a 20 mg maximum dose.[11] However, the 10 mg starting dose was studied in just 81 subjects for up to a month.[12] In that trial, on average, subjects did not fall asleep any more quickly, spent just 5 percent more of their time in bed asleep and awoke only 21 minutes less during the night. The 20 mg dose had similarly modest benefits, in addition to causing significant next-morning sleepiness and driving impairment in the preapproval studies.

In the absence of any new studies of suvorexant since its approval, postmarketing adverse event reports submitted by patients and health care practitioners to the FDA are as-yet the only additional source of data on the drug’s safety.

In January 2016, the Institute for Safe Medication Practices published an analysis of more than 1,000 of these reports submitted to the FDA in just the first half of 2015.[13] The most common complaint, unsurprisingly, was that the drug was ineffective. Other commonly reported side effects with suvorexant were nightmares, hallucinations, daytime sleepiness, headache, fatigue, dizziness and — surprisingly, given the drug’s depressant qualities — anxiety, agitation, nervousness and irritability.

This troubling risk-benefit balance has not stopped Merck from aggressively marketing the drug to consumers. In 2015, the U.S.-based company spent $96 million advertising suvorexant, making the drug one of the top 20 most heavily advertised drugs in the U.S. that year.[14] Part of this money was spent on direct-to-consumer television ads and purported “informational” websites that do not mention suvorexant by name[15] but are meant to encourage patients with symptoms of insomnia to seek out treatment. One of these websites, whysoawake.com, directs users to the drug’s official promotional site.[16]

What You Can Do

Do not use suvorexant or any other drug for insomnia; we have listed all sleep drugs as Do Not Use. There are many things you can do to sleep better and longer without resorting to drugs (see box, below).

Steps to Improve Sleep Hygiene
  1. Avoid the use of caffeine- containing products (including tea, coffee, and chocolate), nicotine and alcohol, especially later in the day.
  2. Avoid heavy meals within two hours of bedtime.
  3. Avoid drinking fluids after supper to prevent frequent nighttime urination.
  4. Avoid environments that will make you active after 5 p.m. (for example, avoid noisy environments).
  5. Only use your bed for sleep. Sit in a chair when you just want to relax.
  6. Avoid watching television in bed (for example, watch it in your chair).
  7. Establish a routine for getting ready to go to bed.
  8. Set time aside to relax before bed, and utilize relaxation techniques.
  9. Create an atmosphere conducive to sleep: Keep yourself at a comfortable temperature by modifying the number of blankets you use. Use earplugs if it is too noisy. Make the room darker if there is too much light (for example, close the door). Replace the mattress. on your bed if it is uncomfortable.
  10. When in bed, relax and think pleasant thoughts to help you fall asleep.
  11. Get up at the same time every day, including weekends. Use an alarm clock if it will help.
  12. Avoid taking daytime naps. If you have to take them, make sure that you do so before 3 p.m. and that the total time napping does not exceed one hour.

If you have persistent or severe insomnia, you should see your physician to be evaluated for treatable diseases, such as sleep apnea and depression, which may be causing your sleep trouble. Never stop any drug without first talking with your doctor.

Never stop any drug without first talking with your doctor.

References

[1] FDA approves suvorexant, latest dangerous sleep drug. Worst Pills, Best Pills News. November 2014. http://www.worstpills.org/member/newsletter.cfm? n_id=930. Accessed October 8, 2016.

[2] Public Citizen. Testimony to the FDA Peripheral and Central Nervous Systems Drugs Advisory Committee on Suvorexant. May 22, 2013. http://www.citizen.org/hrg2129. Accessed October 8, 2016.

[3] Public Citizen. Letter to the FDA Opposing Approval of the Sleep Medicine Suvorexant. June 14, 2013. http://www.citizen.org/hrg2136. Accessed October 8, 2016.

[4] Centers for Disease Control and Prevention. Sleep and Sleep Disorders. http://www.cdc.gov/sleep/index.html. Accessed October 8, 2016.

[5] Huedo-Medina TB, Kirsch I, Middlemass J, et al. Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: Meta-analysis of data submitted to the Food and Drug Administration. BMJ. 2012;345:e8343.

[6] Food and Drug Administration. Briefing Document for the Peripheral and Central Nervous Systems Advisory Committee to discuss the approval of suvorexant, at PDF p. 3. May 22, 2013. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMe etingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee /UCM352969.pdf. Accessed October 8, 2016.

[7] Ibid., at PDF p. 5-9.

[8] Gustavsen I, Bramness JG, Skurtveit S, et al. Road traffic accident risk related to prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and nitrazepam. Sleep Med. 2008;9(8):818-822.

[9] Orriols L, Philip P, Moore N, et al. Benzodiazepine-like hypnotics and the associated risk of road traffic accidents. Clin Pharmacol Ther. 2011;89(4):595-601.

[10] Food and Drug Administration. Briefing Document for the Peripheral and Central Nervous Systems Advisory Committee to discuss the approval of suvorexant, at PDF p. 33. May 22, 2013. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMe etingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee /UCM352969.pdf. Accessed October 8, 2016.

[11] Merck & Co. Label: suvorexant (BELSOMRA). http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204 569s001lbl.pdf. Accessed October 8, 2016.

[12] Food and Drug Administration. Briefing Document for the Peripheral and Central Nervous Systems Advisory Committee to discuss the approval of suvorexant, at PDF p. 180. May 22, 2013. href="http://www.fda.gov/downloads/AdvisoryCommittees/Commit teesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCom mittee/UCM352969.pdf . Accessed October 8, 2016.

[13] Institute for Safe Medication Practices. Quarter Watch. January 13, 2016. https://www.ismp.org/quarterwatch/pdfs/2015Q2.pdf. Accessed October 8, 2016.

[14] Robbins R. Drug makers now spend $5 billion a year on advertising. Here’s what that buys. STAT. March 9, 2016. https://www.statnews.com/2016/03/09/drug-industry- advertising/. Accessed October 8, 2016.

[15] Cohn J. Drugs you don’t need for disorders you don’t have. The Huffington Post: Highline. http://highline.huffingtonpost.com/articles/en/sleep- advertising/. Accessed October 8, 2016.

[16] Merck. Why So Awake? http://www.whysoawake.com/sleep-experts/. Accessed October 8, 2016.

Disclaimer

The information on this website is not intended to substitute for professional medical advice, diagnosis, or treatment. Consult your doctor before changing or discontinuing any medication.