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Clinician’s Corner: Sleep aids not related to Benzodiazepines

Sleep aids not related to Benzodiazepines

Melatonin receptor agonists:

Melatonin is a hormone synthesized in the pineal gland, that is responsible to make us fall asleep. It is produced from tryptophan. No surprise that the pineal gland starts to function after 6 months, when babies start sleeping during the night.  Pineal gland function declines as we age… no surprise their either! There are two types of melatonin receptors:

  • MT1 receptor: activation of the MT1 receptor causes sleepiness
  • MT2 receptor: activation is related to light-dark synchronization, causing our natural circadian rhythms.

Ramelteon  (Rozerem®)

Mechanism: selectively binds to the MT1 and MT2 receptors, inhibiting the neuronal firing that maintains wakefulness.  Is NOT a CNS depressant. It is not a scheduled drug. Ramelteon shows no evidence of abuse, dependence or withdrawal, or rebound insomnia.

Indications: for insomnia characterized with difficulty of sleep onset. Can be prescribed long term.

Avoid in patients with severe liver impairment.  Avoid with alcohol. May cause decreased testosterone levels.

Patient information:

  • Take 30 minutes before bed and activities confined to preparing for bed.
  • Avoid hazardous activity (driving etc.) after taking
  • Do not take with, or immediately after a high fat meal.
  • Report cessation of menses, decreased sex drive, and fertility problems.

Melatonin (available Over The Counter)

Available as 1mg, 3mg 5mg and 10mg capsules/tablets

Melatonin is non-scheduled, non-habit forming and available over-the counter.

Dose 1 to 10mg at bedtime.  Don’t exceed 10mg.

There is a slight increase for bleeding risk with melatonin.  Monitor in suspect patients, frail, elderly, or patients that are on blood thinners.

Jet lag:  Melatonin can improve some symptoms of jet lag, such as alertness and psychomotor performance, may also be useful for daytime sleepiness and fatigue. Think of interaction with MT2 receptor.

Hetlioz®  (tasimelteon)             cost about $10,000/month)

Is another melatonin agonist that is only approved for non-24 sleep-wake disorder, where patients can’t synchronize their internal clock to the 24-hour light-dark cycle. It occurs in over half of blind people, rarely in sighted people.

Hetlioz increases nighttime sleep in blind patients about same as melatonin (28 minutes) at a cost of $10,000/MONTH. Hetlioz is NOT  for sighted or blind patients who don’t have non-24


Diphenhydramine (Benadryl®) , Tylenol PM®, Nytol®, Sominex®, Simply Sleep®

Contain 25mg of diphenhydramine as an OTC sleep aid.

Dose 50mg mg at bedtime. (generally, 25mg is adequate)

Side effects: drowsiness, anticholinergic side effects, avoid in older males.

Evidence: There is little evidence that diphenhydramine improves insomnia.  Will also cause daytime sedation the next day. Use of diphenhydramine to treat insomnia is not recommended, especially for long term use.

Drugs for sleep maintenance:

Tricyclic Antidepressant

Doxepin (Silenor)

USE: Very low dose anti-depressant that is used for insomnia.  It increases sleep time by 30 minutes and is most useful for patients having trouble staying asleep.  Doesn’t help with sleep INDUCTION, just maintenance. Prescribing low dose doxepin (10mg) is a cheaper alternative than using Silenor or it’s expensive generic.  The generic Silenor currently costs $400 for 30 tablets.

Orexin receptor antagonist

BELSOMRA (suvorexant)

Start with 10mg, may increase to a max of 20mg if tolerated. Start with 5mg if CYP450-3A4 blocking drug.

Indication: for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance 

Mechanism:  is a highly selective antagonist for orexin receptors. Orexin is a neurotransmitter found in a specific part of the brain that can help keep a person awake. This drug blocks hormones that keep us awake.

Precautions: “Sleep driving” and other complex behaviors (preparing and eating food, making phone calls, or having sex), with amnesia for the event have been reported with the use of hypnotics.

ADVICE from your Thompson Pharmacist:

Your Thompson Pharmacist is a great resource in helping you get a better night sleep. Before your physician prescribes any medications, be sure you are doing all you can to get a restful night’s sleep. It is important for you to practice good sleep hygiene:

  • regular waking time (set alarm!) including weekends.
  • go to bed only when sleepy. Avoid trying to “force sleep”
  • avoid daytime naps
  • exercise, but not within 1 hour of bedtime
  • sleep in a cool room (avoid temperature extremes)
  • avoid alcohol and stimulants before bedtime. (including chocolate & coffee, soda, etc)
  • avoid stressful arguments
  • bedroom is for sleeping and sex
  • NO TV, computers, or reading.  AVOID GRAY SCREENS!
  • Schedule “worry time” during the day. Do not take your troubles to bed.
  • Avoid excess fluids in the evening, to avoid restroom trips.
  • Do something relaxing and enjoyable before bed.

Feel free to ask your Thompson Pharmacist for advice in helping you get a better night sleep.  Go Ahead and AS… at Thompson Pharmacy it’s ALL FOR YOU!