Drugs for Sleep & Awake

The good and the bad

 Lawrence Martin

Lawrence Martin, M.D., FACP, FCCP

Associate Clinical Professor of Medicine
Case Western Reserve University School of Medicine, Cleveland
Board Certified in Pulmonary and Sleep Medicine

Sleep Home Page | Internet Sleep Links | Books about sleep disorders (with links to Amazon.com) | Return to Lakeside Press

1  
1.  Drugs for sleep:  to obtain sleep or stay asleep
a.  Over the counter (no prescription needed)
b. Prescription only and FDA-approved for insomnia
c.  Prescription only and not FDA-approved for insomnia

2.  Drugs for staying awake
a.  Over the counter (no prescription needed)
b.  Prescription only and FDA-approved for staying awake

1. DRUGS FOR SLEEP

a. Over the counter (no prescription needed)

ALCOHOL

GOOD:  Initially induces sleep by decreasing sleep latency.  Increases deep sleep and increases sleep continuity

BAD: As alcohol level declines (within hours), sleep becomes interrupted and deep sleep is reduced. The result: NOT a good night's sleep. Also, alcohol relaxes throat muscles and thereby increases tendency to snore and develop obstructive sleep apnea.

  ANTI-HISTAMINES:  1st generation H1 receptor antagonists

  • Diphenhyramine (Benadryl, Nytol, Sominex, Tylenol PM)

  • Doxylamine (NyQuil; Unisom)

  • Nyquil

GOOD: Anti-histamines do cause drowsiness, and are especially helpful if allergic symptoms make it difficult to sleep. They are not addicting.

BAD:  Tolerance quickly develops and they are NOT good for long term treatment of insomnia.  They also have potent anti-cholinergic side effects, which may lead to ataxia (loss of balance), dry mouth and throat, flushed skin, tachycardia, photophobia, urinary retention, constipation.  Especially in the elderly, they may cause difficulty concentrating, short term memory loss, hallucinations, confusion, erectile dysfunction, and delirium.  Many nursing homes ban use of these drugs for sleep.   Finally, diphenhydramine has been abused for recreational use (at 4-20 times regular dose).

MELATONIN

GOOD:    Melatonin is a natural hormone from pineal gland (sits beneath the brain); it is normally secreted at night.  Melatonin has sleep- promoting properties.  Appears to be most effective when given 1 to 3 hours before bedtime.  Typical doses are 0.3-5.0 mg.  The drug is also commonly used to treat "jet lag syndrome."

BAD:  There is great individual variability in response.  Because there are many studies with highly variable & conflicting results, the FDA has never approved melatonin for anything.  Also, as an over the counter drug its purity is not guaranteed and what you buy may or many not have the amount of melatonin advertised on the label.

Other OTC agents

These include catnip, valerian, and tryptophan. There are a lot of myths and misconceptions about these OTC agents.  Catnip is from the flowering plant Nepeta, and has long been observed to effect the behavior of cats; some OTC products for humans contain it as well.  Valerian is another flowering plant that has some sedative qualities.  Tryptophan is a normal human amino acid that is found in turkey meat, thought by many to induce sleep.  A good place to start learning about OTC agents is the Wikipedia articles they link to.  See also:

Catnip: Past and Present
"Valerian", review in American Family Physician
 Does Eating Turkey Make You Sleep? Tryptophan & Carbohydrate Chemistry

1. DRUGS FOR SLEEP

b. Prescription only and FDA-approved for insomnia

Benzodiazepines ("benzos")

Main clinical use of this class is to treat anxiety.  Several "benzos" are FDA-approved for treating insomnia, including:

DRUG (brand name) Bedtime Dose Drug half-life (hours)
Triazolam (Halcion) 0.125 - 0.25 mg 2-6 (short; gone by morning)
Temazepam (Restoril) 15 - 30 mg 8-25 hours (may have next day effect)
Flurazepam (Dalmane) 15-30 mg 70-90 hours (next day effects common)

GOOD:  The fact that Benzos are FDA-approved indicates appropriate studies have been done showing their efficacy for insomnia.  As a group, benzodiazepines have a much better safety profile than the older barbiturates or tricyclic antidepressants, drugs that in the past were widely used for insomnia (but were not FDA-approved for this purpose).  In contrast to the older drugs, overdoses of benzos are almost never fatal.  Also good is that these drugs are now generic and relatively inexpensive compared with the newer 'Z' drugs discussed below.

BAD:  There are several potential adverse effects, including:

  • Next-day sedation with impairment of cognitive (thinking) function. 

  • 'Anterograde amnesia', or memory failure for information presented after taking drug.  (This is seen with all 'hypnotics'.)

  • DISCONTINUATION EFFECTS - problems when the drug is stopped include a) rebound insomnia, especially after high doses.  This tends to be brief, lasting 1-2 nights; b)recurrent insomnia (same problem with sleeping as before drug was taken; c) withdrawal – appearance of new symptoms, lasts >1-2 nights

    "Z" drugs

    These are drugs that work on the same brain receptors as benzos, but have a different type of structure.  They are called "benzodiazepine receptor agonists with non-benzodiazepine structure", or "Z" drugs for short.  Insomnia is the only approved indication for these drugs.  They include:

     GOOD:  They are FDA-approved for insomnia.  Serious side effects are rare and there is less risk of dependency than with benzodiazepines.   They are approved for long term use.

     BAD:   Only Ambien is generic (Ambien-CR is a brand name for slow release ambien, and is not generic).  The other Z drugs are more expensive than generic ambien.  Side effects:  next day drowsiness; anterograde amnesia; rebound insomnia (less than with benzos).  There is an FDA warning of (rare) risk of parasomnias (e.g., somnambulism or sleep walking; sleep-related eating disorder).

        Ramelteon (Rozerem)

    Ramelteon (Rozerem) is FDA-approved only for sleep-onset insomnia  (not for sleep maintenance).  

    GOOD:  Rozerem is a melatonin-receptor agonist, which means it acts on melatonin brain receptors and mimics the body's natural hormone melatonin.  Unlike all other prescription drugs for sleep, it does not have addiction potential; as such, it is the only non-scheduled prescription drug for insomnia in U.S. (this means it is not a controlled drug, and doctors don't have to use their controlled-drug number as when prescribing the other drugs for sleep).  It comes in only one dose - 8 mg per tablet, taken before bedtime.  There is no limitation on length of use (same is true of Ambien CR and Lunesta; all other insomnia drugs have time limitation).

    BAD:   For some people it is less effective than benzos and the Z drugs.  And, like all brand name prescription drugs for sleep, Rozerem is relatively expensive compared to generic ambien.

1. DRUGS FOR SLEEP

c. Prescription only- Not FDA approved but widely used for treating insomnia

DRUG (brand name) Dose at bedtime FDA-approved for:
Trazodone (Desyrel) 50 - 100 mg depression
Mmirtazapine(Remeron) 15 - 30 mg depression
Amitryiptyline (Elavil) 25 - 50 mg depression
Quetiapine (Seroquel) 25 - 100 mg psychosis
Clonazepam (Klonopin) 0.5 - 2.0 mg panic disorder
2.  DRUGS FOR STAYING AWAKE

a. Over the counter (no prescription needed)

CAFFEINE

  • Active ingredient in coffee
  • History of coffee dates to 9th century
  • 1652 – First coffee house in London
  • 1819 - Caffeine officially discovered as wake-promoting agent in coffee & tea
  • Main mechanism is to block A1 adenosine receptors in the brain, thereby inhibiting sleep onset and maintenance.
  • Usual caffeine dose in tablet form is 50-200 mg. NoDoz regular strength = 100 mg caffeine, maximum strength = 200 mg. Grande Starbucks coffee = 550 mg. Can of Diet Coke = 46.5 mg. Can of Sprite has zero mg caffeine.


 
Starbucks coffee size mg caffeine
Grande 550
Short 250
Tall 375
Tall Decaf 10
 

GOOD about Coffee:

ÜMakes you feel more alert
ÜIncreased capacity for physical & mental work
BAD about Coffee:
Üside effects including nervousness, irritability, anxiety, tremulousness, insomnia, headaches, palpitations, esophagitis, GI reflux
2.  DRUGS FOR STAYING AWAKE

b.  Prescription only and FDA-approved for staying awake

 

GOOD & BAD

The older group of 'stay awake' drugs - amphetamines - has been around for decades, and has many downsides: very high abuse potential, side effects of irritability and palpitations. Because of abuse, they are FDA Schedule II, which means they are much more tightly controlled than the insomnia drugs (benzos and Z drugs), which are Schedule IV.  They are still widely prescribed, but not routinely as stay awake medications. Ritalin (methylphenidate) is indicated for attention deficit disorder, and is also sometimes used for treating sleepiness in narcoleptic patients.

The newer drugs were developed mainly to treat the sleepiness of narcolepsy. The first of these, modafinil (Provigil), was released in 1998 specifically for narcolepsy. More recently, it has been FDA-approved for sleepiness in shift workers and in patients with sleep apnea who are using their CPAP machines but are still sleepy during the day. However, the drug is widely used 'off label' to treat many patients who are just 'sleepy' when they shouldn't be. A cousin of this drug, Nuvigil, was released in 2007 but is not widely promoted or used. 

Side effects of mondafinil are usually not serious.  The main side effect is headache.  Less common side effects include dry mouth, anorexia, nausea and diarrhea.

Xyrem is specifically approved only for narcolepsy, and is not used off label.  It is tightly controlled, and is distributed from only a single source in the U.S.  The drug is cumbersome to take, in that it requires a bed time dose and then ANOTHER DOSE about 4 hours later - the patient is supposed to wake up and take the second dose. However, it is an excellent drug to treat the 'cataplexy' of narcolepsy, and also to promote day time alertness in this group of patients. 

Sleep Home Page | Internet Sleep Links | Books about sleep disorders | Return to Lakeside Press
Forward any comments to:
larry.martin@roadrunner.com

Copyright © 2009, Lawrence Martin, M.D.