Sleep Disorders

Medicines for Insomnia

When sleep disturbances are not resolved with other supportive care measures, the use of sleep medications may be helpful. These medicines are almost always prescribed only for short times. Prolonged use of sleep medications for persistent insomnia can impair natural sleep patterns (i.e., rapid eye movement deprivation) and alter physiologic functions. Prolonged use (more than 1 to 2 weeks) of these medications can result in tolerance, psychological and physical dependence, drug intoxication, and drug hangover. More tips on taking sleeping aids.

Insomnia is an issue for many people, and there are many different ways to attack the problem, such as through exercise and changing the patient’s sleeping patterns. Another option for management is via pharmaceuticals, both over-the-counter (OTC) and prescription. OTC medications tend to be used for infrequent and/or mild cases of insomnia, whereas prescription drugs are usually used for chronic and moderate-to-severe situations.

A new drug, Lunesta (Eszopiclone) has been approved recently by the FDA for more prolonged use. The regulatory authorities apparently felt it was more targeted than older drugs and could be tolerated better without becoming habit forming. There were clinical trials to back up this assessment, but the real test will be in large scale use, which will start now that the drug has gone on the market

The action of sleep medication in the brain

The cells in the brain are called neurons. Usually they are at rest and do not communicate with other neurons.

Almost all sleep aids exert effects on neurotransmitters, either by affecting the breakdown, reuptake, or binding to a cell receptor (antagonists). Antihistimines block the effects of a neurotransmitter on the postsynaptic receptor. Benzodiazepines are agonists and stimulate the postsynaptic receptor.

The effects can be complex, but the neurotransmitters either make the postsynaptic neuron more likes to fire (excitatory) or less likely to fire (inhibitory).

Benzodiazepines

Benzodiazepines were developed as anti-anxiety drugs. The main beznodiazepine in the 60’s was Valium, which was the top selling prescription drug in the country for several years. These medicines enhance the activity of the inhibitory neurotransmitter GABA. Because they effectively permit people who take them to get to sleep, they found use as sleeping pills. Benzodiazepines with short half-lives were developed to produce sleeping pills that did not leave the user with a sedated hang-over the next morning.

diazepam (Valium)
temazepam (Restoril)
triazolam (Halcion)
clonazepam (Klonopin)

flurazepam (Dalmane)

clonazepam (Klonopin)

quazepam (Doral)

triazolam (Halcion)

lorazepam (Ativan)

alprazolam (Xanax)

estazolam (ProSom)

flunitrazepam (Rohypnol)

temazepam (Restoril)

oxazepam (Serax)

prazepam (Centrax)

Tricyclic antidepressants

At one time, tricyclic antidepressants were the go-to prescription for doctors when patients complained about insomnia. The off-label, first-line use of antidepressants for treating insomnia in the absence of depression is now considered debatable. (Nonbenzondiazepone drugs are now the most common.)

doxepin (Sinequan)
amitriptyline (Elavil)
nortriptyline (Pamelor)

Chloral derivatives

chloral hydrate

Antihistamines

diphenhydramine (Benadryl)
hydroxyzine (Vistaril, Atarax)

Other

zolpidem tartrate (Ambien)
zaleplon (Sonata)

Lunesta

Valerian

Anxiolytic and Sedative-Hypnotic Drugs

Sedatives and hypnotic drugs are prescribed to produce drowsiness and to promote sleep

Sedatives -- drugs that decrease activity and moderate excitement;
Hypnotics -- drugs produce drowsiness and facilitate the onset and maintenance of sleep, from which one is easily aroused – hypnosis

Many drugs that are anxiolytic and sedative-hypnotic alter the continuum of excitability in the person. At low doses, many patients have a greater sense of well-being and decreased arousal. At higher doses, people become sleepy and their cognitive physical performance deteriorates.

An anxiolytic is any drug or therapy used in the treatment of anxiety disorders that works on the central nervous system to relieve the symptoms of anxiety. Anxiolytics are not “minor tranquilizers".

Sleep experts recognize that both primary and secondary sleep disorders often result in people using prescription and non-prescription drug use that may as a side effect exacerbate disturbances in sleep.

Morphine and similar opioid drugs cause selective decreases in rapid-eye-movement (REM) sleep through actions on brainstem cholinergic neurons, neurons known to participate in the initiation of this sleep state.

In recent years, neuroscience research has provided new insights into the complex circuitry, neurotransmitters and neuromodulatory substances involved in sleep/wake regulation. We also know somewhat more about the functioning of brain circuits involved in circadian rhythm control. Because of these findings, greater opportunity exists to better understand the actions of drugs on the brain, and also to investigate novel classes of drugs that have non-traditional mechanisms of action on receptor systems within these newly refined brain circuits. It is an exciting time for insomnia medication.

Definitions of Drug Actions

Agonists: drug compounds that bind to and cause a functional effect identical in quality and quantity to the endogenous ligand

Antagonist: drug compounds that bind but cause no functional effect;

Partial Agonist: causes functional effect that, at a maximum, is only a fraction of that of the endogenous ligand

Intrinsic activity – efficacy relative to endogenous ligand (% of activity in relation to 100% for endogenous ligand)
Intrinsic efficacy – is the intrinsic characteristic of the drug

Many medicines work because the body’s cells have receptors that interact with the drug molecules. An agonist is a drug that mimics the affect of a natural chemical in the body by binding to the receptor that the natural chemical occupies. An antagonist is a drug that blocks the natural chemical. You hear many drugs described as such-and-such agonists or antagonists. For instance, the headache medicine Imitrex is a serotonin agonist.

Narcotics

Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia.

Alcohol and Sleep

New Finding about Alcohol and Sleep

New research shows that Americans are taking more sleeping medications than ever.

Sleep Aids for Seniors

Challenges of treating seniors with sleep problems

Scientists working on sleep/wake equation