Insomnia_2010a.ppt

7/29/2019 Insomnia_2010a.ppt

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Treatment for InsomniaPresentation By: JJ Wojcik


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Presentation Outline

What is Insomnia?

Treatment of Insomnia

Non-Pharmacological

Pharmacological

Benzodiazepines

Benzodiazepine Receptor Agonists

Melatonin-Receptor Agonists

Anti-Depressants

Future Treatments


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What is Insomnia?

Classified as the inability to get enough sleep

despite adequate time.

Symptoms Include:

Delayed Sleep Onset

Early Morning Wake-Ups

Unrefreshing Sleep

Trouble Maintaining Sleep

Causes many problems in daytime functioning


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Classifications of Insomnia

Primary vs. Secondary

This is based on what is causing a patient to

suffer from lack of sleep

Chronic vs. Acute

This is based on how long the patient suffers from

symptoms of insomnia


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Primary Insomnia

Also referred to as Idiopathic

This is diagnosed when a patient has no other

cause of insomnia other than the fact they cannot

sleep

Also been known to be patient confusion and

misconception around what is meant and

understood to be sleep


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Secondary Insomnia

This is also more commonly referred to as

Comorbid Insomnia

When insomnia is being caused by some other

outside factor, illness, or disorder including:

Drug Abuse

Psychiatric Disorders

Medical Problems

Other Sleep Disorders disruptive to sleep


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Acute Insomnia

This is when a patient suffers from insomnia

fewer than 3 times a week for less than a month

Typically stems from changes in the environment

and a short illness the patient might have had


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Chronic Insomnia

This will be diagnosed when a patient suffers

from symptoms more than 3 times a week for a

period longer than a month

When insomnia becomes a chronic problem, it istypically said to be comorbid insomnia


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Causes of Insomnia

Often caused by depression or

other psychiatric problems

Also caused by excess, lasting

stress or racing thoughts atbedtime

Symptoms of insomnia also

could be cause by othersleeping disorders such as:

Restless Leg Syndrome

Sleep Apnea

Somnolence


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Diagnosing Insomnia

The diagnosis of insomnia can often be difficult

and is a prolonged process

Sleep logs

Watching symptoms for weeks at a time

It is often very underdiagnosed due to both

patient and physician misunderstandings

Doctors dont routinely ask about it

Patients dont think its important enough to bring

up in a normal check up

Goes overlooked


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Treatment of Insomnia

Insomnia is not a disorder that can necessarily

be cured

Symptoms treated in order to relieve patient of

distress

Treated by two different methods

Non-Pharmacological Treatment

Pharmacological Treatment


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Non-Pharmacological

Treatment

This is attempted before the use of

pharmacological treatment, typically for at least

2-3 weeks

This mainly has to do with attempting to improvesleep habits

The different methods used are:

Improving Sleep HygieneStimulus Control Therapy

Restrictive Sleep Therapy


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Improving Sleep Hygiene

Basically improving comfort when sleeping

Decrease Ambient Noise

Go to bed/wake up at a constant time

Reduce LightingThink Positively

Not shown to be particularly effective on its own,

though has been seen to be very critical to

improving the efficacy of other non-

pharmacological treatments


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Stimulus Control Therapy

Learn to associate the bedroom with sleep alone

Dont go in the bedroom unless going to sleep

Do not go to bed unless tired

Leave the bedroom if havent fallen asleep in 15minutes

Be completely relaxed when in bed

This method has been seen to be very effective if

used for over a prolonged period of time

Improved efficacy if sleep hygiene is also

managed


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Sleep Restriction Therapy

Restricting sleep during the day

Cutting sleep short during certain nights

Goal is to be excessively tired when time to sleepat night

Shown the most promising results of all the non-

pharmacological therapies and even more

effective when sleep hygiene is improved


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Pharmacological Treatment

This is the treatment of insomnia with the use of

pharmacological agents

Most often prescription agents

Some supplements used

4 Classes of Prescription Agents

Benzodiazepines

Benzodiazepine Receptor Agonists

Melatonin Receptor Agonists

Antidepressants/Antipsychotics

Some supplements are thought to help as well


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Benzodiazepines

More than 45 years old and are potent hypnotics andanxolytics

Improve sleep time, but not usually sleep latency (oftenone of the more desired effects)

Disrupt normal sleep cycles

Tend to cause bad hangover effects

Very drowsy the following day

Occasional impaired cognition

Extremely high potential for abuse with prolonged use aswell as tolerance

Drugs in this class are

Estazolam, Flurazepam, Quazepam, Temazepam, andTriazolam


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Triazolam Mechanism

Interacts with the GABAA receptor to bind at the

post synaptic membrane and induce chloride

permeability to inhibit excitation

By doing so, hypnotic effects are induced, andinducing sleep is therefore achieved

Improves sleep onset, but not necessarily sleep

maintenance

Bad reported rebound insomnia with

discontinued use


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Pharmacokinetics

This has a very short half-life, as many of the

other benzodiazepines, staying in the system

about 2-5 hours

The amount in the system (AUC) is proportionalthe dose

Clearance and time for elimination are not dose

dependent


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Other Benzodiazpeines

Flurazepam

Quazepam

Temezepam


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Benzodiazepine Receptor

AgonistsFewer hangover symptoms than benzodiazepines

Claim amore restful night sleep

Fewer problems with dependency, though still an issue

Do not show deleterious effects to the sleep cycle

Longer half-life than benzodiazepines so help with sleepmaintenance

Some drugs are dose dependent (Eszopiclone)

Few are approved for long-term use: Eszopiclone

Drugs in the class include:

Zolpidem, Zaleplon, and Eszopiclone


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Eszopiclone (Lunesta)

Mechanism

Binds at the omega subunit of the

GABAA receptor to increase chloride

permeability and decrease excitation

of the neuron

This subunit is found more in the brain

as opposed to the spine where the

other class of the GABA receptors are

found

Thought to be safer than

benzodiazepines, but still have serious

potential for abuse, and reported

rebound insomnia with discontinued

use


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Pharmacokinetics

This drug does have a relatively fast half-life and

elimination time but can be delayed after a high

fat meal

Both the AUC and the Cmax were seen to be dosedependent in the patients examined

CYP 3A4 and 2E1 were involved in the

metabolism of the drug

Mean elimination time was 5.8 hours


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Melatonin Receptor

AgonistsNewer class of drug

Far less potential for abuse and dependency and is

the only hypnotic that is not classified as a controlled

substance

Approved for long-term use more readily than other

medications

There have been complains of drowsiness, dizziness,and fatigue in the following days after use

Only drug in this class thus far is Ramelteon


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Ramelteon Mechanism

This works by selectively binds the Melatonin

Receptors (MT)1 and MT2, that are thought to

regulate the sleepiness and readjustment of the

circadian rhythms, respectively

Does not show any addictive or dependency in

patients because it does not, nor do any of its

metabolites, bind to any large ligand group

receptors


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Pharmacokinetics

Undergoes extensive first pass metabolism

Half-life ranged from 1-3 hours

All pharmacokinetic properties have been seento be dose proportional


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Antidepressants/Antipsychot

icsSome physicians prefer this mode of treatment

over benzodiazepines because of the far less

potential for dependency

Can produce anticholinergic effects if used toolong:

Constipation

Weight Gain

This is mostly used in patients who suffer from

comorbid insomnia as a result from depression


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Non-Prescription

SupplementsThere are certain different non-prescription

supplements that are also used an thought to be

effective

These include:

Antihistamines

Melatonin

Valerian


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Antihistamines

Used because many people will experience

sleep inducing side effects from this kind of

medicine

Typically in patients with acute insomnia whoneed a quick fix for a restless night here and

there

Tolerance can and most often will be gained if

used too much


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Melatonin

Naturally produced hormone in the pineal gland

This hormone keeps the circadian rhythm

There has not been a minimum dose established

Not shown to be necessarily effective


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Valerian

This is an herb that is thought to interact at the

GABAAreceptor because of its sedative

properties similar to other drugs that act at that

receptor

Can cause some nausea, upset stomach,

dizziness, and long-lasting fatigue

Is included on the FDAs Generally Recognized

as Safe List


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Future Treatments

Most future treatments have to do with other

stimulations of the GABA receptor

Some facing problems for their problems in pregnant

women and their abuse/dependency issues

There are also trials being done to assess the

efficacy of the 5-HT receptor in treating insomnia

Different agonists have shown to improve sleep onset

and sleep maintenance

Many other Melatonin Receptor Agonists are also

being researched to go alongside Ramelteon in this

class of drug


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Assigned Reading

Monti, Jaime M. Primary and secondary

insomnia: Prevalence, causes and current

therapeutics. Current Medicinal Chemistry:

Central Nervous System Agents (2004), 4(2),

127-134.


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Homework Question

Explain the mechanismm of action of the

benzodiazepam class of hypnotic agent.


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References

Sullivan, Shannon S.; Guilleminault, Christian. Emerging drugs forinsomnia : new frontiers for old and novel targets. Expert Opinionon Emerging Drugs (2009), 14(3), 411-422

Passarella, Stacy; Duong, Minh-Tri. Diagnosis and treatment ofinsomnia. American Journal of Health-System Pharmacy (2008),65(10), 927-934

Hair, Philip I.; McCormack, Paul L.; Curran, Monique P. Eszopiclone : areview of its use in the treatment of insomnia. Drugs (2008), 68(10),1415-1434

Silvestri, R.; Ferrillo, F.; Murri, L.; Massetani, R.; Perri, R. Di; Rosadini, G.;Montesano, A.; Borghi, C.; Giclais, B. De La. Rebound insomnia afterabrupt discontinuation of hypnotic treatment: Double-blind randomized

comparison of zolpidem versus triazolam. HumanPsychopharmacology (1996), 11(3), 225-233

Nguyen, Nancy N.; Yu, Susan S.; Song, Jessica C. Ramelteon : a novelmelatonin receptor agonist for the treatment of insomnia. Formulary(2005), 40(5), 146-150, 152-155

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