Transcript Treatment for Insomnia

Treatment for Insomnia
Presentation By: JJ Wojcik
Presentation Outline
What is Insomnia?
Treatment of Insomnia
Non-Pharmacological
Pharmacological
Benzodiazepines
Benzodiazepine Receptor Agonists
Melatonin-Receptor Agonists
Anti-Depressants
Future Treatments
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
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
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
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
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
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 is
typically said to be comorbid insomnia
Causes of Insomnia
Often caused by depression or other
psychiatric problems
Also caused by excess, lasting stress
or racing thoughts at bedtime
Symptoms of insomnia also could
be cause by other sleeping disorders
such as:
Restless Leg Syndrome
Sleep Apnea
Somnolence
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 don’t routinely ask about it
Patients don’t think it’s important enough to bring up
in a normal check up
Goes overlooked
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
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 improve sleep
habits
The different methods used are:
Improving Sleep Hygiene
Stimulus Control Therapy
Restrictive Sleep Therapy
Improving Sleep Hygiene
Basically improving comfort when sleeping
Decrease Ambient Noise
Go to bed/wake up at a constant time
Reduce Lighting
Think 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
Stimulus Control Therapy
Learn to associate the bedroom with sleep alone
Don’t go in the bedroom unless going to sleep
Do not go to bed unless tired
Leave the bedroom if haven’t fallen asleep in 15
minutes
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
Sleep Restriction Therapy
Restricting sleep during the day
Cutting sleep short during certain nights
Goal is to be excessively tired when time to sleep at
night
Shown the most promising results of all the nonpharmacological therapies and even more effective
when sleep hygiene is improved
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
Benzodiazepines
More than 45 years old and are potent hypnotics and anxolytics
Improve sleep time, but not usually sleep latency (often one 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 as well as
tolerance
Drugs in this class are
Estazolam, Flurazepam, Quazepam, Temazepam, and Triazolam
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, and
inducing sleep is therefore achieved
Improves sleep onset, but not necessarily sleep
maintenance
Bad reported rebound insomnia with discontinued use
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 proportional the
dose
Clearance and time for elimination are not dose
dependent
Other Benzodiazpeines
Flurazepam
Quazepam
Temezepam
Benzodiazepine Receptor Agonists
Fewer 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 sleep maintenance
Some drugs are dose dependent (Eszopiclone)
Few are approved for long-term use: Eszopiclone
Drugs in the class include:
Zolpidem, Zaleplon, and Eszopiclone
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
Effectiveness of the drug is dose dependent
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 dose
dependent in the patients examined
CYP 3A4 and 2E1 were involved in the metabolism of
the drug
Mean elimination time was 5.8 hours
Melatonin Receptor Agonists
Newer 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
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
Pharmacokinetics
Undergoes extensive first pass metabolism
Half-life ranged from 1-3 hours
All pharmacokinetic properties have been seen to be
dose proportional
Antidepressants/Antipsychotics
Some physicians prefer this mode of treatment over
benzodiazepines because of the far less potential for
dependency
Can produce anticholinergic effects if used too long:
Constipation
Weight Gain
This is mostly used in patients who suffer from
comorbid insomnia as a result from depression
Non-Prescription Supplements
There are certain different non-prescription
supplements that are also used an thought to be
effective
These include:
Antihistamines
Melatonin
Valerian
Antihistamines
Used because many people will experience sleep
inducing side effects from this kind of medicine
Typically in patients with acute insomnia who need a
“quick fix” for a restless night here and there
Tolerance can and most often will be gained if used too
much
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
Valerian
This is an herb that is thought to interact at the
GABAA receptor because of it’s 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 FDA’s Generally Recognized as Safe
List
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
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.
Homework Question
Explain the mechanismm of action of the
benzodiazepam class of hypnotic agent.
References
Sullivan, Shannon S.; Guilleminault, Christian. Emerging drugs for insomnia :
new frontiers for old and novel targets. Expert Opinion on Emerging Drugs
(2009), 14(3), 411-422
Passarella, Stacy; Duong, Minh-Tri. Diagnosis and treatment of insomnia.
American Journal of Health-System Pharmacy (2008), 65(10), 927-934
Hair, Philip I.; McCormack, Paul L.; Curran, Monique P. Eszopiclone : a review 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 after abrupt discontinuation of
hypnotic treatment: Double-blind randomized comparison of zolpidem versus
triazolam. Human Psychopharmacology (1996), 11(3), 225-233
Nguyen, Nancy N.; Yu, Susan S.; Song, Jessica C. Ramelteon : a novel melatonin
receptor agonist for the treatment of insomnia. Formulary (2005), 40(5), 146-150,
152-155