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Insomnia 2010a
Insomnia 2010a
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
Classifications of Insomnia
Primary vs. Secondary
This is based on what is causing a patient to suffer from lack of sleep
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
Treatment of Insomnia
Insomnia is not a disorder that can necessarily be cured
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
Not shown to be particularly effective on its own, though has been seen to be very critical to improving the efficacy of other nonpharmacological treatments
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
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
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
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
Other Benzodiazpeines
Flurazepam
Quazepam
Temezepam
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
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/Antipsychot ics
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 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
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