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Medications for Insomnia: A Story of Risks and Benefits

Medications for Insomnia: A Story of Risks and Benefits. Sarah M. Richey, MD September 3 rd , 2008. Objectives. Be able to define insomnia Describe why a doctor would recommend treatment for insomnia Identify the two types of treatment for insomnia

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Medications for Insomnia: A Story of Risks and Benefits

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  1. Medications for Insomnia:A Story of Risks and Benefits Sarah M. Richey, MD September 3rd, 2008

  2. Objectives • Be able to define insomnia • Describe why a doctor would recommend treatment for insomnia • Identify the two types of treatment for insomnia • Understand what a risk/benefit analysis is and how physicians use it when prescribing meds for insomnia

  3. What is insomnia? • Persistent difficulty initiating or maintaining sleep • Do not wake feeling refreshed • Decline in social or occupational functioning

  4. Prevalence • 10-20% of the general population • 50% of those seen in primary care clinics • Most common sleep disorder

  5. Insomnia’s Effects • Daytime sleepiness • Fatigue • Cognitive impairment • Decline in work performance • Work days missed • Depression and Anxiety

  6. The Risk/Benefit Analysis • Doctors make most of their medical treatment decisions based on this principle • Risks of not treating the patient are weighed against the expected benefits and risks of each treatment

  7. The Balancing Act • It is only because there is some loss of function or quality of life that there is something to be gained by starting therapy that will have costs and risks. • Those with greater impairment will stand to gain greater benefit from treatment.

  8. What does the evidence say? • The choice of treatment is guided by which treatment is associated with the greatest ratio of benefits to cost/risks. • Doctors get this information from well-designed research studies that included subjects similar to their patient

  9. Insomnia Therapies • Pharmacologic • Non-pharmacologic • Both have strong evidence to support their use

  10. The Non-pharmacologic Approach • Cognitive Behavioral Therapy for Insomnia (CBTi) • Stimulus control therapy • Sleep restriction therapy • Relaxation training • Cognitive therapy • Sleep hygiene education

  11. The Pluses of CBTi • Benefits are long-lasting, even after therapy is over • Relatively free of medical risks • No significant interactions with other medical treatments

  12. And the minuses… • Monetary cost (repeated visits to a provider) • Improvement may not occur for several weeks • Requires time and motivation • Daytime sleepiness during sleep restriction • Lack of access to a trained therapist • Lack of therapist expertise

  13. Combined Treatment • CBTi can be used along with medications. • For example, medications can provide rapid relief and CBTi can lead to long-lasting results.

  14. Pharmacologic Therapies • Benzodiazepines • Non-benzodiazepine hypnotics • Melatonin receptor agonists • Antidepressants • Antipsychotics • Antihistamines

  15. Benzodiazepines • Many end in “pam” or “lam” • clonazepam (Klonopin) • lorazepam (Ativan) • diazepam (Valium) • alprazolam (Xanax) • temazepam (Restoril) • triazolam (Halcion)

  16. GABA receptor

  17. The Good Side of Benzos • Enhance sleep • Decrease anxiety • Muscle relaxant

  18. The Bad Side of Benzos • Daytime sedation • Decreased reaction time • Unsteadiness of gait—can lead to falls • Cognitive impairment & memory problems • Risk of tolerance • Risk of withdrawal (and rebound insomnia) • Risk of abuse

  19. Non-benzodiazepine hypnotics • Examples: • zolpidem (Ambien) • zolpidem ER (Ambien CR) • zaleplon (Sonata) • eszopiclone (Lunesta)

  20. The Pluses • Bind to sub-types of GABA receptors that specifically modulate sleep and therefore are thought to have less unwanted side effects • Tolerance and abuse have not been shown to be a major problem in the general population • In general have shorter duration of action than most benzos and therefore are less likely to cause next day sedation

  21. The Minuses • But drowsiness, dizziness, unsteadiness of gait, rebound insomnia and memory impairment have been reported.

  22. FDA Indications • Sleep onset only: zolpidem and zaleplon • Sleep onset and sleep maintenance: zolpidem ER and eszopiclone

  23. Ramelteon • Brand name is Rozerem • Selective agonist at MT1 and MT2 melatonin receptors • FDA approved for sleep-onset insomnia • Only medication FDA approved for insomnia that is not a controlled substance because it does not seem to lead to abuse or withdrawal • Associated with headache, dizziness, drowsiness, fatigue and nausea

  24. Antidepressants • Commonly used for insomnia but are not FDA approved • trazodone • doxepin • amitriptyline • mirtazapine

  25. Trazodone • Used at much lower doses for insomnia than depression • The most commonly prescribed agent for treating insomnia across all classes of medications • No good research to support its use • Major side effects: sedation, dizziness, dry mouth, orthostatic hypotension, priapism (rare)

  26. The Tricyclics • amitriptyline (Elavil) • doxepin (Sinequan) • Side effects: dry mouth, urinary retention, dizziness, daytime sedation • Used at much lower doses for insomnia than depression

  27. Mirtazapine • Brand name: Remeron • Associated with weight gain, increased appetite, daytime sedation and dizziness

  28. Antipsychotics • Called the “atypical antipsychotics” • Block dopamine from binding to receptors in the brain • Examples: • risperidone (Risperdal) • olanzapine (Zyprexa) • quetiapine (Seroquel) • ziprasidone (Geodon)

  29. Antipsychotics • Not FDA approved for insomnia • Typically used at doses much lower than those for treating psychosis • Quite sedating but also associated with weight gain, increased risk for diabetes, high blood pressure, restless leg syndrome, muscle spasm or parkinson-like symptoms • Quetiapine and ziprasidone have been shown to increase total sleep time as well as sleep efficiency

  30. Antihistamines • Diphenhydramine (Benadryl, Tylenol PM) and Doxylamine (Unisom), hydroxyzine (Vistaril) • Little evidence to support their use • Side effects: dry mouth, urinary retention, blurred vision, dizziness, sedation

  31. Caution with the “PM” meds! • They all have more than one medication in them. • Taking too much Tylenol is dangerous! • May interact with other medications patients are taking, and doctors may not think to ask if their patients are taking them. • Patients should always tell their doctors they are taking these meds.

  32. Another Caution: Mixing Pills Heath Ledger had insomnia and passed away from an accidental overdose of the following medications: oxycodone hydrocodone diazepam temazepam alprazolam doxylamine

  33. Take Home Points • Insomnia is defined by having daytime symptoms. • There are two pathways for treating insomnia: medications and CBTi. They can be used at the same time. • All treatments have their pluses and their minuses. Doctors look at the patient’s impairment and weigh that against the risk of treatment.

  34. Take Home Points • Many of the most common drugs for insomnia are not FDA approved for that purpose. • No drug for insomnia is completely safe or free of the risk of side effects. • Be sure to inform your doctor of all medications you are taking, including over-the-counter and herbal ones.

  35. References • Cohrs S, Rodenbeck A, Guan Z et al. Sleep promoting properties of quetiapine in healthy subjects. Psychopharmacology 2004; 174(3):421-9. • DeMartinis NA, Winokur A. Effects of psychiatric medications on sleep and sleep disorders. CNS Neurol Disord Drug Targets 2007;6(1): 17-29. • Edinger JD, Bonnet MH, Bootzin RR et al. Derivation of research diagnostic criteria for insomnia: report of an American Academy of Sleep Medicine Work Group. Sleep 2004; 27(8): 1567-96. • Markowitz JS, Brown CS, Moore TR. Atypical antipsychotics. Part I: Pharmacology, pharmacokinetics, and efficacy. Ann Pharmacother 1999;33(1):73-85. • Morin AK, Jarvis CI, Lynch AM. Therapeutic options for sleep-onset and sleep-maintenance insomnia. Pharmacotherapy 2007;27(1):89-110. • Morin CM, Culbert JP, Schwartz SM. Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy. Am J Pyschiatry 1994; 151:1172-80. • National Institutes of Health. National Institutes of Health State of the Science Conference statement on Manifestations and Management of Chronic Insomnia in Adults, June 13-15, 2005. Sleep 2005; 28(9): 1049-57. • Ohayon MM, Roth T. What are the contributing factors for insomnia in the general population? J Psychosom Res 2001; 51:745-55. • Rickels K, Morris RJ, Newman H et al. Diphenhydramine in insomniac family practice patients: a double-blind study. J Clin Pharmacother 1983; 23(5-6):234-42. • Simon GE, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry 1997;154:1417-23.

  36. Questions?

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