Insomnia. Stages of sleep. Insomnia: Catching Your ZZZs

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1 Insomnia: Catching Your ZZZs Troy Payne MD, FAASM Medical Director, St. Cloud Hospital Sleep Center Diplomate of the American Academy of Psychiatry and Neurology in the Subspecialty of Sleep Medicine Insomnia Difficulty initiating sleep (initial) Difficulty maintaining sleep (maintenance) Complaint of fatigue or lack of productivity the next day Prevalence: 1/3 Americans suffer from at least intermittent insomnia More common in females More common with increasing age Stages of sleep N1: a drowsy period where sounds may still be heard but awareness is dulled; slow rolling eye movements N2: the next deeper stage where one spends most of the night; sleep spindles and K- complexes N3: deep slow wave sleep Stage R/REM: low amplitude brainwaves with only intermittent muscle movement; rapid eye movements; dreams 1

2 Causes of Transient Insomnia Environment Stress Medical illnesses Medications Caffeine Caffeine Content Coffee, brewed, 8 oz. Expresso, one shot Tea, black, brewed, 8 oz. Tea, green, brewed, 8 oz. Barq, root beer, 12 oz. Coca-Cola Classic, 12 oz. Diet Coke, 12 oz. Dr. Pepper, 12 oz. Pepsi, 12 oz. Diet Pepsi, 12 oz. Mellow Yellow, 12 oz. Mountain Dew, 12 oz. Sierra Mist, 12 oz. Sprite, 12 oz mg mg mg mg 23 mg 35 mg 46 mg 42 mg 38 mg 35 mg 53 mg 71 mg 0 mg 0 mg Caffeine Content Amp Energy, 16 oz. Full Throttle, 16 oz. Monster Energy, 16 oz. No Fear Energy, 16 oz. NOS Energy Drink, 16 oz. Red Bull, 12 oz. Rip It Energy Fuel, 8 oz. Rockstar, 16 oz. Red Bull Energy Shot, 2 oz 143 mg 144 mg 160 mg 174 mg 260 mg 120 mg 100 mg 160 mg 80 mg 2

3 Sneaky Fiorinal/Fioricet (30 mg caffeine) Excedrine (65 mg caffeine) Anacin (32 mg caffeine) Midol (60 mg) Prescription medications that can occasionally cause insomnia Alpha blockers doxazosin, prazosin, silodosin, terazosin, tamsulosin Beta blockers atenolol, carvedilol, metoprolol, propranolol, sotalol, timolol Corticosteriods prednisone, methylprednisone, triamcinolone SSRIs fluoxetine SSNRIs - venlafaxine ACE Inhibitors benazepril, captopril, enalapril, fosinopril, lisinopril, ramipril Angiotensin II receptor blockers candesartan, irbesartan, losartan Cholinesterase inhibitors donezepril, rivastigmine Second generation H1 antagonists cetirizine, loratadine, azelastine Glucosamine/Chondroitin Statins atorvastatin, lovastatin, rosuvastatin, simvastatin Methamphetamine 3

4 Perpetuating Factors Poor sleep hygiene Anxiety Napping Sleeping pills Alcohol Caffeine Nicotine Leptin Secreted by fat cells Signals the brain you are full and reduces hunger Not getting enough sleep reduces leptin making people feel more hungry than they should. People who got 4 hours of sleep/night for 6 nights had leptin levels the same as people who restricted their diet by 900 calories for three days (gave them the munchies yum!!! yum!!!) Ghrelin Secreted by the stomach Stimulates appetite and weight gain Not getting enough sleep stimulates ghrelin production (gives people the munchies yum!!! yum!!!) 4

5 Inadequate Sleep as a Risk Factor for Obesity Sample size 9588 people Data collected over 10 years People who reported an average of less than 7 hours of sleep were more likely to develop obesity People who reported sleeping more than 7 hours of sleep did not statistically gain or loose weight Gangwisch JE eta l. Inadequate sleep as a risk factor for obesity, Sleep 2005 Oct 1; 28(10): Healthy Sleep Habits The bedroom should be quiet, secure and comfortable Don t think about things in bed to much Don t watch the clock Avoid bright light, alcohol, nicotine, television, computers, naps and exercise in the late evenings Establish a relaxing routine Keep a regular bedtime and arise time Do not lay in bed awake too long (about minutes) CBT- I versus Medications Cognitive Behavioral Therapy for Insomnia is the standard of treatment given its favorable benefit:risk ratio. Meet with a sleep psychologist a few times to tune up your sleep timing, sleep habits and learn to control internal and external stimulating factors. Chronic insomniacs (at least 3 times a week for more than 3 months) should be offered CBT-I as the first primary intervention Helps avoid polypharmacy While comparable to medication in the short term, CBT-I is often superior long term We spend over $40 billion/year in the USA on sleeping pills!!! 5

6 Why use Pharmacotherapy Acute stress or short term use (job loss, divorce, etc.) Unable to access or utilize CBT-I Inadequate response to CBT-I Adjunct to CBT-I WARNING: 11% of patients reported using alcohol for insomnia Non-Prescription Agents OTC agents: sedating antihistamines Diphenhydramine Doxylamine (Unisom, Nyquil) Dietary supplements and herbal remedies Valerian Kava-Kava Chamomile Passiflora Avena sativa Diphenhydramine Well absorbed Elimination half-life of 8 hours Post-synaptic H1-receptor antagonist Postsynaptic muscarinic receptor antagonist Can decrease sleep latency, number or nocturnal awakenings, increase sleep duration and improve sleep quality * * Rickels K. J. Clinical Pharmacology 1983: 23(5-6),

7 Diphenhydramine: Side Effects Disorganized speech Altered consciousness when awake Inattention Memory Impairment Delirium Valerian Root of the Valeriana officinalis plant, a pink flowered perennial for grows wild in Europe and the Americas mg of the dried root minutes before bedtime Data on efficacy is mixed GI irritation and headache are most common side effects. Cases of hepatotoxicity. Melatonin Synthesized from the amino acid tryptophan in the pineal gland Darkness required for its secretion Melatonin regulates the suprachiasmatic nucleus (SCN: the sleep-wake clock): M1 receptor: promotes sleep M2 receptor: helps entrain the circadian clock via phase shifting effects 7

8 Melatonin Most common doses are 0.5 to 6 mg in early evening (average dose 3 mg) Unregulated and not approved by FDA Quality and purity may vary Decreases latency to sleep onset Used in some cases of sleep delayed phase syndrome and to avoid jet lag May decrease sperm count in men and fertility in women Better for circadian issues rather than insomnia Off label Medication for Insomnia Sedating antidepressants Trazodone (Desyrel) Mirtazapine (Remeron) Antipsychotics Queptiapine (Seroquel) Olanzepine (Zyprexa) Benzodiazepines (BZs) Estazolam (ProSom) Flurazepam (Dalmane) Quazepam (Doral) Temazepam (Restoril) Triazolam (Halcion) Can all be habit forming 8

9 Benzodiazepine Receptor Agonist (BzRAs) Medication Brand Sleep latency Increased sleep compared to time compared placebo to placebo Zaleplon Sonata minutes None Zolpidem Ambien minutes minutes Zolpidem ER Ambien CR minutes minutes Eszopiclone Lunesta minutes minutes Benzodiazepine Receptor Agonists (BzRAs) and Benzodiazepines (BZs) Improve sleep continuity (decrease sleep latency, increases total sleep time, decrease WASO) Sleep study changes Decreased N3 (less so with BzRAs) Reduced amplitude of slow waves Increase sleep spindles (BZs) Decreased Stage R (less so with BzRAs) Some decreased periodic leg movements BzRA and BZ Side Effects Residual daytime sleepiness Dose related anterograde amnesia Rebound insomnia upon discontinuation Other new withdrawal symptoms Respiratory suppression (worse with long acting BZs) Cognitive impairment, delirium, falls, fractures and motor vehicle accidents especially in elderly 9

10 BzRAs Warnings March 2007 FDA required all manufacturers to list complex sleep-related behaviors (walking, driving, eating, sexual behaviors) in labeling Most common with Ambien Especially in higher dose, prior history of RLS or parasomnia, history of brain injury or if concurrent use of alcohol Mortality There have been studies showing an increased mortality in patient who used medication for insomnia Unable to control for depression, anxiety and emotional factors Epidemiologic vs. controlled trials Unknown whether controls/non-controls prescribed other medications for insomnia or whether taking OTC medications or not Some thoughts on the new BzRAs Use lowest dose for the shortest time More effective on an empty stomach No recommended if advanced liver disease Caution in those with severe COPD or OSA Rapid withdrawal/reduction in dose can cause rebound insomnia and new withdrawal symptoms 10

11 Melatonin Receptor Agonist: Ramelteon (Rozerem) Most common side effects: headache, somnolence, fatigue, dizziness Contraindicated for use with fluvoxamine (Luvox) due to CYP 1A2 interaction (increases Luvox levels through the roof) No respiratory depression DEA non-scheduled Non-addictive Adverse effects: nausea, headache, fatigue Silenor Doxepin 3 or 6 mg Tricyclic antidepressant Since 2010 Non-addictive Do not prescribe to those on MAOIs or in people with untreated narrow angle glaucoma or severe urinary retention Belsomra (suvorexant) Selectively antagonizes two G-protein-coupled orexin receptors 2014 Helps with sleep initiation and maintenance Unusual or abnormal dreams Temporary weakness when falling asleep or waking up Headache Suicidal ideation Non-addictive 11

12 AASM recommendations Medication Initial in. Maintenance in. Eszopiclone helps helps Zolpidem helps helps Zaleplon helps no effect Temazepam helps helps Triazolam helps no effect Ramelteon helps no effect Doxepin no effect helps Suvorexant no effect helps 93.. AASM does NOT recommend for Insomnia Diphenhydramine Melatonin L-tryptophan Valerian Tiagabine Trazodone Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. J Clin Sleep Med Feb 15;13(2): St. Cloud Hospital Sleep Center and CentraCare Sleep Medicine Clinic 1586 County Road 134 St. Cloud, MN

Insomnia: Updates in Medical Management. Michael Newnam M.D.

Insomnia: Updates in Medical Management Michael Newnam M.D. Sleep Neurobiology Delicate balance of excitatory and inhibitory neurotransmitters that control the switch between wakefulness and sleep Circadian