SOUND ASLEEP: MEDICATIONS AND BEHAVIORAL STRATEGIES FOR OLDER ADULTS

SOUND ASLEEP: MEDICATIONS AND BEHAVIORAL STRATEGIES FOR OLDER ADULTS Jeannie Kim Lee, PharmD, BCPS, CGP, FASHP Colleges of Pharmacy and Medicine The University of Arizona Learning Objectives: Describe the role and risk versus benefit of sleep medications in older adults. Discuss effective behavioral strategies for sleep in older adults. Identify safe medications to use for sleep in older adults. DISCLOSURE OF COMMERCIAL SUPPORT Jeannie Kim Lee, PharmD, BCPS, CGP, FASHP does not have a significant financial interest or other relationship with manufacturer(s) of commercial product(s) and /or provider(s) of commercial services discussed in this presentation. 1

Sound Asleep: Medications & Behavioral Strategies for Sleep in Older Adults Jeannie K Lee, PharmD, BCPS, CGP, FASHP University of Arizona College of Pharmacy Arizona Center on Aging 2 Objectives 1. Describe the role and risk versus benefit of sleep medications in older adults 2. Discuss effective behavioral strategies for sleep in older adults 3. List safe medications to use for sleep in older adults Sleep Disorders in Older Adults 3 Chronic insomnia = unsatisfactory sleep on 3 nights/week x 3 months Prevalence of insomnia increases with age 57% of older adults complain of insomnia Late-life insomnia often prompts selfmedication with OTC sleep aids or alcohol 2

60 50 40 30 20 10 0 4 Prevalence (%) of Chronic Sleep Complaints Among Older Adults 22 15 31 27 Trouble falling Awakes during asleep night 21 22 16 8 Awakes frequently Naps during day 12 13 Awakes not rested 57 57 Any chronic sleep disorder Men Women Source: Foley, Monjan, Brown et al. SLEEP. 18:425-32, 1995. 5 Sleep Stages and Aging http://www.healthcentral.com/common/images/8/8692_6443_5.jpg 6 Objectives 1. Describe the role and risk versus benefit of sleep medications in older adults 3

7 Medicalization of sleeplessness Data from National Ambulatory Medical Care Survey Diagnosis of insomnia increase >7-fold Rx for benzodiazepine increased ~30-fold A public health concern Year 1993-1994 2007 Office visits for 2.7 million 5.7 million sleeplessness Insomnia diagnosis 840,000 6.1 million Office visits for 2.5 million 3.7 million benzodiazepine Rx Rx for benzodiazepines 540,000 16.2 million Moloney ME, Konrad TR, Zimmer CR. Am J Public Health. 2011;101:1429-1433. 8 Insomnia epidemic Rise in # of older adults Sleep architecture change Comorbid conditions and medications Nonbiological issues in younger adults Stress Multiple social roles Increased technology use Targeted marketing of sleep medications Moloney ME, Konrad TR, Zimmer CR. Am J Public Health. 2011;101:1429-1433. 9 Insomnia epidemic 4

10 Solutions for sleepless America Annual sleep screening Satisfaction with sleep Daytime fatigue interfering with activities Snoring, breathing problems Excessive movements in bed 11 Sleep Assessment Tools Sleep questionnaires EPWORTH Sleepiness Scale Sleep Evaluation by AASM Home sleep logs Symptom checklists Bed partner interviews Psychological screening tests Sleep studies for obstructive sleep apnea AASM American Academy of Sleep Medicine 12 Annual sleep screening Complete medical history Psychosocial problems Cardiovascular problems Respiratory problems Nocturia, restless leg syndrome, cramps Pain Obesity Medications Rx and OTC Alcohol use Smoking 5

13 Differential diagnosis Central sleep apnea (primary or drug/substance induced) Cheyne-Stokes breathing pattern (associated with heart failure) High-altitude periodic breathing Jet-lag disorder Medication-related insomnia Depression Obstructive Sleep Apnea-Hypopnea Syndrome Periodic Limb Movement Disorder Restless Legs Syndrome Sleeplessness and Circadian Rhythm Disorder http://emedicine.medscape.com/article/1187829-differential 14 Medications/substances that cause or aggravate sleep disorder in older adults Class examples α-blockers β-blockers Calcium channel blockers Diuretics Decongestants Respiratory Hormones Antiepileptic Stimulants Substances Medication examples clonidine atenolol felodipine, nisoldipine furosemide phenylephrine, pseudoephedrine altuterol, theophylline corticosteroids, thyroid hormones lamotrigine, phenytoin dextroamphetamine, methylphenidate caffeine, alcohol, nicotine 15 Treatment of Insomnia 1. Treat the underlying cause 2. Non-pharmacological therapy Try a couple of them Try a combination of them 3. Pharmacological therapy 6

16 Role of drug therapy When non-pharmacological therapies fail When benefits outweigh risks Short-term use Need to continuously evaluate 17 Pharmacological Therapy Sedative-hypnotics Benzodiazepines Non-benzodiazepines Antidepressants Antipsychotics Anticonvulsants Melatonin agonists OTCs: Antihistamines, Melatonin, Valerian 18 Risk versus benefit 2005 meta-analysis of short-term treatment of sedative hypnotics in older people Compared potential benefits (subjective reports) to risks (adverse events and morning-after impairment) RCT of any sleep medications taken at least 5 nights 60 years and older with insomnia without other psychiatric diagnosis 24 studies included (2417 participants) Glass J, Lanctot KL, Herrmann N, et al. BMJ, doi:10.1136/bmj.38623.768588.47 (published 11 November 2005) 7

Sleep quality 19 20 Cognitive adverse effects Glass J, Lanctot KL, Herrmann N, et al. BMJ, doi:10.1136/bmj.38623.768588.47 (published 11 November 2005) 21 Sedative versus placebo Benefit Sleep quality improved with effect size 0.14 (small effect size = 0.2) Total sleep time increased by mean 25 minutes # of nighttime awakenings decreased by 0.63 All significant improvements but small Number needed to treat = 13 Risk Adverse cognitive events 5 times higher Adverse psychomotor events (dizziness, loss of balance) 2.61 times higher Daytime fatigue 4 times higher No difference between benzo and non-benzo Number need to harm = 6 Glass J, Lanctot KL, Herrmann N, et al. BMJ, doi:10.1136/bmj.38623.768588.47 (published 11 November 2005) 8

Memory Health FDA Adverse Event Reporting System Top 10 prescription drugs linked to memory side effects (2004-2011) 1. Zolpidem ER (Ambien CR) 2. Zolpidem (Ambien) 3. Gabapentin (Neurontin) 4. Sodium Oxybate (Xyrem) 5. Natalizumab (Tysabri) 6. Interferon Alfa-2b (PEG-Intron) 7. Topiramate (Topamax) 8. Atorvastatin (Lipitor) 9. Paroxetine (Paxil) 10. Clonazepam (Klonapin) Health, Medical, and Science Updates 2012 23 2014 CDC Report Emergency Department (ED) visits due to psychiatric medication 2011 US Data 90,000 ED visits/year due to adverse events 32% of older adults hospitalized #1 culprit = zolpidem (ambien ) 1/5 ED visits in older adults Hampton LM, Daubresse M, Chang HY, et al. JAMA Psychiatry. Doi:10.1001/jamapsychiatry.2014.436 ED visits in adults Top 10 psychiatric drugs causing adverse events 1. Zolpidem (Ambien) 2. Quetiapien (Seroquel) 3. Alprazolem (Xanax) 4. Lorazepam (Ativan) 5. Haloperidol (Haldol) 6. Clonazepam (Klonopin) 7. Trazodone (Oleptro) 8. Citalopram (Celexa) 9. Lithium salts 10. Risperidone (Risperdal) Hampton LM, Daubresse M, Chang HY, et al. JAMA Psychiatry doi:10.1001/jamapsychiatry.2014.436 9

25 Why zolpidem? What about Benzos? Medicare Part D (2003) Did not cover benzodiazepines Covered zolpidem until 2013 State Medicaid on benzodiazepines 41 states with complete coverage (AZ) Use remained stable 6 states with partial supplemental coverage Use remained stable 1 state with no coverage Tennessee Immediate and significant reduction Hampton LM, Daubresse M, Chang HY, et al. JAMA Psychiatry doi:10.1001/jamapsychiatry.2014.436 26 27 AGS Choosing Wisely campaign #4 Don t use benzodiazepines or other sedative-hypnotics in older adults as first choice for insomnia, agitation or delirium. Falls and fracture risk Automobile accidents Leading to morbidity and mortality American Geriatric Society Five Things Physicians and Patients Should Question: www.choosingwisely.org 10

28 AVOID Benzodiazepine hypnotics Beers Criteria: avoid any type for insomnia Long-acting: active metabolite accumulates in older adults Diazepam (Valium) Insomnia + Anxiety: short-term therapy Short-acting: for sleep latency only Alprazolam (Xanax), Triazolam (Halcion) Intermediate-acting: for sleep latency & nighttime awakening Temazepam (Restoril), Estazolam (Prosom), Lorazepam (Ativan) American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2012;60:616-631 29 Benzodiazepine Hypnotics Adverse events Central Nervous System (CNS) depression/motor coordination Drowsiness, dizziness, and lightheadedness Falls, fractures, and motor vehicle accidents Cognitive impairment, delirium Anticholinergic side effects Physical and psychological dependence Addiction/drug seeking Withdrawal symptoms American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2012;60:616-631 30 EMPOWER Trial Eliminating Medications through Patient Ownership of End Results To reduce benzodiazepine use among older adults using direct patient education 303 long-term benzodiazepine users aged 65-95 years from 30 community pharmacies 15 pharmacies randomized to educational intervention; 15 pharmacies randomized to control Participants, physicians, pharmacists, evaluators blinded Tannenbaum C, Martin P, Tamblyn R, et al. JAMA Intern Med. 2014;174(6):890-898. 11

31 EMPOWER Intervention Eliminating Medications through Patient Ownership of End Results Tannenbaum C, Martin P, Tamblyn R, et al. JAMA Intern Med. 2014;174(6):890-898. 32 EMPOWER Intervention Eliminating Medications through Patient Ownership of End Results Tannenbaum C, Martin P, Tamblyn R, et al. JAMA Intern Med. 2014;174(6):890-898. 33 EMPOWER Intervention Eliminating Medications through Patient Ownership of End Results Tannenbaum C, Martin P, Tamblyn R, et al. JAMA Intern Med. 2014;174(6):890-898. 12

34 EMPOWER Trial Eliminating Medications through Patient Ownership of End Results Did you know? Ask yourself Side effects As you age Alternatives Lifestyle changes Stress and anxiety management Patient testimonial Step-by-step tapering-off program Under doctor or pharmacist Tannenbaum C, Martin P, Tamblyn R, et al. JAMA Intern Med. 2014;174(6):890-898. 35 EMPOWER Intervention Eliminating Medications through Patient Ownership of End Results Tannenbaum C, Martin P, Tamblyn R, et al. JAMA Intern Med. 2014;174(6):890-898. 36 EMPOWER Trial Eliminating Medications through Patient Ownership of End Results Discontinuation of benzodiazepine at 6 months 27% in intervention group Dose reduction in additional 11% 5% in control group Number needed to treat = 4 Multivariate sub-analyses Age >80, sex, duration of use, indication, dose, previous attempt to taper, polypharmacy (10 or more) did not have significant interaction Tannenbaum C, Martin P, Tamblyn R, et al. JAMA Intern Med. 2014;174(6):890-898. 13

37 AVOID Non-benzodiazepine Hypnotics Beers Criteria: avoid >90days Increase sleep time by <12 mins Delirium, falls, fractures, sleep driving, sleep eating, sleep walking, short-term amnesia True insomnia with no other option Short-acting: for sleep latency Zaleplon (Sonata), Zolpidem (Ambien) Long-acting: for sleep latency & nighttime awakening Zolpidem ER (Ambien CR), Eszopiclone (Lunesta) American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2012;60:616-631 38 AVOID Antipsychotics Beers Criteria: increase stroke & mortality in dementia patients (black box warning) Dizziness, hypertension, metabolic syndrome (weight gain, increased blood sugar, increased cholesterol) Not recommended without psychiatric problems Examples: Olanzapine (Zyprexa), Risperidone (Risperdal), Quetiapine (Seroquel) American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2012;60:616-631 39 AVOID Tricyclic Antidepressants Beers Criteria: highly anticholinergic, sedating, cause orthostatic hypotension Dizziness, anxiety, confusion, delusions, disorientation, hallucinations, nightmares Unlabeled use for insomnia Examples: Amitriptyline (Elavil), Imipramine (Tofranil), Clomipramine (Anafranil) American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2012;60:616-631 14

40 AVOID Sedating SSRI Unlabeled use for insomnia Anticholinergic side effects Hyponatremia prevalent in older adults Prolonged QT, GI and sexual side effects Examples: Paroxetine (Paxil) insomnia up to 24% Citalopram (Celexa) insomnia up to 15% 41 AVOID Barbituates Beers Criteria: High rate of physical dependence Tolerance to sleep benefits Risk of overdose at low doses Hypotension, syncope, dizziness, agitation, anxiety, confusion, hallucinations, nightmares, hangover effect Limited evidence for efficacy Examples: Phenobarbital, Secobarbital (Seconal), butabarbital (Butisol) American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2012;60:616-631 42 AVOID Chloral Hydrate Miscellanious hypnotic Beers Criteria: Tolerance occurs within 10 days Risk of overdose at low doses 3 times recommended dose Arrhythmia, hypotension, torsades de pointes, delirium, dizziness, dependence, hallucinations, handover effect, nightmares, vertigo American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2012;60:616-631 15

43 AVOID 1 st -Generation Antihistamines Beers criteria: Highly anticholinergic Reduced clearance Tolerance when used as hypnotic Confusion, drug mouth, constipation, blurred vision, urinary retention Examples: Hydroxyzine (Vistaril), American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2012;60:616-631 44 AVOID OTC Sleep Aids (1 st -Gen antihistamines) Diphenhydramine & Doxylamine Beers criteria: highly anticholinergic Increased half-life up to 14hrs Diphenhydramine Doxylamine Nytol Sominex Unisom SleepTabs Tylenol PM Excedrin PM Equaline Sleep Aid Advil PM Unisom SleepGels Good Sense Sleep Aid Zzzquil American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2012;60:616-631; Gerontological Society of America. Sleep Helath and the Appropriate Use of OTC Sleep Aids in Older Adults, White Paper. November 2013 45 AVOID Alcohol May induce sleep onset but fragments sleep in 2 nd part of night Increase daytime sleepiness and promote sleep disturbance Valerian root May slightly decrease sleep latency but lacks evidence May be hepatotoxic Gerontological Society of America. Sleep Helath and the Appropriate Use of OTC Sleep Aids in Older Adults, White Paper. November 2013 16

46 Objectives 1. Describe the role of drug therapy for sleep in older adults 2. Discuss effective behavioral strategies for sleep in older adults 47 Non-pharmacologic Therapy Behavioral therapy Sleep hygiene Cognitive therapy Cognitive-behavioral therapy Relaxation technique Sleep restriction/compression Exercise Tai Chi Acupuncture 48 Behavioral Strategies A review of 48 clinical trials Almost 80% benefited from behavioral therapies for at least 6 months after completion with no side effects Counteract sleep deterrents Sleep hygiene (diet, exercise, substance use) Environmental modifications (light, temperature, noise) Self-Help CBT-I older adults with chronic conditions Sleep hygiene and behavioral strategies Significant improvements in sleep quality & efficiency Morin CM. Principles and practices of sleep medicine. 4 th ed. Philadelphia, PA: Elsevier/Saunders; 2005:726-737; Stepanski EJ, Wyatt JKSleep Med Rev. 2003;7(3):215-225; Morgan K, et al. J Am Geriatr Soc 2012;60:1803-1810. 17

Sleep Hygiene 49 Sleep as long as necessary to feel rested and do not stay in bed longer Regular sleep schedule and bedtime routine Avoid caffeinated beverages after noon Avoid alcohol and smoking within 2 hours of bedtime Exercise regularly at least 4-5 hours before bedtime Create a comfortable sleeping environment Avoid daytime naps 50 Cognitive Therapy To educate patients on: Misunderstandings regarding sleep Identify false beliefs about sleep Normal changes in sleep with aging Abnormal/pathological changes in sleep 51 Tai Chi Originally developed for self defense Movement and balance Improvements in subjects 65-92 years Sleep latency Sleep quality Sleep duration J Am Geriat Soc. 2004 Jun; 52(6): 892-900 18

52 Acupuncture A possible option for patients to explore Historically conflicting results on efficacy of auricular acupuncture in improving insomnia in older adults Most recent findings showed positive effects Int J Clin Pract. 2008 Nov;62(11):1744-52. J Gerontol Nurs. 2007 Aug;33(8):23-8; quiz 30-1. 53 Objectives 1. Describe the role of drug therapy for sleep in older adults 2. Identify risk versus benefit of sleep medications 3. List safe medications to use for sleep in older adults 54 Sedative Antidepressants Trazodone (Oleptro) Unlabeled use Dose <150mg qhs Improves sleep latency and duration Efficacy may be short-lived Mirtazapine (Remeron) Unlabeled use Used for insomnia + depression + weight loss 19

55 Sedative Antidepressant and Anticonvulsant Doxepin (Silenor) - TCA Beers Criteria: Limit dose to <6mg/day highly anticholinergic at higher dose Increases sleep duration and decreases nighttime awakenings Gabapentin (Neurontin) Usually for neuropathic pain or restless leg syndrome sedating side effect Renal dosing required 56 Remelteon Melatonin receptor agonist Modest efficacy Improves sleep latency Increases sleep time Improves circadian sleep cycle Not habit forming No hangover sedation or rebound insomnia Adverse effects: Dizziness, myalgia, headache 57 OTC Melatonin Decreases sleep latency Improves quality of sleep and morning alertness Improves circadian sleep cycle No evidence of rebound insomnia or withdrawal effects No difference in nighttime awakenings or total sleep time 20

58 Summa Health Project Retrospective chart review Risk of delirium: Initial nursing assessment and Six-Item Screener (SIS) score Development of delirium: Nursing Delirium Screening Scale (NuDESC) Shumate LA, Fosnight SM, Dinuoscio D, Wilford R. The Effects of Melatonin and Trazodone on Delirium in Hospitalized Patients. Summa Akron City Hospital, Akron, OH 59 Shumate LA, Fosnight SM, Dinuoscio D, Wilford R. The Effects of Melatonin and Trazodone on Delirium in Hospitalized Patients. Summa Akron City Hospital, Akron, OH 60 NNT = 7 * Shumate LA, Fosnight SM, Dinuoscio D, Wilford R. The Effects of Melatonin and Trazodone on Delirium in Hospitalized Patients. Summa Akron City Hospital, Akron, OH 21

61 CAM meta-analysis Randomized controlled trials (n=12) Tai-chi (n=3) Acupuncture (n=4) OTC melatonin (n=5) Outcome measures Pittsburg Sleep Quality (PSQI) scores Index of Severity of Insomnia (ISI) Self-report (total sleep time, sleep latency) Polysomnography or actigraphy Song HW, Slack M, Lee JK. meta-analysis of alternative and complementary medicine for the treatment of insomnia Forest Plot of Three CAM Interventions in Treating Insomnia 62 Alternative Treatment for Insomnia in Older Adults Group by Study name Total N Statistics for each study Std diff in means and 95% CI Intervention Std diff Lower Upper in means limit limit p-value -1.26-2.18-0.34 0.01 Acupuncture de Silva, 2005 22 Acupuncture Huang, 2006 29-0.47-1.42 0.49 0.34 Acupuncture Yeung, 2009 60-0.66-1.18-0.14 0.01 Acupuncture Yeung, 2011 52-0.51-1.06 0.04 0.07 Acupuncture -0.66-0.99-0.33 0.00 Melatonin -0.41-0.98 0.16 0.16 Braam, 2009 49 Melatonin Kayumov, 2001 22-0.38-0.91 0.15 0.16 Melatonin Kumar, 2007 40-0.23-0.85 0.39 0.47 Melatonin Montes, 2002 10-0.26-1.03 0.51 0.51 Melatonin Zhdabova, 2001 30-0.10-0.54 0.34 0.64 Melatonin -0.26-0.51-0.01 0.04 Tai Chi -0.36-0.91 0.20 0.21 Irwin, 2008 52 Tai Chi Li, 2004 118-0.58-0.95-0.21 0.00 Tai Chi Wang, 2010 29-0.30-1.04 0.44 0.42 Tai Chi -0.48-0.76-0.20 0.00 Overall -0.43-0.59-0.27 0.00-1.00-0.50 0.00 0.50 1.00 Favors Treatment Favors Control Meta Analysis Song HW, Slack M, Lee JK. meta-analysis of alternative and complementary medicine for the treatment of insomnia 63 Considerations for treatment Symptom pattern Treatment goals Past treatment responses Patient preference and cost Try non-pharmacological approach first! If using medication therapy Comorbid conditions Concurrent medications drug interactions Adverse effects Dependence Alcohol consumption Beers Criteria 22

64 Yes, older people are different 65-year-old cyclist 75-year-old golfer 85-year-old with poor vision and osteoporosis 95-year-old nursing home resident Yet, extended sedative use is not justified for any of them! Sound Asleep: Medications & Behavioral Strategies for Sleep in Older Adults Jeannie K Lee, PharmD, BCPS, CGP, FASHP University of Arizona College of Pharmacy Arizona Center on Aging jlee@pharmacy.arizona.edu 23