SLEEP DISORDER IN THE ELDERLY EFFECT OF MELATONIN

SLEEP DISORDER IN THE ELDERLY EFFECT OF MELATONIN THERAPY DORON GARFINKEL, M. D. HEAD, GERIATRIC PALIATIVE DEPARTMENT SHOHAM GERIATRIC MEDICAL CENTER PARDES – HANA, ISRAEL

Normal Sleep & Normal Aging: Our Internal Biological Clock v The biological clock resides in the brain v It helps regulate when we feel sleepy and when we are alert v It works in tandem with light and dark, and our body temperature and hormones

MELATONIN N ACETYL -5 - METHOXYTRYPTAMINE AN INDOLE-AMINE SECRETED IN RESPONSE TO DARKNESS FROM THE PINEAL GLAND ITS SYNTHESIS & EXCRETION ARE REGULATED BY AN ENDOGENOUS CLOCK LOCATED IN THE HYPOTHALAMUS THAT IS ENTRAINED TO THE EXTERNAL LIGHT - DARK CYCLE

MELATONIN N ACETYL -5 - METHOXYTRYPTAMINE THE HORMONE INDUCES SLEEP THROUGH ITS SYNCHRONIZING EFFECT ON THE INTERNAL BIOLOGICAL CLOCK EASILY CROSSES THE BLOOD BRAIN BARRIER (B. B. B. ) IS RAPIDLY METABOLIZED IN THE LIVER AND OVER 85% ELIMINATED IN THE URINE AS 6 SULPHATOXY - MELATONIN (6 - S - MT)

EFFECT OF AGE ON MELATONIN Z THERE IS AN AGE-RELATED CHANGE IN THE DAILY RHYTHM OF MELATONIN Z SERUM MELATONIN CONCENTRATIONS DECREASE IN OLD AGE Z IN HEALTHY ELDERLY INSOMNIACS, 6 -S MT IS SIGNIFICANTLY LOWER AND ITS ONSET AND PEAK TIME ARE DELAYED IN COMPARISON TO AGE MATCHED CONTROLS WITH NO SLEEP DISTURBANCES

URINARY 6 - SULPHATOXY MELATONIN (6 - S- MT) EXCRETION NORMAL ELDERS / PATIENTS

EXOGENOUS MELATONIN Therapeutic Effects EXERTS SYNCHRONIZING EFFECTS ON CIRCADIAN RHYTHMS - IT PHASE ADVANCES SLEEP OF PATIENTS SUFFERING FROM DELAYED SLEEP- PHASE SYNDROME CAN FACILITATE THE POST - FLIGHT ADAPTATION OF JET - LAG RESYNCHRONIZES THE SLEEP - WAKE CYCLE OF BLIND PEOPLE

EXOGENOUS MELATONIN Characteristics IS NOT ASSOCIATED WITH SERIOUS SIDE EFFECTS IS SHORT LIVED IN HUMANS SERUM HALF LIFE IS ONLY 40 -50 MINUTES

CONTROLLED - RELEASE MELATONIN J ENABLES RESTORATION OF NORMAL SERUM MELATONIN CONCENTRATIONS BY CONTROLLED DOSAGE AND TIMING J ACHIEVES A PHARMACOKINETIC PROFILE SIMILAR TO THAT OF ENDOGENOUS MELATONIN SECRETED BY THE PINEAL GLAND J THE QUALITY OF SLEEP IS MUCH BETTER THAN THAT ACHIEVED BY REGULAR , SHORT ACTING MELATONIN J COMPLIANCE IS IMPROVED ESPECIALLY IN THE ELDERLY

RESEARCH PROJECTS STUDY DESIGN RANDOMIZED, PLACEBO CONTROLLED DOUBLE - BLIND SUBJECTS GIVEN ± CROSSOVER DESIGN EITHER 2 mg OF CONTROLLED - RELEASE MELATONIN (CIRCADINTM, NEURIM PHARMACEUTICALS , ISRAEL) OR A PLACEBO, TWO HOURS BEFORE DESIRED BEDTIME , FOR THREE WEEKS - SEVERAL MONTHS

SUBJECTS E E E ADULTS AND ELDERLY PEOPLE LIVING IN THE COMMUNITY WHO SUFFERED FROM SLEEP DISTURBANCES INITIALLY, PEOPLE LIVING IN MEDITERRANEAN TOWERS, A RESIDENTIAL CENTER FOR SENIOR CITIZENS IN ISRAEL THEN, PATIENTS SUFFERING FROM DIABETES MELLITUS, HEART DISEASE, HYPERTENTION etc ± SLEEPING PILLS. . .

RESEARCH PROJECTS TOOLS A SLEEP QUESTIONNAIRE Ø ASSESSMENT OF SLEEP QUALITY FOR THREE CONSECUTIVE NIGHTS, BY WRIST ACTIGRAPHY WHILE SUBJECTS WERE SLEEPING AT HOME Ø MOTION RECORDING ANALYSED USING AN AUTOMATIC SCORING ALGORHYTHM Ø URINE COLLECTED AT 3 HOUR INTERVALS OVERNIGHT, URINARY 6 -S MT ASSAYED BY R. I. A. OR ELISA Ø

STUDY PROTOCOL URINE COLLECTION ACTIGRAPH (3 NIGHTS) RUN IN PLACEBO 1 WEEK CR MELATONIN OR PLACEBO 3 WEEKS WASH OUT PLACEBO PLACEB OR CR MELATONIN 1 WEEK 3 WEEKS

EFFECTS OF CR MELATONIN ON SLEEP PARAMETERS IN ELDERLY PATIENTS

EFFECTS OF CR MELATONIN ON SLEEP PARAMETERS IN ELDERLY PATIENTS

EFFECTS OF CR MELATONIN ON SLEEP PARAMETERS IN ELDERLY PATIENTS

IMPROVEMENT OF SLEEP QUALITY IN ELDERLY PEOPLE BY CONTROLLED- RELEASE MELATONIN D. GARFINKEL, M. LAUDON, D. NOF, N. ZISAPEL LANCET 1995; 346: 541 - 44

CONCLUSIONS J CONTROLLED - RELEASE MELATONIN SIGNIFICANTLY IMPROVES SLEEP QUALITY IN ELDERLY INSOMNIACS IN WHOM MELATONIN OUTPUT WAS IMPAIRED J MELATONIN REPLACEMENT THERAPY SHORTENS SLEEP LATENCY, IMPROVES SLEEP EFFICIENCY AND DECREASES W. A. S. O.

IMPROVEMENT OF SLEEP QUALITY IN DIABETIC PATIENTS BY CONTROLLED RELEASE MELATONIN

Impaired nocturnal melatonin secretion in Non-dipper hypertensive patients Jonas M, Garfinkel D, Zisapel N, Laudon M, Grossman E BLOOD PRESS 12 (1); 19 -24, 2003.

BENZODIAZEPINES BENZODIAZEPINS ARE WIDELY USED IN THE ELDERLY POPULATION FOR THE INITIATION OF SLEEP VERY FREQUENTLY, COMPLAINTS ABOUT POOR SLEEP MAINTENANCE PERSIST DESPITE BENZODIAZEPIN TREATMENT

BENZODIAZEPINES WE REPORTED A DECREASED MELATONIN OUTPUT IN ELDERLY PEOPLE SUFFERING FROM INSOMNIA (Compared to Controls) MELATONIN CAN IMPROVE SLEEP QUALITY IN MELATONIN - DEFICIENT ELDERLY PEOPLE MELATONIN PRODUCTION CAN BE INHIBITED BY BENZODIAZEPINS !!!

FACILITATION OF BENZODIAZEPINE DISCONTINUATION BY CONTROLLED-RELEASE MELATONIN DOSE REDUCTION - Period I % PLACEBO GOAL 1 P < 0. 05 2 3 4 MELATONIN 5 6 WEEKS

FACILITATION OF BENZODIAZEPINE DISCONTINUATION BY C. R. MELATONIN BENZODIAZEPINE DISCONTINUATION PLACEBO MELATONIN % 5 6 week

FACILITATION OF BENZODIAZEPINE DISCONTINUATION BY C. R. MELATONIN BZD. DOSE REDUCTION VS SLEEP QUALITY 7. 56. 55. 5 - % ~11% 0 1 2 3 4 <<< MELATONIN 5 <<<< 6 WEEKS

FACILITATION OF BENZODIAZEPINE DISCONTINUATION BY C. R. MELATONIN TWO YEARS AFTER TERMINATION OF THE STUDY BENZODIAZEPINE DOSE REDUCTION STOPPED TAKING BZD 0 N C. R. MELATONIN WITHOUT C. R. MELATONIN 78% 60% 52% 8% REDUCED BZD DOSAGE (Average 30% of Initial BZD Dose) 18% STILL ON BENZIDIAZEPINES & STOPPED C. R. MELATONIN FAILURE 22%

CONCLUSIONS CONTROLLED - RELEASE MELATONIN CAN FACILITATE BENZODIAZEPINE DISCONTINUATION OR ENABLES A SIGNIFICANT DOSE REDUCTION OF BENZODIAZEPINES, WHILE MAINTAINING THE SAME OR BETTER SLEEP QUALITY

FACILITATION OF BENZODIAZEPINE DISCONTINUATION BY MELATONIN : A NEW CLINICAL APPROACH D. GARFINKEL, N. ZISAPEL, J. WAINSTEIN, M. LAUDON, Arch Int Med 159: 2456 -60, 1999

הכנס הראשון לרפואה בגיל השלישי 82 באפריל 3002 הפרעות שינה בקשישים בבתי אבות ובמחלקות ד"ר דורון גרפינקל סיעודיות מחלקה גריאטרית פליאטיבית שהם -המרכז המשולב לרפואת הגיל השלישי פרדס חנה

APPROACH TO SLEEP DISORDERS IN THE NURSING HOME SETTING SLEEP DISORDERS AND SLEEP FRAGMENTATION ARE VERY COMMON IN NURSING HOME RESIDENTS … UNFORTUNATELY, THERE IS LITTLE DATA ON THE EFFECTIVENESS OF SLEEPING MEDICATIONS AND THE SPECIFIC MANAGEMENT OF SLEEP DISORDERS IN THIS SETTING. Allesi CA & Schnelle JF. Sleep Med Rev 2000; 4(1): 45 - 56 (Review Article)

SLEEP DISTURBANCES AMONG NURSING HOME RESIDENTS SLEEP DISTURBANCES WERE COMMON AMONG THE RESIDENTS ACTIGRAPHY OF DEMENTED LONG TERM PATIENTS SHOWED SLEEP EFFICIENCY OF 75%, A MEAN SLEEP ONSET LATENCY OF ONE HOUR, A MEAN W. A. S. O. OF MORE THAN TWO HOURS, MORE THAN 13 HOURS WERE SPENT IN BED Fetveit A, Bjorvatn B. Int J Geriatr Psychiatry 2002; 17: 604 - 9

THE SLEEP OF OLDER PEOPLE IN HOSPITAL AND NURSING HOMES THE MAIN CAUSES OF SLEEP DISTURBANCES IN BOTH SETTINGS WERE: NEEDING TO GO TO THE TOILET, NOISE PAIN AND DISCOMFORT Ersser & al. J Clin Nurs 1999; 8(4): 360 - 8

APPROACH TO SLEEP DISORDERS IN THE NURSING HOME SETTING A VARIETY OF FACTORS CONTRIBUTE TO THESE SLEEPING DIFFICULTIES L AGE RELATED CHANGES IN SLEEP L THE HIGH PREVALENCE OF DEMENTIA, DEPRESSION, MEDICAL ILLNESS AND MEDICATIONS THAT AFFECT SLEEP N RESPIRATORY DISTURBANCES OF SLEEP L LIFESTYLE CHARACTERISTICS SUCH AS: INACTIVITY, LARGE AMOUNTS OF TIME SPENT IN BED, LACK OF BRIGHT LIGHT EXPOSURE AND POOR SLEEP HYGIENE AND THE DISRUPTIVE NIGHT-TIME NURSING HOME ENVIRONMENT Allesi CA & Schnelle JF. Sleep Med Rev 2000; 4(1): 45 - 56 (Review Article)

THE IMPACT OF SEDATIVE-HYPNOTIC USE ON SLEEP SYMPTOM IN ELDERLY NURSING HOME RESIDENTSS 145 institutionalized elderly subjects, mean age 83. 0 (range 65 - 105 years) in 12 nursing homes At baseline: One or more sleep related complaints were present in 65% of the residents. No relationship was found between use of sedative - hypnotic agent and the presence or absence of sleep complaints. AFTER 6 MONTHS OF FOLLOW UP: Improvement in functional status was significantly associated with improved sleep (p< 0. 005). Monane M, Glynn RJ, Avorn J. Clin Pharmacol Ther 1996; 59(1): 83

THE IMPACT OF SEDATIVE-HYPNOTIC USE ON SLEEP SYMPTOM IN ELDERLY NURSING HOME RESIDENTSS CONCLUSIONS: THERE WAS NO RELATIONSHIP BETWEEN DECREASED USE OF SEDATIVE - HYPNOTIC AGENTS AND WORSENED SLEEP, OR BETWEEN THEIR INCREASED USE AND IMPROVED SLEEP REPORTS Monane M, Glynn RJ, Avorn J. Clin Pharmacol Ther 1996; 59(1): 83

THE SLEEP OF OLDER PEOPLE IN HOSPITAL AND NURSING HOMES NO DISCERNIBLE DIFFERENCE WAS FOUND IN QUALITY OF SLEEP AND WHETHER PATIENTS FELT RESTED OR NOT, BETWEEN THOSE PATIENTS ON HYPNOTIC MEDICATION AND THOSE WHO WERE NOT Ersser & al. J Clin Nurs 1999; 8(4): 360 - 8

THE NURSING HOME AT NIGHT: EFFECT OF AN INTERVENTION ON NOISE, LIGHT AND SLEEP CONCLUSIONS: The significant reduction in noise and light events … did not lead to significant improvement in the day sleep and most night sleep measures AN INTERVENTION THAT COMBINES BOTH BEHAVIORAL AND ENVIRONMENTAL STRATEGIES AND THAT ADDRESSES DAYTIME BEHAVIORAL FACTORS ASSOCIATED WITH POOR SLEEP (eg. Excessive time in bed) WOULD POTENTIALLY BE MORE EFFECTIVE IN IMPROVING THE NIGHT SLEEP & THE QUALITY OF LIFE OF NURSING HOME RESIDENTS

SLEEP PATTERNS AND MORTALITY AMONG ELDERLY PATIENTS IN A GERIATRIC HOSPITAL Sleep disturbances were studied as a mortality risk in 272 institutionalized elderly patients Mortality after two years was significantly higher in the nighttime insomnia, daytime sleepiness and sleep onset delay groups. Sleep disturbances may be one of the symptoms indicating poor health or functional deficits, and be an independent risk factor for survival. Manabe K & al. Gerontology 2000; 46(6): 318 - 22

Nocturnal Respiratory Disturbances INTRODUCTION : Chronic hypoxia due to alveolar hypoventilation and/or disturbance in ventilation/perfusion ratio, are usually the result of a variety of cardiopulmonary & neurological maladies whose prevalence is increasing with age.

Nocturnal Respiratory Disturbances INTRODUCTION : Breathing problems in general & sleep apnea in particular, are both increasing with age and represent the main causes for clinically significant, chronic night hypoxia Sleep disturbances may aggravate hypoxia and lead to increased mortality and morbidity

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution RESULTS:

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution CONCLUSIONS: IN SPITE OF NORMAL OR ONLY MILDLY IMPAIRED RESULTS OF BOTH THE SUBJECTIVE SLEEP REPORTS AND ARTERIAL BLOOD GASES & SPIROMETRY A SIGNIFICANT NIGHT HYPOXIA ACCOMPANIED WITH MANY PERIODS OF RESPIRATORY DISTURBANCES (APNEA / HYPOPNEA) WERE FOUND IN MOST OF THE SAME SUBJECTS Seleznev I, & al. Unpublished Data

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution CONCLUSIONS: ALL SUBJECTS WITH SIGNIFICANT NOCTURNAL RESPIRATORY DISTUEBANCES WERE OFFERED THERAPY (CPAP). . … HOWEVER. . . ONLY 3 ELDERS AGREED TO TRY THIS NON INVASIVE TREATMENT ! Seleznev I, & al. Unpublished Data

MELATONIN FOR TREATMMENT OF SUNDOWNING IN ELDERLY PERSONS WITH DEMENTIA COHEN - MANSFIELD J, GARFINKEL D, LIPSON S. Arch Gerontol & Geriatr 31: 65 -76, 2000

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution OBJECTIVES: Z. Determine the prevalence of hypoxia in elderly people living in a nursing home Z. Find out whether this hypoxia was influenced by the circadian rhythm Z. Look for correlations between apparent maladies or clinical manifestations and relevant laboratory respiratory findings. Seleznev I, & al. Unpublished Data

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution Patients : Elderly volunteers living in a nursing home at the Shoham Geriatric Center Pardes-Hana, Israel Exclusion criteria : * Significant disability defined as Karnofski Performance Index < 50 * Significant cognitive impairment MMSE score<18 * Unstable medical conditions Seleznev I, & al. Unpublished Data

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution Methods : k Subjective assessment of the quality of sleep (a questionnaire) k Objective assessment of sleep quality was performed in all subjects in their own bed by 8 channel polysomnography 4. 4 Pulmonary function assessments were performed using bedside Spirometry in the evening before polysomnography 4 Arterial blood gases were determined in the morning following polysomnography. These measurements were used to calculate several parameters, enabling a quantitative comprehensive evaluation of sleep and breathing patterns

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution RESULTS: 87% of the subjects had Pa. O 2 above 70 mm. Hg, 9% had values of 55 - 70 mm. Hg, only 4% had a Pa. O 2 below 55 mm. Hg. The severity of dyspnea (according to the NYHA Functional Classification) had a significant positive correlation with Pa. CO 2 (p=0. 034, R=0. 306) and negative correlation with Pa. O 2 (p=0. 015, R=0. 348). Seleznev I, & al. Unpublished Data

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution RESULTS: 99 patients met our criteria but only 51 volunteered to participate (14 men, 37 women) average 82. 1± 6. 89 (range 70 to 95). 36 patients had hypertension, 20 suffered from ischemic heart disease (7 also had CHF), 11 had COPD; Depression was diagnosed in 7, diabetes mellitus in 6, previous CVA in 5 hypothyroidism in one. Seleznev I, & al. Unpublished Data

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution RESULTS: The subjective assessment of sleep quality according to the sleep questionnaire: 57% complained of severe sleep disorders 27% had mildly-moderately disturbed sleep 16% reported a good night sleep No correlation was found between subjective sleep quality and nocturnal oxygen saturation, Pa. O 2 and Pa. CO 2. Seleznev I, & al. Unpublished Data

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution RESULTS: Seleznev I, & al. Unpublished Data

Nocturnal Respiratory Disturbances in a Prolonged Care Geriatric Institution RESULTS:

APPROACH TO SLEEP DISORDERS (IN THE NURSING HOME SETTING) SLEEP DISORDERS SHOULD BE HANDLED BY THE PHYSICIAN IN THE SAME CLINICAL APPROACH AS THAT USED FOR OTHER SYMPTOMS OR SIGNS: FIRST OF ALL, DEFINE THE UNDERLYING CAUSE & MAKE THE CORRECT DIAGNOSIS

Evaluating Causes of Insomnia ä Situational factors that are major stressors such as a life trauma or an upcoming important event ä Environmental factors such as too much noise, temperature that are too hot or too cold, or working a night shift ä Factors related to medications, both prescription and nonprescription (i. e. CNS stimulants/ activating antidepressants) ä Medical problems such as pain, endocrine, menopause, BPH, incontinence, CHF, PUD/GERD, COPD, allergic rhinitis, seizure d/o

APPROACH TO SLEEP DISORDERS (IN THE NURSING HOME SETTING) 1. RULE OUT AND TREAT SITUATIONS LEADING TO SECONDARY SLEEP DISORDERS PARTICULARY SLEEP APNEA (PATIENT’S STORY, ANXIETY, DEPRESSION, PHYSICAL, IMAGING & LAB FINDINGS). 2. NO APPARENT UNDERLYING CAUSE FOR SLEEP DISORDER and ADVANCED AGE CONSIDER A PRIMARY MELATONIN DISORDER . A. PROVE IT: CHECK OVERNIGHT URINE FOR 6 -STM B. CONSIDER A THERAPEUTIC TRIAL WITH 2 mg OF CONTROLLED - RELEASE MELATONIN. . . OR 4. TRY A SLEEPING PILL… PREFERABLY NOT A BENZODIAZEPINE AS THE FIRST CHOISE