Z.DOLEV PSYCHIATRIST WOMEN MENTAL HEALTH

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1 Z.DOLEV PSYCHIATRIST WOMEN MENTAL HEALTH

2 Gender-Specific Differences in Psychiatry Major Depression Bipolar disorder Anxiety disorders Borderline P.D Eating disorders Insomnia PTSD Suicidal behavior Women vs. Men More common Less frequent Suicide attempted More frequent 1,2 Suicide completed Less frequent alcoholism/substance abuse Less frequent 1. Kornstein SG, et al. Psychopharmacol Bull. 2002(suppl 3);36: Kessler RC, et al. Arch Gen Psychiatry. 1999;56:

3 Anxiety Disorders are More Prevalent in Women Men Any Anxiety Disorder Specific phobia Social anxiety disorder (SAD) Agoraphobia with panic Generalized anxiety disorder (GAD) Panic disorder Kessler RC, et al. Arch Gen Psychiatry2006 ;51:8-19..

4 Gender & Mood Disorders Unipolar Depression Female to male ratio = 2 : 1 Bipolar Disorder Bipolar 1: women = men, Bipolar II: women > men American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington DC, American Psychiatric Association, 2000

5 Depression: Gender-Differences

7 Symptoms of Depression in Men vs Women (JAMA Psychiatry. Published online August 28, 2013) Study shows men just as likely to be depressed as women

9 Women take more psychotropic medications than Men. About 2/3 of antidepressants and tranquilizers dispensed in the United States are prescribed to women. Haack S Pharmacogenomics 2009

11 Antidepressant pharmacokinetics: Gender -Differences

12 women have a % higher risk of developing side-effects than men

13 Antidepressants side effects: Gender-Differences

14 SSRI/SNRI in women receiving Tamoxifen

16 REPRODUCTIVE PSYCHIATRY

17 Reproductive Psychiatry The 5 Ps Puberty Postpartum Perimenopause Pregnancy Premenstrual

18 Mood and Female Reproductive Cycle Childbearing years menses Pregnancy Menopause Premenstrual disorders (pms,pmdd) Mood and pregnancy Postpartum mental disorders Mood and perimenopausal period

19 There are subgroups of women who are vulnerable to mood disorders in Premenstrual Pregnancy Postpartum Perimenopause Burt and Stein, Chapter: Treatment of Women, In American Psychiatric Press Textbook of Psychiatry, expected date of publication, May 2008

21 Normal Sleep for Healthy Adults Average total nocturnal sleep time is 6-8 hours Sleep latency minutes Sleep stages: NREM(STAGE 1,2,3,4,) REM Sleep cycle: min Ohayon MM, Carskadon MA, Guilleminault C, Vitiello MV. Sleep. 2004;27:

22 Average Hours of Sleep Vary with Age Iglowstein I, Jenni OG, Molinari L, Largo RH. Pediatrics. 2003;111:

10-30 30-40 40-50 Children 8-12 40-60 20-30 20-30

23 Changes of sleep with age Sleep Time (h) Stages 1-2 (%) Stages (%) REM (%) Infants Children Adults Elderly

24 Insomnia is Highly Prevalent Chronic insomnia is estimated to affect 10% of the population. 30% to 50% of the general population are estimated to have insomnia of any duration or severity. 1. Agency for Healthcare Research and Quality. Manifestations and Management of Chronic Insomnia in Adults. Accessed February 11, Ohayon MM. Sleep Med Rev. 2002;6:

Risk Factors for Insomnia Female Elderly

Parkinson s disease Heart disease Respiratory

restless leg syndrome Depression Anxiety

hypomania Stress Worry- Conditioning Marital

Unemploymen t Poor working conditions Lower

drinks containing caffeine in the afternoon

26 Risk Factors for Insomnia Female Elderly Primary sleep disorder Obesity Pain Arthritis Parkinson s disease Heart disease Respiratory disease Gastrointestinal disease Sleep apnea, restless leg syndrome Depression Anxiety Tension Substance or alcohol abuse Mania or hypomania Stress Worry- Conditioning Marital separation Divorce Death of spouse Unemploymen t Poor working conditions Lower social status Smoking Drinking alcohol or drinks containing caffeine in the afternoon or evening Exercising close to bedtime Irregular schedule Night-shift work Temperature Lighting Noise Interruptions Partner s sleep habits Thyroid disorder Menopause

27 Insomnia and Psychiatric disorders

29 FDA: Cut Ambien Dosage for Women The manufacturers of Ambien CR, must lower their recommended doses for women (and other sleeping medications that contain the active ingredient zolpidem) Jan. 10, 2013

30 medications that contain zolpidem STILNOX AMBIEN ZODORM

31 the recommended dose of Stilnox for women from 10 mg to 5mg and from 12.5 mg to 6.25 mg for extended release products Ambien CR

32 The decision was driven by a series of clinical trials studies, which showed that zolpidem levels in women may be high enough to impair alertness in tasks after waking up, including driving.

33 The risk is especially high in women, according to the FDA

34 This is not just about Ambien that s just the tip of the iceberg, said Dr. J Clayton, director for the Office of Research on Women s Health at the NIH. There are a lot of sex differences for a lot of drugs.

35 Do doctors treat men and women too equally? The FDA s decision on Ambien renews push for gender-based medicine January 15, 2013 Jonnelle Marte

36 ARE THERE GENDER DIFFERENCES IN SLEEP?

37 MEN AND WOMEN SLEEP DIFFERENTLY

38 Ulrich Voderholzer, M.D., Feige, Ph.D., Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Germany

39 Sleep complaints are twice as prevalent in women, yet 75% of sleep research is performed on men. Ulrich Voderholzer, M.D., Feige, Ph.D., Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Germany

40 In this respect insomnia resembles other psychiatric disorders that occur more frequently in women such as anxiety and depressive disorders.

41 Since insomnia is frequently a symptom of anxiety and depression, It remains an open question whether the comorbidity with psychiatric disorders fully explains the gender differences

42 or whether gender influences sleep independently from psychiatric conditions

43 GENDER DIFFERENCES IN SLEEP BECOME APPARENT AFTER THE ONSET OF PUBERTY.

45 WHILE HEALTHY WOMEN APPEAR TO OBJECTIVELY HAVE BETTER QUALITY SLEEP THEN MEN, WOMEN OF ALL AGE GROUPS REPORT MORE SLEEP PROBLEMS.

46 Women are more likely then men to present to their physician their complaints related to sleep. As a result women are more likely to be prescribed hypnotics. Men would use alcohol more commonly than women to self-treat insomnia.

47 Why insomnia Is more prevalent In Women?

48 psychiatric morbidity(mood and anxiety disorders) Psychosocial factors(being separated,single or widowed) sex steroids (Hormonal changes across the reproductive cycle) 1. Ohayon MM. Sleep Med Rev. 2002;6: Soares CN, Murray BJ. Psychiatr Clin North Am. 2006;29:

49 WHAT ABOUT SEX STEROIDES AND SLEEP?

50 WOMEN S LIFE STAGES ARE MARKED BY PHYSIOLOGIC CHANGES WHICH IMPACT THE RISK FOR INSOMNIA.

51 Sleep and Reproductive- Hormones Insomnia is common in Childbearing years Menstrual period Pregnancypostpartum Menopause

52 Hormonal Effects Estrogen REM sleep cycles 1 Number of spontaneous arousals 1 Progesterone Sedating 2 Increases NREM 2 1. Manber R, Kuo TF, Cataldo N, Colrain IM. Sleep. 2003;26: Eichling PS, Sahni J. J Clin Sleep Med. 2005;1:

53 Sleep and the Menstrual Cycle In late luteal phase (PMS/PMDD) subjective sleep complaints

54 Sleep and Pregnancy insomnia is common: Abdominal mass, fetal movements, bladder distention Restless leg syndrome (third trimester) OSA (obstructive sleep apnea)

55 Postpartum Sleep 30% new mothers report disturbed sleep First-time mother's sleep is most disturbed Wolfson AR, Lee KA. Pregnancy And The postpartum period: sleep during postpartum recovery. In: Kryger MH, Roth T, Dement W. Principles and Practice of Sleep Medicine. 4th ed. Philadelphia, PA: Saunders; 2005:

MENOPAUSE AND INSOMNIA 40% of early perimenopausal women report sleep difficulties 2 ; many are at higher risk of developing depressive symptoms 1.

56 MENOPAUSE AND INSOMNIA 40% of early perimenopausal women report sleep difficulties 2 ; many are at higher risk of developing depressive symptoms 1. Young T, Rabago D, Zgierska A, Austin D, Laurel F. Sleep. 2003;26: Gold EB, Sternfeld B, Kelsey JL, et al. Am J Epidemiol. 2000;152:

57 Menopause transition Estradiol FSH LH Inhibin Progesterone Testosterone Perimenopause Years Post menopause

58 Co-occurrence of core menopause brain symptoms Hot flashes Sleep Depression

59 Sleep quality is worse in peri- and postmenopausal women % p< Pre Early peri Late peri Post (no HT) Adapted from Kravitz HM, et al. Menopause 2003 Ohayon MM. Arch Int Med 2006; Young T, et al. Sleep 2003; Hollander LE, et al. OBGYN 2001; Owens JF, Matthews KA. Maturitas 1998; Shaver J, et al. Sleep 1988

60 Sources of sleep disturbance in women during menopause transition 1. Hot flashes 2. Anxiety 3. Depression 4. Chronic pain 5. Poor health 6. Sleep apnea 7. Periodic limb movement syndrome Freedman RR, Roehrs TA, Menopause 2007; Young T et al, Am J Resp Crit Care Med 2003

61 Severity of HOT FLASHES associated with INSOMNIA % with insomnia p< None Mild Moderate Severe Ohayon MM. Arch Int Med 2006

62 Treatment of insomnia during the menopause Insomnia+ hot flushes Insomnia+ depression insomnia HRT CIRCADIN SSRI/SNRI

63 WHAT ABOUT MELATONIN AND GENDER?

65 Melatonin secretion decreases as a person ages 300 Median nocturnal serum melatonin concentrations (pg/ml) Age Waldhauser et al. 1988;

66 Interactions between Estrogens, Serotonin and Norepinephrine.

67 Estrogen and Neurotransmitter Systems Serotonergic System Estrogen Catecholaminergic System 1 Sherwin BB, Suranyi-Cadotte BE. Biol Psychiatry. 1990;28: Aylward M. IRCS J Int Res Commun Med Sci. 1973;1: Mize AL, et al. Neuroendocrinology. 2001;73: van Amelsvoort TAMJ, et al. Psychoneuroendocrinology. 2001;26:

68 Estrogen and Melatonin melatonin Serotonin? Estrogen

69 The effects of estrogen on pineal function varies. Consequently no consensus has been reached concerning, the effect of estrogen on melatonin secretion

70 The decline in the nocturnal serum melatonin concentration that occurs from 17 to 45 years of age, and, postmenopause may be related to pineal aging.

71 It is not known whether the transient increase in nocturnal melatonin secretion that occurs during peirmenopause is a physiologic consequence of changes in the gonadal pineal feedback system

72 Results of a 6-year longitudinal study on a human population which was equally divided between men and women subjects revealed a sexspecific decline in melatonin secretion in women but not in men S.R. Pandi-Perumal a, N. Zisapel b, V.(2006) Srinivasan c, D.P. Cardinali

73 The prevalence of insomnia in older females is higher as in twice as males. it is possible that a decrease in the circulating levels of melatonin in aged menopausal women be one of the important factors., S.R. Pandi-Perumal a, N. Zisapel b, V. Srinivasan c, D.P. Cardinali

75 Sleep and sleep disturbances: biological basis and clinical implications N. Zisapel In patients with insomnia aged 55 years and older the mean melatonin production at night is about two-thirds of that in aged matched individuals without insomnia, and about one third of that in healthy adults aged years. Cell. Mol. Life Sci. DOI /s Birkhuser Verlag, Basel, 2007

76 Sex-related differences in sleep have also been noted patterns in older aged women: longer REM latencies and increased REM sleep periods as compared to age-matched elderly men. S.R. Pandi-Perumal a, N. Zisapel b, V. Srinivasan c, D.P. Cardinali

77 Review Melatonin and sleep in aging population S.R. Pandi-Perumal a, N. Zisapel b, V. Srinivasan c, D.P. Cardinali The mechanism by which melatonin levels decline with aging has not been fully explained.

Healthy Sleep Tips Along the Way!

Healthy Sleep Tips Along the Way! Women and Sleep What You Will Learn The Benefits and Importance of Sleep States and Stages of the Sleep Cycle Unique Physiology of Women s Sleep Common Disorders in Women that Affect Sleep Women s Role