Diagnosis and Management of Mood Disorders in Women in a Primary Care Setting

1. Diagnosis and Management of Mood Disorders in Women in a Primary Care Setting Katherine C. Smith, D.O. Assistant Professor

2. Goals for Today Gender differences with diagnosis and treatment of mood disorders Clinical pearls regarding the diagnosis of Mood Disorders in Women Effective screening tools in the primary care setting Treatment overview Resources

3. Psychiatry in Primary Care 54% of people with mental illness who seek treatment are exclusively seen in the �general medical sector� 25% of patients in primary care setting have a diagnosable mental illness

4. Myth Busters Men attempt suicide more often than women Antidepressants are first-line treatment for Bipolar Disorder Women are more prone to bipolar disorder than men Pregnancy is a time of emotional well-being There is a specific algorithm for the treatment of women during childbearing years 1.) Historically, pregnancy has been perceived as a time of emotional well-being- but there is limited research to support this. (was based on the low rate of psych. hospitalizations during pregnancy among women with Bipolar DO. Of course, rate increase dramatically during post-partum period) 2.) Clozapine in Category B, and Paxil is D 3._ there is no specific algorithm for the treatment of pregnant patients- depends on the severity of the disorder, and wishes of the patient, must work collaboratively with the patient, and base decision on risk factors and clinical presentation1.) Historically, pregnancy has been perceived as a time of emotional well-being- but there is limited research to support this. (was based on the low rate of psych. hospitalizations during pregnancy among women with Bipolar DO. Of course, rate increase dramatically during post-partum period) 2.) Clozapine in Category B, and Paxil is D 3._ there is no specific algorithm for the treatment of pregnant patients- depends on the severity of the disorder, and wishes of the patient, must work collaboratively with the patient, and base decision on risk factors and clinical presentation

5. Mood Disorders in Women Major Depression Dysthymia Premenstrual Dysphoric Disorder (PMDD) Bipolar Disorder type I and II

6. Depression: Prevalence and Risk Factors Depression is twice as common in women than men Hormonal factors increase vulnerability to depression Genetic contribution to depression Differences in coping strategies may lead to more severe depression in women Women are more susceptible to depressive symptoms in response to stressful life events and trauma 1.) Epidemiological studies have consistently shown: For MDD- lifetime prevalence is 21.3% for women, for men it is 12.7%; lifetime prevalence for Dysthymia is 8% women, 4.8% men- similar sex ration of 2:1; gender difference varies across the lifetime- female-male predominance beginning in early adolescence, and persisting through mid-life, then normalizing in late-adulthood. 2.) Estrogen and progesterone have been shown to affect neurotransmitter, neuroendocrine, and circadian systems implicated in mood disorders; Luteal phase of menstrual cycle- (estrogen/progesterone w/d) can be associated with dysphoric mood changes, and/or onset of worsening of MDD. PP period also common trigger for MDD/Bipolar DO. 3.) Similar heritability in men and women, no differences among relative contributions of genetic and environmental factors to depression- according to a recent study by Kendler; genetic susceptibility to PMS can account for 17% of genetic risk for lifetime MDD- Kendler 1998. 4.) Studies have shown women to have a more self-focused, ruminative style of coping in response to sadness (men in contrast use distractions strategies) Gender-specific socialization during adolescence may also contribute to the emergence of female predominance of depression. 5.)Studies have shown: Stress involving family discord, maternal depression, children, housing, reproductive problem; hx of sexual abuse more common in women than men- major risk factor; 69% abused women develop depression1.) Epidemiological studies have consistently shown: For MDD- lifetime prevalence is 21.3% for women, for men it is 12.7%; lifetime prevalence for Dysthymia is 8% women, 4.8% men- similar sex ration of 2:1; gender difference varies across the lifetime- female-male predominance beginning in early adolescence, and persisting through mid-life, then normalizing in late-adulthood. 2.) Estrogen and progesterone have been shown to affect neurotransmitter, neuroendocrine, and circadian systems implicated in mood disorders; Luteal phase of menstrual cycle- (estrogen/progesterone w/d) can be associated with dysphoric mood changes, and/or onset of worsening of MDD. PP period also common trigger for MDD/Bipolar DO. 3.) Similar heritability in men and women, no differences among relative contributions of genetic and environmental factors to depression- according to a recent study by Kendler; genetic susceptibility to PMS can account for 17% of genetic risk for lifetime MDD- Kendler 1998. 4.) Studies have shown women to have a more self-focused, ruminative style of coping in response to sadness (men in contrast use distractions strategies) Gender-specific socialization during adolescence may also contribute to the emergence of female predominance of depression. 5.)Studies have shown: Stress involving family discord, maternal depression, children, housing, reproductive problem; hx of sexual abuse more common in women than men- major risk factor; 69% abused women develop depression

7. Presentation and Course of Illness Women are more likely to present with: increased appetite and weight gain, disturbed sleep, anxiety, somatization and expressed anger. Women are three times more likely than men to attempt suicide Depressed women are more likely to have co morbid anxiety disorders, thyroid disease and pain syndromes Women have longer episodes of depression, and a chronic recurrent course Many women experience depression related to reproductive-cycle events 1.) Women have the �reverse vegetative� signs of depression (men tend to have appetite loss and weight loss)- women tend to report more depressive sx�s, no gender differences in the severity of depression. 2.) Men account for 65% of completed suicides- choose more violent means- hanging/guns; women take overdoses or drown; women are more likely than men to receive psych treatment and to have discussed their SI with care providers/families. Comorbid SA and conduct disorder increases risk for suicide 3.) Phobias, GAD, Panic DO, eating DO; also more likely to develop alcoholism once depressed; hypothyroidism, migraines (affected by menstrual cycle pregnancy, OCP), fibromyalgia, chronic fatigue, IBS, chronic pelvic pain 4.) Women more sensitive to seasonal changes: Of those who suffer from SAD: 80% are women 5.) Important to consider the influence of the menstrual cycle on course of depression: depression occurring on a regular basis during the luteal phase monthly would warrant a dx of PMDD; conversely, depression throughout the cycle, with worsening prior to menses indicate premenstrual exacerbation of depression.1.) Women have the �reverse vegetative� signs of depression (men tend to have appetite loss and weight loss)- women tend to report more depressive sx�s, no gender differences in the severity of depression. 2.) Men account for 65% of completed suicides- choose more violent means- hanging/guns; women take overdoses or drown; women are more likely than men to receive psych treatment and to have discussed their SI with care providers/families. Comorbid SA and conduct disorder increases risk for suicide 3.) Phobias, GAD, Panic DO, eating DO; also more likely to develop alcoholism once depressed; hypothyroidism, migraines (affected by menstrual cycle pregnancy, OCP), fibromyalgia, chronic fatigue, IBS, chronic pelvic pain 4.) Women more sensitive to seasonal changes: Of those who suffer from SAD: 80% are women 5.) Important to consider the influence of the menstrual cycle on course of depression: depression occurring on a regular basis during the luteal phase monthly would warrant a dx of PMDD; conversely, depression throughout the cycle, with worsening prior to menses indicate premenstrual exacerbation of depression.

8. Depression Diagnosis and Screening Within a 2 week period there is depressed mood and/or anhedonia and 5+ following: Weight changes Insomnia or hypersomnia Psychomotor agitation or retardation Fatigue Guilt Indecisiveness or decreased concentration Suicidal ideations Center for Epidemiological Studies Depression Scale Edinburgh Post Partum Depression Scale 1.) Depr. Mood and/or loss of interest/pleasure in activities; appetite changes, loss of energy, feelings of worthlessness, recurrent thoughts of death 2.) CES-D is a self-report scale which has been validated in many studies for depression- may be useful in a clinical setting for screening tool/and following depression treatment 3.) For Dysthymia- we tend to see a depressed mood for most days for atleast 2 years; lower level chronic depression- not as severe, no SI. 1.) Depr. Mood and/or loss of interest/pleasure in activities; appetite changes, loss of energy, feelings of worthlessness, recurrent thoughts of death 2.) CES-D is a self-report scale which has been validated in many studies for depression- may be useful in a clinical setting for screening tool/and following depression treatment 3.) For Dysthymia- we tend to see a depressed mood for most days for atleast 2 years; lower level chronic depression- not as severe, no SI.

9. 9-item health questionnaire derived from Primary Care Evaluation of Mental Disorders to assist general practitioners in the diagnosis and evaluation of mental disorders; developed by Columbia University in mid- 1990�s- used by many for screening� Pfizer owns the copright- available to clinicians at no cost9-item health questionnaire derived from Primary Care Evaluation of Mental Disorders to assist general practitioners in the diagnosis and evaluation of mental disorders; developed by Columbia University in mid- 1990�s- used by many for screening� Pfizer owns the copright- available to clinicians at no cost

10. Unintended Pregnancies in the U.S. 1.) Data on pregnancy intendedness was collected from the 2002 national Survey of Family Growth, and combined with birth, abortion, and population data from federal, state and governmental sources. 2.) There were 6.4 million pregnancies, but 4 million births in 2001 3.) The intended pregnancy rate declined from 56-53 per 1,000 women between 1994 and 2001. 1/20 women have an unintended pregnancy each year in the US; about half of the unintended pregnancies end in abortion each year in the US, and the other half of unintended pregnancies continued to term are associated with increased risk for: smoking, drinking, negative social health and outcomes for both baby and mother.1.) Data on pregnancy intendedness was collected from the 2002 national Survey of Family Growth, and combined with birth, abortion, and population data from federal, state and governmental sources. 2.) There were 6.4 million pregnancies, but 4 million births in 2001 3.) The intended pregnancy rate declined from 56-53 per 1,000 women between 1994 and 2001. 1/20 women have an unintended pregnancy each year in the US; about half of the unintended pregnancies end in abortion each year in the US, and the other half of unintended pregnancies continued to term are associated with increased risk for: smoking, drinking, negative social health and outcomes for both baby and mother.

11. MDD in pregnancy 10-16% of women have major depression during pregnancy Associated with problems for both mother and fetus When emerges in pregnancy, is frequently overlooked Pregnancy is neither protective, nor exacerbating for depressive disorders Under-recognized and under-treated in primary care settings Women are twice as likely as men to develop depression; rates of MDD in pregnancy approximate the rates during reproductive years 1.) Many sx�s of depression e.g.: wt gain, appetite changes, fatigue, sleep changes, loss of libido- overlap with pregnancy- diminished by clinicians. Also, patients may have medical disorders that overlap w/ depression- anemia, thyroid dysfn., gestational diabetes which make dx depression challenging. 2.); poor weight gain, tobacco, etot/drug use-mother which lead to poor obstetric outcomes; premature birth, low birth weight-fetus, newborns who are difficult to console; later in life- children of depressed mothers more prone to suicidal behavior, conduct problems, psychiatric care 3.) Depression overlooked: majority of neuroveg. signs: sleep, appetite disturbances, dec. libido, low energy- observed in pregnancy, also- certain medical disorders eg. Anemia, DM, Thyroid dysfn may resemble or be associated with depression. Clinical features which support depression: Guilt, hopelessness, anhedonia, SI.Women are twice as likely as men to develop depression; rates of MDD in pregnancy approximate the rates during reproductive years 1.) Many sx�s of depression e.g.: wt gain, appetite changes, fatigue, sleep changes, loss of libido- overlap with pregnancy- diminished by clinicians. Also, patients may have medical disorders that overlap w/ depression- anemia, thyroid dysfn., gestational diabetes which make dx depression challenging. 2.); poor weight gain, tobacco, etot/drug use-mother which lead to poor obstetric outcomes; premature birth, low birth weight-fetus, newborns who are difficult to console; later in life- children of depressed mothers more prone to suicidal behavior, conduct problems, psychiatric care 3.) Depression overlooked: majority of neuroveg. signs: sleep, appetite disturbances, dec. libido, low energy- observed in pregnancy, also- certain medical disorders eg. Anemia, DM, Thyroid dysfn may resemble or be associated with depression. Clinical features which support depression: Guilt, hopelessness, anhedonia, SI.

12. Why is this important? All women of childbearing years are potentially pregnant until proven otherwise Approximately 50% pregnancies are unplanned 10-16% women have major depression during pregnancy Risk benefit analysis ideally prior to conception, every medication change! 10-15% have MDD which approximates our normal female population, then they potentially are already on an antidepressant, like Mrs. Johnson when they become pregnant.10-15% have MDD which approximates our normal female population, then they potentially are already on an antidepressant, like Mrs. Johnson when they become pregnant.

13. Weighing the Risks and Benefits Risk of untreated mental illness Risk of relapse of psychiatric illness Effects of psychiatric illness on the fetus Teratogenicity of psychotropic medications Long term behavioral effects Incomplete reproductive safety data for medications 1.) Pharm treatment in pregnancy may be continued if the risk of mother and fetus from the disorder outweighs the teratogenic risk from the drugs. The treatment of the above disorders in women of childbearing years creates a unique dilemma for clinicians, no clinical decision is risk- free, and patients armed with the latest information may make different treatment decisions. 2.) Now we will look at the risk of exposure to the fetus: Malformations- which we will talk about- based on exposure to the fetus; Teratogen defined as: agent that interferes with organ formation, and produces organ malformation or dysfunction 2.) Neonatal Toxicity: refers to peri-natal syndromes, or spectrum of physical/behavioral symptoms observed in the neonatal period attributed to exposure at or near the time of delivery: exposure or w/d syndromes. Long-term neurobehavioral sequelae: neuronal migration and differentiation occur throughout pregnancy, CNS vulnerable to psychotropics, and toxic agents. Behavioral teratogenesis refers to potential for psychotropics to cause long-term behavioral effects 1.) Pharm treatment in pregnancy may be continued if the risk of mother and fetus from the disorder outweighs the teratogenic risk from the drugs. The treatment of the above disorders in women of childbearing years creates a unique dilemma for clinicians, no clinical decision is risk- free, and patients armed with the latest information may make different treatment decisions. 2.) Now we will look at the risk of exposure to the fetus: Malformations- which we will talk about- based on exposure to the fetus; Teratogen defined as: agent that interferes with organ formation, and produces organ malformation or dysfunction 2.) Neonatal Toxicity: refers to peri-natal syndromes, or spectrum of physical/behavioral symptoms observed in the neonatal period attributed to exposure at or near the time of delivery: exposure or w/d syndromes. Long-term neurobehavioral sequelae: neuronal migration and differentiation occur throughout pregnancy, CNS vulnerable to psychotropics, and toxic agents. Behavioral teratogenesis refers to potential for psychotropics to cause long-term behavioral effects

14. Risk of Untreated Psychiatric Illness in Pregnancy Maternal Depression may cause: Preterm birth, low birth-weight, smaller head circumference, and lower Apgar scores Contribute to poor self-care, inattention to prenatal care Women are more likely to smoke, use alcohol or illicit drugs Children of depressed mothers are more likely to have behavioral problems, delays in cognitive, motor and emotional development Risk for suicide 1.) It has been difficult to assess maternal depression on the developing fetus, new research suggests� 2.) Women frequently present with decreased appetite, less weight gain, which has been associated with negative pregnancy outcomes 3.) Depression typically associated with interpersonal difficulties, disruptions in the mother-child interactions, and attachment, may have profound impact on child development. Multiple studies have suggested behavioral problems�1.) It has been difficult to assess maternal depression on the developing fetus, new research suggests� 2.) Women frequently present with decreased appetite, less weight gain, which has been associated with negative pregnancy outcomes 3.) Depression typically associated with interpersonal difficulties, disruptions in the mother-child interactions, and attachment, may have profound impact on child development. Multiple studies have suggested behavioral problems�

15. Anxiety and Stress in Pregnancy Lead to poor outcomes Increase cortisol and adrenocorticotropic hormone levels May be associated with preeclampsia May reduce uteroplacental blood-flow Antenatal anxiety predicts postpartum anxiety and depression 1.) poor pregnancy outcomes: forceps deliveries, prolonged labor, fetal distress, preterm delivery, spontaneous abortion 2.) Increased Cortisol levels in response to stress , late in pregnancy, assoc. with lower developmental scores in infancy; Inc. Adrenocorticotropic hormone at 24 wks gestation associated with poor adaptability early in infancy; maternal anxiety in late pregnancy predicts slow mental development in 2 y/o children; animal studies show stress in pregnancy associated with neuronal death and abnormal development of fetal brain tissue. 3.) Pre-eclampsia assoc. with maternal anxiety and depression 4.) stress hormones may decrease uteroplacental blood flow 5.) Heron et al 2004: Antenatal anxiety was found to predict post-partum depression- even when controlled for depression- studied 8,323 women, concerning given that several studies have shown that maternal mood disturbances postpartum can negatively affect childhood development. 6.) Antenatal stress .depression also found to increase sleep problems, language and cognitive impairment, impulsivity, ADHD, and behavioral disturbances in children.1.) poor pregnancy outcomes: forceps deliveries, prolonged labor, fetal distress, preterm delivery, spontaneous abortion 2.) Increased Cortisol levels in response to stress , late in pregnancy, assoc. with lower developmental scores in infancy; Inc. Adrenocorticotropic hormone at 24 wks gestation associated with poor adaptability early in infancy; maternal anxiety in late pregnancy predicts slow mental development in 2 y/o children; animal studies show stress in pregnancy associated with neuronal death and abnormal development of fetal brain tissue. 3.) Pre-eclampsia assoc. with maternal anxiety and depression 4.) stress hormones may decrease uteroplacental blood flow 5.) Heron et al 2004: Antenatal anxiety was found to predict post-partum depression- even when controlled for depression- studied 8,323 women, concerning given that several studies have shown that maternal mood disturbances postpartum can negatively affect childhood development. 6.) Antenatal stress .depression also found to increase sleep problems, language and cognitive impairment, impulsivity, ADHD, and behavioral disturbances in children.

16. Depression Relapse in Pregnancy: Cohen et al. 2006: 1.) Cohen, Stowe, Burt, Hendricks, Newport, Viguera - prospective study- recruited 201 pregnant women between 1999-2003 at multiple sites; half of relapses occurred in 1st trimester, women who d/c�d their meds had a 5-fold increased risk of relapse, 68% women who discontinued their meds proximate to conception relapsed in pregnancy: (50% in 1st trimester, and 90% by the 2nd trimester); those who decreased optimal dose of antidepressant had a slightly higher risk of relapse; Pregnancy is not uniformly protective 2.) Graph: increased risk for relapse with those who INCREASED their antidepressant: was in response to more depressive sx�s, or likely a depression relapse 3.) Knowledge that � of pts who d/c meds do not relapse until 2nd trimester, may prompt decision to hold meds to avoid neonatal exposure during a critical period of organogenesis (1st 12 weeks); although in this study, there was higher risk of relapse associated with medication reintroduction 4.) Other studies support: Cohen et al. 75% of 32 euthymic women with previous depression who discontinued antidepressant before conception, relapsed; Cohen et al 2006 and Marcus et al 2005 suggest that depressive symptoms can recur in women who continue antidepressant medications during pregnancy 1.) Cohen, Stowe, Burt, Hendricks, Newport, Viguera - prospective study- recruited 201 pregnant women between 1999-2003 at multiple sites; half of relapses occurred in 1st trimester, women who d/c�d their meds had a 5-fold increased risk of relapse, 68% women who discontinued their meds proximate to conception relapsed in pregnancy: (50% in 1st trimester, and 90% by the 2nd trimester); those who decreased optimal dose of antidepressant had a slightly higher risk of relapse; Pregnancy is not uniformly protective 2.) Graph: increased risk for relapse with those who INCREASED their antidepressant: was in response to more depressive sx�s, or likely a depression relapse 3.) Knowledge that � of pts who d/c meds do not relapse until 2nd trimester, may prompt decision to hold meds to avoid neonatal exposure during a critical period of organogenesis (1st 12 weeks); although in this study, there was higher risk of relapse associated with medication reintroduction 4.) Other studies support: Cohen et al. 75% of 32 euthymic women with previous depression who discontinued antidepressant before conception, relapsed; Cohen et al 2006 and Marcus et al 2005 suggest that depressive symptoms can recur in women who continue antidepressant medications during pregnancy

17. Recommendations for Antidepressant Treatment in Pregnant Women Psychotherapy is first line for mild-moderate depression Psychotherapy + antidepressant recommended for moderate to severe depression Individualized risk-benefit analysis No hx of antidepressant treatment: SSRI antidepressant considered first-line Successful history of antidepressant treatment: data should be reviewed with mom, and considered first line 1.) Expert Guidelines composed in 2001- consisted of a panel of leading WMH experts across the country: Fluoxetine #1, Sertraline #2, followed by Tricyclics. Paxil was rated as an alternative, Luvox/Celexa later choices. 2.) If a woman plans to breast feed- and antidepressant started in 1st trimester, the same medeication be continued through delivery/during breastfeeding: Zoloft#1, Prozac /Paxil #21.) Expert Guidelines composed in 2001- consisted of a panel of leading WMH experts across the country: Fluoxetine #1, Sertraline #2, followed by Tricyclics. Paxil was rated as an alternative, Luvox/Celexa later choices. 2.) If a woman plans to breast feed- and antidepressant started in 1st trimester, the same medeication be continued through delivery/during breastfeeding: Zoloft#1, Prozac /Paxil #2

18. Recommendations continued ECT for psychotic depression Review all risks and benefits of treatment Mom�s should be monitored carefully for increased depression, mania or psychosis Dosages may need to be adjusted Goal is monotherapy and minimal effective dosage May also consider a high potency antipsychotic + antidepressant as well 1.) dosage adjustment from weight gain 2.) Risk benefit analysis should include mom, her family, her OBGYN or PCP,May also consider a high potency antipsychotic + antidepressant as well 1.) dosage adjustment from weight gain 2.) Risk benefit analysis should include mom, her family, her OBGYN or PCP,

19. PMS versus Premenstrual Dysphoric Disorder Nearly 75% women experience PMS: Bloating, weight gain, breast tenderness & swelling, aches and pains, poor concentration, sleep and appetite changes. PMDD affects 3-8% women: Irritability, tension, dysphoria, lability of mood Occurs during Luteal phase Risk factors for PMDD: genetics, normal ovarian function and serotonin Age, past or current psychiatric illness Sexual trauma Diagnosis of PMDD is obtained by 2 consecutive months of prospective daily symptom ratings 1.) pattern of behavioral, emotional, physical sx�s occur premenstrually and remit after menses- more than 100 physical and psychological sx�s associated with PMS. Mojority of women do not require medical/psych intervention. Only one of these sx�s is required for the dx of PMS!! Conservative tx�s are usually appropriate, diet, lifestyle modification, avoiding caffeine� 2.) PMDD: extremely distressing emotional/behavioral sx�s that interfere with social/occupational function, lifestyle and relationships. 3.) Etiology of PMS/PMDD largely unknown, evidence to support heritability: population based twin studies by Kendler; normal ovarian fn is the cyclical trigger for PMDD related biochemical events. Imaging studies have reported altered serotonin fn and GABAergic fn in the pathogenesis of PMDD- premenstrual irritability and dysphoria linked to the difference in sensitivity of the serotonin system in predisposed women, making them more vulnerable to hormone fluctuations. PMDD hits in the 20�s-30�s; MDD (30-70% lifetime prevalence rate) , PPD, Bipolar, Seasonal AD, previous suicide hx, anxiety disorders as well. 4.) Dx: must include 1 of the 4 core sx�s ( irritability, tension, dysphoria, mood lability) long with 5/11 total sx�s, should have a clear premenstrual onset and remit within a few days after onset of menstruation: anhedonia, dec. focus, lack of energy, sleep changes, feeling overwhelmed and other physical sx�s; 2 recognized daily recording instruments that take into consideration are: Prospective Record of Impact and Severity of Menstruation (PRISM) and COPE- handouts� 5.) Daily Record of Severity of Problems has been validated by studies, and can be useful in a clinical setting- handout given to you 1.) pattern of behavioral, emotional, physical sx�s occur premenstrually and remit after menses- more than 100 physical and psychological sx�s associated with PMS. Mojority of women do not require medical/psych intervention. Only one of these sx�s is required for the dx of PMS!! Conservative tx�s are usually appropriate, diet, lifestyle modification, avoiding caffeine� 2.) PMDD: extremely distressing emotional/behavioral sx�s that interfere with social/occupational function, lifestyle and relationships. 3.) Etiology of PMS/PMDD largely unknown, evidence to support heritability: population based twin studies by Kendler; normal ovarian fn is the cyclical trigger for PMDD related biochemical events. Imaging studies have reported altered serotonin fn and GABAergic fn in the pathogenesis of PMDD- premenstrual irritability and dysphoria linked to the difference in sensitivity of the serotonin system in predisposed women, making them more vulnerable to hormone fluctuations. PMDD hits in the 20�s-30�s; MDD (30-70% lifetime prevalence rate) , PPD, Bipolar, Seasonal AD, previous suicide hx, anxiety disorders as well. 4.) Dx: must include 1 of the 4 core sx�s ( irritability, tension, dysphoria, mood lability) long with 5/11 total sx�s, should have a clear premenstrual onset and remit within a few days after onset of menstruation: anhedonia, dec. focus, lack of energy, sleep changes, feeling overwhelmed and other physical sx�s; 2 recognized daily recording instruments that take into consideration are: Prospective Record of Impact and Severity of Menstruation (PRISM) and COPE- handouts� 5.) Daily Record of Severity of Problems has been validated by studies, and can be useful in a clinical setting- handout given to you

20. PMDD versus Premenstrual Exacerbation A recent study reported that 64% the first 1500 women enrolled in the STAR*D study retrospectively reported premenstrual exacerbation of depression When a mood or anxiety disorder is present, worsening of symptoms during luteal phase is considered premenstrual exacerbation 1.) Most PMDD sx�s are associated with mood or anxiety sx�s, PMDD should not be diagnosed when an underlying depression/anxiety disorder is present- ; the prevalence of premenstrually exacerbated axis I disorders is unknown; it is generally recommended that the primary mood/anxiety disorder should be treated first, and if premenstrual symptoms still persist, subsequent daily ratings can help identify PMDD exacerbation.1.) Most PMDD sx�s are associated with mood or anxiety sx�s, PMDD should not be diagnosed when an underlying depression/anxiety disorder is present- ; the prevalence of premenstrually exacerbated axis I disorders is unknown; it is generally recommended that the primary mood/anxiety disorder should be treated first, and if premenstrual symptoms still persist, subsequent daily ratings can help identify PMDD exacerbation.

21. Treatment of PMDD SSRI antidepressants are first-line treatment Lower doses are efficacious Continuous dosing more beneficial than intermittent luteal dosing GNRH agonists reduce physical and emotional symptoms Ethinyl Estradiol and Drospirenone is FDA approved for PMDD Ovariectomy reserved for last resort treatment Light therapy reduces depression, irritability, and physical symptoms Cognitive Behavioral Therapy and Group Therapy 1.) PMDD differs from other mood disorders in its response to treatment with antidepressants: rapid onset of response, efficacy in intermittent dosing, maximal response at low doses, and rapid recurrence of sx�s with d/c of tx. This may be due to the SSRI�s ability to enhance GABA receptor function in the brain. Consistent evidence for SSRI�s as first line tx- both emotional and physical sx�s (breast tenderness and bloating); Alprazolam and Buspirone have reduced psychological sx�s- effect is much smaller than SSRI�s. (recent metanalysis concluded cont. dosing more effective) 2.) GNRH agonists (Leuprolide, buserelin and goserelin) did reduce sx�s but not in all studies; transdermal estradiol as well as Danazol : effective in PMS 3.) (Yaz)- contains ethinyl estradiol and drospirenone (24/4) reported superiority in relieving physical/emotional sx�s; other OC- monophasic/triphasic have not been found to be effective 4.) Oophorectomy has demonstrated relief of PMS/PMDD 5.) Light therapy: 2500 lux cool-white fluorescent light for 2 hours in am/pm during symptomatic days of the luteal phase, or 10,000 lux for 30 min in the evening 1.) PMDD differs from other mood disorders in its response to treatment with antidepressants: rapid onset of response, efficacy in intermittent dosing, maximal response at low doses, and rapid recurrence of sx�s with d/c of tx. This may be due to the SSRI�s ability to enhance GABA receptor function in the brain. Consistent evidence for SSRI�s as first line tx- both emotional and physical sx�s (breast tenderness and bloating); Alprazolam and Buspirone have reduced psychological sx�s- effect is much smaller than SSRI�s. (recent metanalysis concluded cont. dosing more effective) 2.) GNRH agonists (Leuprolide, buserelin and goserelin) did reduce sx�s but not in all studies; transdermal estradiol as well as Danazol : effective in PMS 3.) (Yaz)- contains ethinyl estradiol and drospirenone (24/4) reported superiority in relieving physical/emotional sx�s; other OC- monophasic/triphasic have not been found to be effective 4.) Oophorectomy has demonstrated relief of PMS/PMDD 5.) Light therapy: 2500 lux cool-white fluorescent light for 2 hours in am/pm during symptomatic days of the luteal phase, or 10,000 lux for 30 min in the evening

22. Bipolar Disorder: Clinical Features and Course Affects 1.2% US population Bipolar type I is equal among sexes Bipolar type II is more common among women Rapid cycling, mixed mania, and more frequent episodes of depression 30-90% patients with rapid cycling bipolar disorder have hypothyroidism Mood disturbances reported with menstrual cycle 1.) later onset of Bipolar DO; Women are more prone to �mixed mania� which includes mania accompanied by syndromal depression, the depressive episodes experienced by women tend to be more lengthy and resistant to treatment and also occur in the fall and winter; Rapid cycling (mood disturbance > 4 times per year) 2.) medical disorders are also frequently comorbid with BP DO: including migraines and hypothyroidism- which can contribute to increased rapid cycling rates in women; impaired physical health as well as pain disorders; 3.) Studies showing some effects of menstrual cycle on Bipolar DO- mixed results; bottom line: women with past histories of mood disorders remain at high risk for decompensation throughout the course of their lives- during menstruation, pregnancy, postpartum and during menopause.1.) later onset of Bipolar DO; Women are more prone to �mixed mania� which includes mania accompanied by syndromal depression, the depressive episodes experienced by women tend to be more lengthy and resistant to treatment and also occur in the fall and winter; Rapid cycling (mood disturbance > 4 times per year) 2.) medical disorders are also frequently comorbid with BP DO: including migraines and hypothyroidism- which can contribute to increased rapid cycling rates in women; impaired physical health as well as pain disorders; 3.) Studies showing some effects of menstrual cycle on Bipolar DO- mixed results; bottom line: women with past histories of mood disorders remain at high risk for decompensation throughout the course of their lives- during menstruation, pregnancy, postpartum and during menopause.

23. Bipolar type I Presence of a manic episode (persistently elevated/irritable mood for at least 1 week) and 3+ symptoms persisted: **Decreased need for sleep** Inflated self-esteem Pressured speech Flight of ideas Distractibility Goal-directed activity Excessive involvement in pleasurable activities Screening: Mood Disorders Questionnaire (MDQ) 1.) Bipolar I more severe- typically will have interfered with ability to fn at work/home, require hospitalization, associated with psychotic sx�s in mania or depression; FOI (racing thoughts); pleasureable activies with consequences-spending sprees/ sexual indiscretions legal trouble� 2.) Mixed episodes may include a depressive episode and mania nearly every day during a 1 week period 3.) MDQ- can identify 7/10 people that have Bipolar DO, and screen out 9/10 that do not; useful in a primary care setting1.) Bipolar I more severe- typically will have interfered with ability to fn at work/home, require hospitalization, associated with psychotic sx�s in mania or depression; FOI (racing thoughts); pleasureable activies with consequences-spending sprees/ sexual indiscretions legal trouble� 2.) Mixed episodes may include a depressive episode and mania nearly every day during a 1 week period 3.) MDQ- can identify 7/10 people that have Bipolar DO, and screen out 9/10 that do not; useful in a primary care setting

24. Bipolar type II Presence of a Hypomanic episode (persistently elevated/irritable mood for at least 4 days) and 3+ symptoms persisted: **Decreased need for sleep** Inflated self-esteem Pressured speech Flight of ideas Distractibility Goal-directed activity Excessive involvement in pleasurable activities No psychotic symptoms!! 1.) less severe form of Bipolar DO- does not usually require hospitalization, higher functioning, easily can get by under the radar and can look like a �unipolar depression� with mood swings 2.) Again- decreased need for sleep is key- feeling rested only after a few hours1.) less severe form of Bipolar DO- does not usually require hospitalization, higher functioning, easily can get by under the radar and can look like a �unipolar depression� with mood swings 2.) Again- decreased need for sleep is key- feeling rested only after a few hours

25. General Treatment Guidelines Mixed states and rapid cycling are more common in women Antidepressants worsen: mania, hypomania, cycling, and depression First line treatment always begins with a mood stabilizer Lithium, Carbamazepine, Valproic Acid, Lamotrigine Atypical antipsychotics Once mood is stabilized, if depressive symptoms still persist, then consider augmentation with antidepressant 1.) Lithium and Lamotrigine are ideal for Bipolar Depression; Carbamazepine, Valproate better for mixed states and rapid cycling; atypical antipsychotics are alll approved for the treatment of bipolar do, acute mania and maintenance treatment- ideal for psychotic sx�s as well1.) Lithium and Lamotrigine are ideal for Bipolar Depression; Carbamazepine, Valproate better for mixed states and rapid cycling; atypical antipsychotics are alll approved for the treatment of bipolar do, acute mania and maintenance treatment- ideal for psychotic sx�s as well

26. Bipolar Disorder and Pregnancy Pregnancy seems to be �risk neutral� Relapse increases with medication discontinuation Majority of relapses in pregnancy are depressive episodes Estimates of post-partum relapse may be as high as 50% Relapse in pregnancy is a strong predictor of post-partum relapse Pregnancy is neither protective nor exacerbating for bipolar DO 1.) Few case studies/reports have shown euthymia in pregnancy; Majority studies have shown that pregnancy is a high time for relapse- especially with pharmacotherapy discontinuation- majority of relapses are depression; rates similar to relapses in women whoa re not pregnant and d/c/ their meds 2.) Impact of BPD on obstetric outcome is unknown, it can be assumed to have an adverse impact, as the majority of episodes in pregnancy are depressive. 3.) Recent survey done by Viguera and his colleagues suggested that up to 60% of patients with Bipolar DO still choose to pursue pregnancy, which underscores the importance of provideing perinatal consultation to our female patients about their risks and benefits of treatment in pregnancy- vs. risk of relapsePregnancy is neither protective nor exacerbating for bipolar DO 1.) Few case studies/reports have shown euthymia in pregnancy; Majority studies have shown that pregnancy is a high time for relapse- especially with pharmacotherapy discontinuation- majority of relapses are depression; rates similar to relapses in women whoa re not pregnant and d/c/ their meds 2.) Impact of BPD on obstetric outcome is unknown, it can be assumed to have an adverse impact, as the majority of episodes in pregnancy are depressive. 3.) Recent survey done by Viguera and his colleagues suggested that up to 60% of patients with Bipolar DO still choose to pursue pregnancy, which underscores the importance of provideing perinatal consultation to our female patients about their risks and benefits of treatment in pregnancy- vs. risk of relapse

27. Recommendations for Treatment in Pregnant Women Mild-moderate bipolar disorder: May taper or discontinue mood stabilizer prior to conception, during first trimester or throughout pregnancy Severe bipolar disorder: May continue medication throughout pregnancy Consider typical high potency antipsychotic as augmentation Psychotherapy ECT Goal is monotherapy and minimal effective dosage 1.) Mild-moderate: Especially regarding AED�s including VPA, Carbamazepine, avoid during first trimester for NTD�s, but many times women are already in their 4-5th week of pregnancy when they find out- which in the 1st 4 weeks: neural-tube development-brain and spinal cord are formed; recommended Folic Acid daily during pregnancy for prevention; VPA: 7-10% NTD, behavioral effects; Carb- Overall incidence of malformations is 5.7%, some behavioral effects; Lithium- small absolute risk of Epstein�s anomaly 1/1,000; Lamotr:- small increase in oral cleft- no inc. in malformations/ Lithium and Lamotrigine considered safer in pregnancy 2.) Severe: patients generally relapse, and have some evidence of illness even at baseline; they relapse quickly if meds are discontinued; efforts to sustain euthymia in this population are CRITICAL!, and may warrant medication continuation throughout pregnancy; Atypical antipsychotics also another choice in Bipolar DO as monotherapy, or adjunctive Tx to Lithium or Lamictal 3.) Psychotherapy is beneficial for stabilization, providing coping skills for stressors, adjustment to role as a mother, and has shown to lower the dosages of meds needed; ECT has documented safety for over 50 years- no effects on fetus 4.) Due to high risk for postpartum relapse/decompensation- if meds have been tapered/discontinued- important to monitor mom closely, and re-start meds immediately after delivery1.) Mild-moderate: Especially regarding AED�s including VPA, Carbamazepine, avoid during first trimester for NTD�s, but many times women are already in their 4-5th week of pregnancy when they find out- which in the 1st 4 weeks: neural-tube development-brain and spinal cord are formed; recommended Folic Acid daily during pregnancy for prevention; VPA: 7-10% NTD, behavioral effects; Carb- Overall incidence of malformations is 5.7%, some behavioral effects; Lithium- small absolute risk of Epstein�s anomaly 1/1,000; Lamotr:- small increase in oral cleft- no inc. in malformations/ Lithium and Lamotrigine considered safer in pregnancy 2.) Severe: patients generally relapse, and have some evidence of illness even at baseline; they relapse quickly if meds are discontinued; efforts to sustain euthymia in this population are CRITICAL!, and may warrant medication continuation throughout pregnancy; Atypical antipsychotics also another choice in Bipolar DO as monotherapy, or adjunctive Tx to Lithium or Lamictal 3.) Psychotherapy is beneficial for stabilization, providing coping skills for stressors, adjustment to role as a mother, and has shown to lower the dosages of meds needed; ECT has documented safety for over 50 years- no effects on fetus 4.) Due to high risk for postpartum relapse/decompensation- if meds have been tapered/discontinued- important to monitor mom closely, and re-start meds immediately after delivery

28. Conclusions SSRI antidepressants are first line treatment for depression and PMDD The hallmark diagnostic feature of bipolar disorder is decreased need for sleep Mood stabilizers are first line treatment for bipolar disorder All women of childbearing years are potentially pregnant until proven otherwise

29. Conclusions For women with depression who become pregnant, psychotherapy and SSRI antidepressants are considered first line treatment For women with bipolar disorder who become pregnant, psychotherapy and mood stabilizers are considered first line treatment 1.) Pre-pregnancy consultation should involve the pt, family, and other providers: PCP, OBGYN. Pt�s past psych hx, current sx�s, and attitude toward use of meds in pregnancy must be carefully assessed; most appropriate treatment algorithm depends on the SEVERITY of the illness. For milder forms, appropriate to consider d/c of meds during pregnancy, or during 1st trimester, re-introduction in 2nd trimester. Consider risk of relapse! 2.) For more severe forms of illness, reducing dosages or stopping meds in pregnancy can increase a woman�s risk for relapse significantly- as seen earlier, need to continue the medication, monitor for weight gain, metabolic syndrome. 3.) In situations which meds are indicated, attempts to select the SAFEST regimen: switch from MAOI to SSRI, or continue Cymbalta despite limited safety information. 4.) if meds were tapered prior to delivery, they should be re-started immediately after the baby is born. PP relapse can impair attachment, lead to neglect, custody loss, and infanticide. 5.) Risk benefit analysis- important to document each risk discussed with your patient, and her competence to understand the issues regarding treatment 1.) Pre-pregnancy consultation should involve the pt, family, and other providers: PCP, OBGYN. Pt�s past psych hx, current sx�s, and attitude toward use of meds in pregnancy must be carefully assessed; most appropriate treatment algorithm depends on the SEVERITY of the illness. For milder forms, appropriate to consider d/c of meds during pregnancy, or during 1st trimester, re-introduction in 2nd trimester. Consider risk of relapse! 2.) For more severe forms of illness, reducing dosages or stopping meds in pregnancy can increase a woman�s risk for relapse significantly- as seen earlier, need to continue the medication, monitor for weight gain, metabolic syndrome. 3.) In situations which meds are indicated, attempts to select the SAFEST regimen: switch from MAOI to SSRI, or continue Cymbalta despite limited safety information. 4.) if meds were tapered prior to delivery, they should be re-started immediately after the baby is born. PP relapse can impair attachment, lead to neglect, custody loss, and infanticide. 5.) Risk benefit analysis- important to document each risk discussed with your patient, and her competence to understand the issues regarding treatment

30. 1.)Weigh the risks and benefits as discussed! Work collaboratively with the patient 2.) Use the lowest effective dosage that produced euthymia, or stable anxiety/psychosis prior to pregnancy. May have to adjust dosages in pregnancy with fluid and metabolic shifts 3.) Minimize meds- especially with mood stabilizers; eg: tricyclic for depression and insomnia vs. SSRI, Trazodone and Benzo 4.) Pre-gravid trial of a medication taper- allows clinician and pt to assess clinical status prior to conception 5.) If unsure, get a consult- many website devoted to women's mental health and reproductive safety. I am also available?1.)Weigh the risks and benefits as discussed! Work collaboratively with the patient 2.) Use the lowest effective dosage that produced euthymia, or stable anxiety/psychosis prior to pregnancy. May have to adjust dosages in pregnancy with fluid and metabolic shifts 3.) Minimize meds- especially with mood stabilizers; eg: tricyclic for depression and insomnia vs. SSRI, Trazodone and Benzo 4.) Pre-gravid trial of a medication taper- allows clinician and pt to assess clinical status prior to conception 5.) If unsure, get a consult- many website devoted to women's mental health and reproductive safety. I am also available?

31. Resources Mother Risk Program www.motherisk.org Massachusetts General Women�s health www.womensmentalhealth.org United States National Library of Medicine http://toxnet.nlm.nih.gov 1.) Your source for evidence-based information about the safety or risk of drugs, chemicals, and disease during pregnancy and lactation. Dr. Koren- professor of Pediatrics, pharmacology, pharmacy and medicine University of Toronto1.) Your source for evidence-based information about the safety or risk of drugs, chemicals, and disease during pregnancy and lactation. Dr. Koren- professor of Pediatrics, pharmacology, pharmacy and medicine University of Toronto