Major Depressive Disorder & Sex and Gender

1. Major Depressive Disorder & Sex andGender

2. At the end of the lecture, you will be able to: • Describe the features of Major Depressive Disorder (MDD) • Discuss the prevalence of MDD in the community • Define sex differences in MDD • Screen for MDD using validated screening tools • Describe effective treatments for MDD Objectives

3. Defining MDD

4. DSM-5 Defined Depressive Disorders:1 • Major Depressive Disorder (MDD) • Disruptive Mood Dysregulation Disorder • Persistent Depressive Disorder (Dysthymia) • Premenstrual Dysphoric Disorder • Substance/Medication-Induced Depressive Disorder • Depressive Disorder Due to Another Medical Condition • Other Specified Depressive Disorder • Unspecified Depressive Disorder What is Depression?

5. Major Depressive Disorder (MDD) is defined as the presence of five or more of the following symptoms occurring for at least 2-weeks. At least one of these symptoms must include either Depressed Mood or Anhedonia:1 • Depressed mood • Anhedonia (diminished pleasure in activities) • Significant weight loss/gain • Insomnia • Psychomotor agitation • Fatigue • Feelings of worthlessness/guilt • Trouble concentrating • Recurrent thoughts of death, suicidal ideation, or suicide planning or attempts What is MDD?

6. In addition, symptoms must:1 • Cause clinically significant distress or difficulty with everyday functioning • Not be solely attributable to the effects of a substance • Not be solely attributable to another medical condition or to another mental disorder • Not include a history of mania/hypomania What is MDD?

7. Epidemiology of MDD

8. Groups at highest risk for MDD:1,2 • 18-24 and 45-64 years of age • Up to a 3:1 Female to Male ratio • African American, Hispanic, or multiple races • Less than a high school education • Divorced/Previously married • Unable to work or unemployed • Without health insurance Point Prevalence DSM-IV-TR Criteria as assessed with the PHQ-8 Other Depression: Minor Depression, Depression NOS, Dysthymia (CDC, 2010) Epidemiology

9. Pre-pubertal children • Affected by MDD at equal rates3 • Women • Average onset of first major depressive episode- 24.3 years old4 • Longer depressive episodes4 • Greater overall severity of symptoms reported5 • Commonly present with comorbidities including anxiety disorders and Bulimia nervosa4 • Men • Average onset of first major depressive episode- 26.5 years old4 • Report fewer symptoms than women6 Disease Course

10. The possibility of suicidal behavior exists at all times during MDD episodes.1 • About 11.26 of every 100,000 people die by suicide every year. NIMH Suicide Factsheet. Downloaded from www.nimh.gov/health/statistices/suicide Depression, Suicide, and Gender

11. Centers for Disease Control and Prevention, National Suicide Statistics at a Glance. Downloaded from http://www.cdc.gov/violenceprevention/suicide/statistics/mechanism02.html on 11/20/2014 Suicide by Age, Sex, and Mechanism (2005-2009)

12. Biological Considerations

13. Women • Worsening of symptoms of MDD several days before Menses.3 • Women entering menopause early are nearly twice as likely to develop depressive symptoms.7 • Women who entered menopausal transition and concurrently initiated hormonal therapies displayed a decreased risk of developing severe depressive symptoms compared to those who did not.7 Hormones Menstrual Cycle Science Art. (2009). Menstrual Cycle [Digital Image]. Retrieved from http://vesuvias.wordpress.com/2009/01/04/menstrual-cycle/

14. Men • Low levels of Testosterone associated with depressive symptoms in older men.8 • Testosterone therapy has been shown to improve mood and depressive symptoms in men with low Testosterone.8 Hormones

15. Research suggests a strong role for genetics in MDD: • 15% risk of MDD in first degree relatives compared to 5.4% in the general population.9 • Several genes tied to MDD: • DISC1- Critical to neuronal migration to the hippocampus.9 • TSNAX- Associated with DISC1.9 • DAOA- Influences NMDA excitatory transmission.9 Genetics

16. Genes involved in Estrogen metabolism have been tied to increased depression symptoms in premenopausal women: • 1. CYP1A1 rs2606345 CC genotype: • Caucasian women have 2.5-fold higher odds of reporting depressive symptoms.10 • African American women have 10-fold higher odds of reporting depressive symptoms.10 • 2. CYP19 rs936306 TT genotype: • Japanese women show 5-fold higher odds of reporting depressed symptoms.10 • 3. 17HSD rs615942 TT genotype: • Chinese women reported higher levels of depressive symptoms.10 Genetics

17. Physical and Sexual Abuse • Victims of physical abuse more prevalent in men.11 • Victims of sexual abuse more prevalent in women.11 • Abuse has been linked to increased risk of developing depression, PTSD, substance abuse, personality disorders, suicidal behavior, and aggression in adulthood.11 • Substance Abuse • Men are more likely to suffer from alcohol abuse disorders than women.2 • Substance abuse can predispose individuals to mental illness, including depression.2 Other Considerations

18. Marriage • Never-married, divorced or separated, and widowed individuals report higher levels of depression than continually married individuals.12 • A satisfying marriage offers similar benefits to men and women.12 • Exiting or living in a strained marriage confers similar costs for men and women, posing increased risks for mental illness, including MDD.12 • Remarriage is often more advantageous to men’s well-being than women’s.12 Other Considerations

19. Screening for MDD

20. US Preventive Services Task Force Recommendations:13 • Screen when staff-assisted depression care supports are in place to assure accurate diagnosis, effective treatment, and follow-up. (Grade B) • Do not routinely screen when staff-assisted depression care supports are not in place. (Grade C) Screening

21. Most direct screening tool… YOU! • Over the past 2 weeks, have you felt down, depressed, or hopeless? • Over the past 2 weeks, have you felt little interest or pleasure in doing things? Another screening tool • Patient Health Questionnaire (PHQ2 and PHQ9).14 *A positive screen should trigger an evaluation using the DSM-5 criteria for MDD. Screening

22. Treatment for MDD

23. Overall, women are more likely to to acknowledge and seek help for mental illness than men.15 • Use of medical services for MDD, ranked by frequency:15 • Women with physical illness • Women without physical illness • Men with physical illness • Men without physical illness Treatment for MDD

24. Selective Serotonin Reuptake Inhibitors (SSRIs) • Most commonly prescribed. • Side effects- G.I. dysfunction, agitation, anxiety, suicidal thoughts/behaviors.16 • Ex: Citalopram, Escitalopram, Fluoxetine, Paroxetine, Sertraline • Atypical Antidepressants • Side effects- G.I. dysfunction, insomnia, low blood pressure, blurred vision.17 • Ex: Bupropion, Mirtazapine, Nefazodone, Trazodone, Venlafaxine • Tricyclic Antidepressants (TCAs) • Broad mechanism of action, therefore more side effects than other classes- G.I. dysfunction, dry mouth, confusion, sexual dysfunction.18 • Ex: Amitriptyline, Amoxapine, Doxepin, Nortriptyline Medication for MDD

25. Monoamine Oxidase Inhibitors (MAOIs) • Oldest class of antidepressants. • Dangerous interaction with any food/drink containing Tyramine, Side effects- G.I. dysfunction, dizziness, insomnia, headaches, sexual dysfunction.19 • Ex: Isocarboxazid, Phenelzine, Selegiline, Tranylcypromine • Atypical Antipsychotics • Side effects- G.I. dysfunction, increased risk of C.V. disease, sexual dysfunction.20 • Ex: Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone, Ziprasidone Medication for MDD

26. Womenare more likely to take medication for treatment of MDD.21 • SSRImedications function best in the presence of estrogen.22 • Sertraline andFluoxetine (SSRI) shown to work especially well for women.22,23 • Womenhave a better response to MAOIs than men.22 • TCA medications work better in men. • Men show better overall response to Imipramine (TCA).22 • Women metabolize Clomipramine (TCA) slower than men.22 Medication- Gender Considerations

27. SSRIsare often offered as first line medications for MDD.24 • SSRIsassociated with several side effects in newborns:24 • Persistent newborn pulmonary hypertension with maternal use after 20 weeks of gestation • Premature birth • Lower birth weight • Neonatal withdrawal or adaptation syndrome • Of particular concern, Paroxetine has been associated with first-trimester cardiovascular malformations and is typically avoided during the first trimester Medication- Pregnancy

28. Effective psychological treatments:25 • Cognitive and Behavioral Therapies • Interpersonal Therapy • Problem-Solving Therapy • Self-Management Therapy In general, Antidepressant Medication and Psychotherapy are equally effective.26 Antidepressant Medication PLUS Psychotherapy is even more effective.26, 27 Psychological Treatment for MDD

29. MDD is a common mental health disorder. • While MDD in men and women presents similarly, there are important differences with regard to age of onset, severity, and treatment. • More research is needed to further our understanding of MDD as it relates to sex and gender. Conclusions