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Major Depressive Disorder & Sex and Gender

Major Depressive Disorder & Sex and Gender

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Major Depressive Disorder & Sex and Gender

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  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 Depression, Suicide, and Gender

  11. Centers for Disease Control and Prevention, National Suicide Statistics at a Glance. Downloaded from 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

  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