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Psychiatric Disorders Associated with Female Reproductive Function

I. Mood and anxiety disorders are more common in women

Peak incidence of psychiatric illness during the childbearing years

II. Premenstrual Dysphoric Disorder (PMDD)

A. DSM-IV classification as Depressive Disorder, Not Otherwise Specified

B. Research criteria defined in DSM-IV

1. At least five symptoms emerging during the luteal phase and remitting with onset of menses

Depressed mood 

Decreased interest

Anxiety or tension 

Impaired concentration

Affective lability 

Lethargy or fatigue

Anger or irritability 

Change in appetite

Feeling overwhelmed 

Sleep disturbance

Physical symptoms: Breast tenderness, bloating, weight gain, joint/muscle pain

2. Marked interference with work, school, or social activities

3. Not merely an exacerbation of another disorder (e.g., MDD, panic disorder)

4. Confirmed by prospective daily ratings during two consecutive cycles

D. Diagnosis

• In less than 5% of woman

• Distinguish from premenstrual syndrome (PMS): physical complaints and minor mood changes which occurs in 30 to 40% of women

• Onset during teens or early 20s

• Symptoms may vary from cycle to cycle

• History of mood disorder is frequent

• Rule out exacerbation of axis I disorder (MDD, bipolar disorder)

E. Treatment

• Aerobic exercise

• Avoidance of alcohol, caffeine

• Oral contraceptives (monophasic preparation)

• Alprazolam (Xanax)

• Antidepressants SSRIs: sertraline, fluoxetine Non-serotonergic agents may be less effective Continuous vs. intermittent (late luteal) dosing

• Gonadotropin-releasing hormone agonists (Lupron) Induction of menopause --> osteoporosis, cardiovascular disease Estrogen add-back

• Surgical oophorectomy- irreversible

IV. Psychiatric Illness During Pregnancy

• Pregnancy does not appear to be protective or to reduce risk

• High rates of relapse associated with medication discontinuation

V. Psychotropic Medications During Pregnancy

A. Risks associated with fetal exposure

• Congenital malformation (3-4% with no known exposure)

• Neonatal toxicity or withdrawal

• Neurobehavioral sequelae- very little information

B. FDA Use-In-Pregnancy Pregnancy Categories

• A: Controlled studies show no risk No psychotropic agents

• B: No evidence of risk in humans

• C: Risk cannot be ruled out Most psychotropic agents

• D: Positive evidence of risk in humans Valproic acid, Lithium

• X: Contraindicated in pregnancy

C. Risks of untreated psychiatric illness in the mother

• Poor compliance with prenatal care

• Risk of harm to mother and/or fetus

• ? Direct impact of illness on developing fetus (stress steroids)

• Risk of illness chronicity and treatment-refractoriness

D. Mood Stabilizers

• Lithium: 0.1% risk of Ebstein's and other cardiac anomalies

• Carbamazepine: 1% risk of neural tube defect, craniofacial abnormalities

• Valproic acid: 3-5% risk of neural tube defect

• Limited data on other mood stabilizers (gabapentin, lamotrigine)

E. Antidepressants

• Fluoxetine, TCAs: no increased risk of congenital malformation

• Inadequate information on other SSRIs, bupropion, MAOIs, mirtazapme

F. Anti-Psychotic Agents

• High-potency neuroleptics appear to be safe

• Avoid low-potency medications (increased risk of congenital malformation, fetal tachycardia)

• Inadequate data on atypical agents (olanzapine, clozapine, risperidone, quetiapine)

G. Benzodiazepines

• Slight increase in risk (0.6%) of cleft palate and lip (1^st trimester exposure)

• Lower doses may be used, PRN dosing to limk exposure

• Risk of neonatal toxicity: hypotonia, apnea

• Risk of neonatal withdrawal syndrome: seizure

H. Other medications

• Benztropine, diphenhydramine: limited data, use on a prn basis

• Stimulants: controversial (? premature delivery), avoid when possible 

• Buspirone: no data

• St. John's wort: no data on reproductive safety

I. Electroconvulsive Therapy (ECT)- rapid, safe and effective

J. Guideline for the use of psychotropic agents during pregnancy

• Make decisions on a case-by-case basis

• Optimize non-pharmacologic treatments

• Select medications with reproductive safety

• Minimize duration of exposure

• Minimize number of medications

• Use an effective dosage of medication

VI. Postpartum Psychiatric Illness

• The postpartum period is a time of increased risk for the emergence of psychiatric illness

• Some studies have demonstrated increased risk up to 1 year after delivery.

A. Definitions

1. DSM-IV: Postpartum Onset Specifier

• Episode emerging within 4 weeks of delivery

• Used to describe episode of major depression, bipolar (I or 11) disorder or brief psychotic disorder

• Marce Society: any episode emerging within one year after delivery

B. Three subtypes of mood disturbance or disorder

1. Postpartum Blues

• Affects 50-75% of women after delivery

• Within first two weeks

• Time-limited, lasting hours to days

• Characterized by mood lability, tearfulness, anxiety, insomnia

• No impairment of functioning

2.. Postpartum Depression

• Affects 10-15% of women after delivery

• Edinburgh Postnatal Depression Scale (EPDS) for screening

• Many women present with depressive symptoms during pregnancy

• Symptoms similar to non-puerperal MDD (dysphoria, tearfulness, insomnia, fatigue, anhedonia, suicidal ideation)

• Comorbid anxiety is common and may be severe

3. Postpartum Psychosis

• Rare, affecting 1 or 2 per 1000 pregnancies

• Early and dramatic onset, usually within the first 2 weeks

• Resembles an affective (manic) psychosis

• Symptoms include elated or dysphoric mood, restlessness or agitation, disorganized behavior, depersonalization, delusions or hallucinations

• Strong association with bipolar disorder

• High risk of suicide and infanticide

C. Risk Factors: Impossible to predict which women in the general population will develop postpartum psychiatric illness

1. Demographic Factors

• Parity, marital status, and socioeconomic status do NOT appear to influence risk for postpartum illness

• High rates of postpartum depression in teens (up to 25%)

2. Psychosocial Factors

• Marital discord

• Lack of support from spouse

• Recent adverse life event (divorce, death in family)

3. History of Psychiatric Illness

• Depression during pregnancy

• History of postpartum depression or psychosis (50-70% relapse) 

• History of bipolar disorder (30-50% relapse)

• History of recurrent major depression (up to 30% relapse)

4. Hormonal Factors

• No consistent differences in hormone levels (estrogen, progesterone, cortisol)

• Increased sensitivity to gonadal steroids?

D. Treatment

1. Postpartum Blues

• No specific treatment, support and reassurance

• If symptoms persist longer than 2 weeks, evaluation to rule out more significant mood disorder

2. Postpartum Depression: Treat with same intensity and duration as non-puerperal major depression

a. Non-pharmacologic treatment

• Psycho-education and Group Therapy

• Cognitive-Behavioral Therapy (focus on problem-solving) • Interpersonal Therapy (focus on relationships, support)

• Insight-Oriented Therapy: equivocal results

b. Pharmacologic treatment

• Antidepressants with demonstrated efficacy: fluoxetine, sertraline, venlafaxine

• Anxiolytic agents may be useful

c. Hormonal treatment

• Progesterone: inconsistent findings

• Estrogen (Gregoire et al): alone or as an adjunct to an antidepressant

3. Postpartum Psychosis

• Psychiatric emergency (inpatient treatment)

• Treat as an affective psychosis: neuroleptic, mood stabilizer, benzodiazepines

• ECT is rapid and effective

E. Postpartum Prophylaxis

• For women at high risk for postpartum psychiatric illness

• Li in women with history of postpartum psychosis or bipolar disorder

• Antidepressant prophylaxis in women with histories of depression?

VII. Breast-Feeding and Psychotropic Medications

• All psychotropic medications are secreted into the breast milk

• Concentrations in breast milk are variable

• No medication is safer than another

• Impact of trace amounts of medication on developing brain are not known

• Caution when breast-feeding premature infants (immature hepatic metabolism)

• Avoid breast feeding with mothers on lithium

VII. Menopause and Mood Disorders

• Increased incidence of depression during perimenopause

• History of major depression increase risk

• Impact of psychosocial factors on risk Poor physical health Inadequate social supports

• Some women more susceptible to fluxes in reproductive hormones (? association win PMS, postpartum depression)

• Hormone replacement therapy

Estrogen may have antidepressant efficacy

Improvement in cognitive functioning

VIII. Neurobiology of Estrogen

• Interacts with multiple neurotransmitter systems

• Increases norepinephrine synthesis

• Increases acetylcholine synthesis

• Increases serotonin levels

• Acts as an MAO inhibitor