Depressive Disorders in Women

Depressive Disorders in Depressive Disorders in WomenWomen

Women’s Health ConferenceWomen’s Health ConferenceOrlando, Florida March 2011Orlando, Florida March 2011Norma Jo Waxman MDNorma Jo Waxman MDAssociate Professor of Family and Community MedicineAssociate Professor of Family and Community MedicineFaculty, The Bixby Center for Global Reproductive HealthFaculty, The Bixby Center for Global Reproductive HealthUniversity of California San FranciscoUniversity of California San [email protected]@fcm.ucsf.edu

ObjectivesObjectives

At the end of the talk participants will be able to: Describe the range of Mood Disorders women

experience Recognize post partum mood disorders Prescribe medications for depression in women

and know when to refer

Mood Disorders Mood Disorders = Affective Disorders

• Disturbance in mood • Inappropriate, exaggerated, or limited range of

feelings • Everybody gets down, and everybody

experiences excitement and pleasure • Mood disorder: feelings are extreme • Crying, and/or feeling depressed, suicidal • Or excessive energy, sleep not needed for days

and decision making significantly hindered

Common DiseaseCommon Disease

• 10% of primary care adult patients

• 3x visits as non-depressed patients

• Occurs in all demographic groups

• Occurs in women double the rate in men– 20% lifetime incidence– 50% occurs between ages 25-44 years

• Common cause of slow recovery from physical illness

Precipitating EventsPrecipitating Events

Life events which can precipitate depression • Loss of a parent or sibling in early childhood • Loss of a limb or another part of the body

(mastectomy) • domestic violence • miscarriage • loss of self-esteem • divorce or separation

Depression and DisabilityDepression and Disability

• More disability days than any other chronic condition except coronary artery disease

• More chronic pain than any other chronic disease except arthritis

• WHO: 2nd most important cause worldwide of life years lost to disability (2020)

• $31.3 billion/year in the United States (1990)

Poorly Recognized and TreatedPoorly Recognized and Treated• Under-recognized

– 80% of patients are undiagnosed– Only 20% of patients receive treatment– 80% of patients respond to treatment

• Anxiety often due to depression

• Patient may present with smiling or able to laugh, w/o obvious depressed mood- known as masked depression

• Universal screening is necessary

Barriers to Diagnosis:Barriers to Diagnosis: Clinician Clinician

Failure to recognize somatization

Distinguishing sadness from depression

Discomfort with emotional issues

Misdiagnose as organic or hormone related

Concern that assessment is time-consuming

Difficulties in obtaining a referral

Barriers To DiagnosisBarriers To Diagnosis: : PatientsPatients

Resistance to diagnosis of a mental disorder

Belief it is natural to be depressed sometimes

Belief they can will themselves well Shame Cultural Issues

Suspect The Diagnosis:Suspect The Diagnosis: Clinical PresentationClinical Presentation

Multiple visits for vague complaints

Depressed voice, expression, or posture

Pain syndromes: vulva, pelvic, vagina, menses, coitus, urinary tract

Clinician feels sad during or after visit

Forms Of Depression In Forms Of Depression In WomenWomen

• Unipolar forms– Major depressive disorder– Chronic depression (dysthymia)

• Bipolar mood disorder (manic-depression)• Other distinct syndromes in women

– Eating disorders– Premenstrual dysphoric disorder (PMDD)– Postpartum mood disorders

• Grief, adjustment reactions (minor depression)

Less Common Variants of DepressionLess Common Variants of Depression

• Agitated depression: – agitation severe, common in middle-aged & elderly

• Atypical depression: – severe anxiety, severe fatigue, increased sleep &

increased appetite. Often medication resistant

• Seasonal affective disorder (SAD): – depression same time of the year, usually winter

Mood Disorders: PrevalenceMood Disorders: Prevalence

Disorders

Major Depression

Dysthymia

Bipolar I

Bipolar II

PMDD

MDD (Postpartum)

Prevalence

4.9%

3.2%

0.8%

0.5%

5.0%

13%

Levels of Unipolar DepressionLevels of Unipolar Depression

• Major depressive disorder– Mild: extra effort in ADL*– Moderate: often prevents ADL*– Severe: always prevents ADL*

• Chronic depression = dysthymia

*ADL: activities of daily living*ADL: activities of daily living

Major Depression DisorderMajor Depression Disorder

MDD, Single episode• Absence of mania or

hypomania

MDD, Recurrent• 2 major depression

episodes, separated by at least a 2 month period with more or less normal functioning/mood

DSM IV Criteria For Major DSM IV Criteria For Major DepressionDepression

• At least five of nine symptoms– Depressed mood and/or anhedonia (required)– Low self-esteem (worthlessness)– Sleep disturbance– Change in appetite or weight– Difficulty concentrating– Fatigue, loss of energy– Psychomotor agitation or retardation– Recurrent thoughts of death or suicide

DSM IV Criteria For Major DSM IV Criteria For Major DepressionDepression

• Clinically significant distress or impairment in social, occupational, or other areas of function

• Not due solely to physical health condition, prescribed medication, or substance abuse

• Symptoms not accounted by bereavement; or:– Persist longer than two months– Marked functional impairment– Suicidal ideas– Psychosis; psychomotor retardation

Criteria For Major DepressionCriteria For Major Depression

• Symptoms should be present– Most days– Most of the day– For at least 2 weeks

Screening With 2 QuestionsScreening With 2 Questions

• Depression is present if 1 or both present:“In the past month have you been often

bothered by. . . . . . depressed mood?”

. . . lack of interest or pleasure?”

Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments for depression: Two questions are as good as many. J Gen Int Med 1997;12:439-445.

Direct Questions to AskDirect Questions to Ask

Depressed mood "How's your mood been lately?"

Anhedonia– Loss of interest or pleasure– Lack of enjoyment in most daily activities "What have you enjoyed doing lately?" "Are you getting less pleasure in things you typically enjoy?"

Direct Questions to AskDirect Questions to Ask

• Other symptoms"Have you been feeling down on

yourself?"

"How are you eating; sleeping?”

"How's your energy level?"

"Do you ever feel like life is not worth living?"

"How's your concentration?"

Mnemonic: Mnemonic: “Space Drags”“Space Drags”

S leep disturbance

P leasure/interest (lack of)

A gitation

C oncentration

E nergy (lack of)/fatigue

D epressed mood

R etardation movement

A ppetite disturbance

G uilt, worthless, useless

S uicidal thought

Criteria For Dysthymia or Criteria For Dysthymia or Chronic DepressionChronic Depression

• Dysthymia– 2 years depressed mood most days– With 2 or more symptoms of depression– A major depressive episode has not

occurred• Treatment

– Same as for depression

Rule Out Other EtiologiesRule Out Other Etiologies

• General medical illness– hypo or hyperthyroidism, anemia, diabetes,

multiple sclerosis

• Substance abuse• Medication side effects

– Beta blockers, ACE inhibitors, – GnRH analogues (Lupron)– Glucocorticoids– Amphetamine withdrawal

• Acute grief and mourning

Suicidal AssessmentSuicidal Assessment

• Screen every patient suspected of depression

• Asking does not insult patient or initiate thought

• Ask direct questions: "Have you had thoughts of hurting yourself?"

"Do you sometimes wish your life was over?"

"Have you had thoughts of ending your life?"

Suicidal AssessmentSuicidal Assessment

• If yes, assess immediate risk:

"Do you feel that way now?”

"Do you have a plan?"

"Do you have the means to carry out your plan?”

"Do you promise to call me immediately if your suicidal thoughts get stronger?”

Treatment Of Major Treatment Of Major DepressionDepression

• Components

– Psychotherapy

– Psychopharmacotherapy

– Psychosocial interventions

– ECT (2nd line or life-threatening)

• Alone or in combination

Bipolar DisordersBipolar Disorders

• Bipolar I Disorder

• Bipolar II Disorder

• Cyclothymic Disorder

Manic Episode: Diagnostic CriteriaManic Episode: Diagnostic Criteria

A period of abnormally and persistently elevated, expansive, or irritable mood not due to psychosis, meds or organic etiology with marked impairment

Plus 3 of the following 7 symptoms:• Inflated self esteem or grandiosity• Decreased need for sleep• More talkative than usual or pressure to keep talking• Flight of ideas, or racing thoughts• Distractibility• Increase in goal directed activity• Excessive involvement in pleasurable activities

Hypomania: Diagnostic CriteriaHypomania: Diagnostic Criteria

• All the criteria of a Manic episode except without marked impairment

Bipolar DisorderBipolar Disorder

Bipolar I• Alternation of full

manic and depressive episodes

• Average onset is 18 years

• Tends to be chronic• High risk for suicide

Bipolar II• Alternation of Major

Depression with hypomania

• Average onset is 22 years

• Tends to be chronic• 10% progess to full

biploar I disorder

CyclothymiaCyclothymia

A. Many hypomanic episodes and periods with depressed mood not meeting criteria of Major Depression, and lasting 2 years

B. During 2 yr period of disturbance, never without hypomanic or depressive symptoms more than 2 months at a time

C. No evidence of MDD or Manic episode during the first two years of disturbance

Depression: GeneticsDepression: Genetics

Family studies:

• Relatives 2-3x more likely to have a mood disorder (usually major depression)

Twin studies:

• Identical 3x more likely than fraternal twin to have a mood disorder (particularly for bipolar disorder)

Women: Heritability rates are higher

Grief ReactionsGrief Reactions

• May last up to 2 years after loss or event

• Usually falls short of criteria for major depression

• Rarely causes prolonged impairment in work and other activities

• Cyclicity is common in days, weeks, months

• If functional impairment, Rx with SSRI’s for 30 days

Premenstrual Dysphoric Premenstrual Dysphoric DisorderDisorder

• 5% of women, typical age 18-30 years• Symptoms last 5-14 days in the luteal phase• Must abate at onset of menses• Symptoms: depression, anxiety, emotional lability, tension, irritability, anger, sleep and appetite disturbances• Rx with daily or luteal phase SSRIs• Role of OCs with drospirenone

Pearlstein T. Drugs 2002;62:1869-85.Pearlstein T. Drugs 2002;62:1869-85.

Chronic Pelvic Pain and Chronic Pelvic Pain and DepressionDepression

• Offer antidepressant early in evaluation

• Offer neuropathic drug(s) early in evaluation

• Offer NSAID analgesics early in evaluation

• Offer early referral to mental health provider for help with depression and developing coping skills

Postpartum Mood DisordersPostpartum Mood Disorders

Prevalence Onset Duration Treatment

Blues 50-80% 1-5 days <2 weeks Reassurance

Depression 10% 2wk - 1 year

3-14 mo Medication or psychotherapy

Psychosis 0.1-0.2% 2 days to 1 month

Variable Medication, hospitalization

Post-partum DepressionPost-partum Depression

• 1 of 10 women experience post-partum depression, but the condition is under-diagnosed

• May have significant impact on both mother and child

• Societal pressures to be “good mother” may prevent woman from admitting symptoms

““Baby Blues”Baby Blues”

• Occurs in 70-85% of women• Onset within the first few days after

delivery• Resolves by 2 weeks• Symptoms include: mild depression,

irritability, tearfulness, fatigue, anxiety• May have increased risk of post-partum

major depression later on

Post-partum Major DepressionPost-partum Major Depression

• Symptoms of depression that last longer than 2 weeks

• Usually begins 2-3 weeks after delivery

• May start and last up to one year

• High risk of recurrence in future pregnancies

Treatment for Post Partum Treatment for Post Partum DepressionDepression

• Same as for major depression

• SSRI’s work well

• All antidepressants are to some degree, excreted in the breast milk, but usually undetectable levels in the infant’s blood

• Avoid Prozac due to long half life- may accumulate in the infant

Treatment Of Mood DisordersTreatment Of Mood Disorders

• Components

– Psychotherapy

– Psychopharmacotherapy

– Psychosocial interventions

– ECT (2nd line or life-threatening for MDD)

• Alone or in combination

Medications Treatment Medications Treatment GuidelinesGuidelines

• 50% have effect in 2 weeks• Optimal effect may take 4-6 weeks• Titrate to achieve therapeutic dose• If no response by 6 wks, switch

agents• If partial response at maximum dose,

augment with 2nd drug or get consult • Treat for 6-12 months• 65-70% response to first anti-

depressant

Partial Or No ResponsePartial Or No Response

• Effect should be present by 6 weeks

• Assess for adherence to daily dosing

• Re-evaluate diagnosis:– Other psychiatric disorders– Substance abuse– Organic disorder

• Adjust dosage or change medication

• Refer to a psychiatrist

Daily Dosing Of SSRI’sDaily Dosing Of SSRI’s

Medication name

Brand name

Start Range Maximum

Citalopram CelexaR 10 mg 10-40 mg 60 mg

Escitalopram LexaproR 5 mg 5-10 mg 20 mg

Fluoxetine ProzacR 10 mg 10-40 mg 80 mg

Paroxetine PaxilR 10 mg 10-40 mg 60 mg

Sertraline ZoloftR 25 mg 50-100 mg 300 mg

NEWER AGENTSNEWER AGENTS

• SNRIs = serotonin noradrenergic reuptake

inhibitor– Desvenlafaxime PristiqR

– Venlafaxine Generic, Effexor/ Effexor XRR,

– Duloxetine CymbaltaR

• Other antidepressants– Bupropion WellbutrinR /SR /XL, Aplenzin™ – Mirtazepine RemeronR

– Nefazodone SerzoneR- Hepatic– Trazadone DesyrelR

BuproprionBuproprion (Wellbutrin IR,SR,XL (Wellbutrin IR,SR,XLR)R)

• Does not cause sexual dysfunction

• Useful as first line or to augment SSRI/SNRI

– Start 150mg qd for 1 wk, increase to 150mg bid

– Do not exceed 200mg single dose

– Maximum dosing = 400mg / day

– Avoid use if risk of seizures

Medication Side EffectsMedication Side Effects

• Agitation/insomnia: – ProzacR > ZoloftR > PaxilR > Tricyclics >

RemeronR

– Add sedative or hypnotic

• Gastrointestinal distress– Don’t use Setraline (Zoloft)– Take medication after meals

• Sedation– Take medication at bedtime

Medication Side EffectsMedication Side Effects

• Anticholinergic effects– Hydration– Add bulk/ fiber to diet, hard candy– Stool softener

• Postural hypotension– Hydration– Change positions slowly– Support hose

• Sexual dysfunction (worse with SSRIs)– Add or Switch to buproprion

SSRI Drug InteractionsSSRI Drug Interactions

• Paroxetine = Fluoxetine > Sertraline > Citalopram= Escitalopram in P450 inhibition

• Common interactions

– Some anti-hypertensive levels may increase (beta-blockers and Ca channel blockers)

– May increase digoxin levels

– May increase levels of anticonvulsants such as carbamazepine (Tegretol) and phenytoin (Dilantin)

Does Hormonal Contraception Does Hormonal Contraception Cause or Worsen Depression?Cause or Worsen Depression?

• Older studies suggested progestins could – Make pre-existing depression worse– Cause depression in a small % of users– “More likely” with progestin-only methods

• Newer (and better) studies show that neither of these assertions are correct

• 2010 CDC Medical Eligibility Criteria (MEC):– In depressed women, all methods are

categorized as US MEC 1

Depression In PregnancyDepression In Pregnancy

• Include the patient in decision-making– Overall well-being & Ability to function– Weigh risks and benefits

• Untreated depression in pregnancy leads to increased risk of postpartum depression

• One study found both SSRIs & untreated depression associated with preterm birth

Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Wisner KL - Am J Psychiatry - 2009; 166(5): 557-66 Treatment of Mood Disorders During Pregnancy and Postpartum Cohen et al 2010; 33(2): 273-293

Safety Of Drugs In PregnancySafety Of Drugs In Pregnancy

• Fluoxetine best studied SSRI for safety and efficacy in pregnancy and lactation. >1500 in-utero exposures have been reported w/o evidence of teratogenicity Avoid Paroxetine

• SSRIs and SNRIs are category C

• Wellbutrin is category B

• 2005 meta-analysis of prospective comparative studies found no increased risk of anomalies

Einarson TR - Pharmacoepidemiol Drug Saf - 01-DEC-2005; 14(12): 823-7

Safety Of Drugs: LactationSafety Of Drugs: Lactation

• Pregnant and lactating women excluded from controlled trials of new drugs

• SSRI’s and bupropion present in breast milk– Limited data on newborn impact– No findings of effect on growth or development

• Include the patient in decision-making

SSRI DiscontinuationSSRI Discontinuation

• Somatic and psychological symptoms– Disequilibrium, gastrointestinal symptoms,

flu-like symptoms, sensory disturbances, anxiety, irritability

• Onset 1-3 days after stopping Rx, last an average of 10 days, usually mild and transient

• Case reports of severe discontinuation symptoms• PaxilR and ZoloftR > ProzacR (shorter half-life)• Noncompliance leads to discontinuation

symptoms• Avoid by tapering drug in weekly increments

HerbalsHerbals

• St John's wort (hypericum perforatum):

– mild antidepressant, sedation, anxiolysis

– headache most common side effect

– Many studies show induction of CYP450

– Does decrease efficacy of estrogen based contraception

Follow UpFollow Up

• Phone call in 3 days to assess side effects

• 1,2 or 4 weeks according to severity– Phone can be used to titrate dose– Use flow sheet to score symptoms

• Remission = normal psychosocial functioning

• Maintain effective dose for 6-12 months

• Consider role of prophylactic maintenance Rx if current episode is a relapse

Office InterventionsOffice Interventions

Assess for adverse personal relationships

Assess family and community support

Consider self-help groups

Pursue watchful waiting with periodic follow up

SuicideSuicide

• 8th leading cause of death in the U.S.• Overwhelmingly white phenomena• Suicide also high in Native Americans• Rate of suicide is increasing in

adolescents and elderly• Males are more likely to commit suicide• Females are more likely to attempt suicide

5 Myths and Facts About 5 Myths and Facts About SuicideSuicide

Myth #1:• People who talk about

killing themselves rarely commit suicide.

Fact:• Most people who

commit suicide have given some verbal clues or warnings of their intentions


Myth #2:• The suicidal person

wants to die and feels there is no turning back.

Fact:• Suicidal people are

usually ambivalent about dying; they may desperately want to live but can not see alternatives to problems.


Myth # 3:• If you ask someone

about their suicidal intentions, you will only encourage them to kill themselves.

Fact:• The opposite is true.

Asking lowers their anxiety and helps deter suicidal behavior. Discussion of suicidal feelings allow for accurate risk assessment.


Myth # 4:• All suicidal people are

deeply depressed.

Fact:• Although depression

is usually associated with depression, not all suicidal people are obviously depressed. Once they make the decision, they may appear happier/carefree.


Myths # 5:• Suicidal people rarely

seek medical attention.

Fact:• 75% of suicidal

individuals will visit a physician within the month before they kill themselves.

ConclusionsConclusions

• Depression is a chronic, recurrent disease• Depression is common in women• Many women suffer needlessly because their

depression is not diagnosed and treated • Diagnosing depression is straightforward• Antidepressant treatment is effective and

practical• Primary care providers should be able to

recognize and treat depression in women

Mild depressive disorderMild depressive disorder• Complains of low mood, lack of energy & enjoyment

and poor sleep.• Other symptoms include anxiety, phobia &

obsessional symptoms.• Sleep disturbance often difficult to fall asleep,

restless with period of waking during the night followed by sound sleep before waking.

• Mood may vary during the day; worse in the evening than in the morning in contrast to more severe cases.

• Biological features uncommon.

Moderately severe depressiveModerately severe depressive disorderdisorder

• Appearance-sad appearance & psychomotor retardation • Low mood-misery, worse in the morning & irritability and

agitation.• Lack of interest & enjoyment-reduced energy, poor

concentration & memory.• Depressive thinking-pessimistic & guilty thoughts, self-

blame, suicidal ideas & hypochondriacal ideas.• Biological symptoms-early wakening, weight loss

reduced appetite& reduced sexual drive.• Other symptoms-obsessional symptoms,

depersonalization etc.

Severe depressive disorderSevere depressive disorder• All the features described under moderate depressive

disorder occur with greater intensity.• There may be additional symptoms; namely delusions &

hallucinations ( psychotic depression ). • Delusion namely; worthlessness, guilt, ill-health, poverty,

hypochodriacal delusions, delusion of impoverishment, nihilistic delusions & delusion of persecution.

• Perceptual disturbances; fall short of hallucinations but few experience true hallucinations usually auditory.

• Suicidal ideas & rarely homicidal ideas

Depressive Disorders in Women

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