The Reproductive Health Implications of Depression

Association of Reproductive Health Professionalswww.arhp.org

Expert Medical Advisory Committee

• Norma Jo Waxman, MD• Ellen Haller, MD• Ann Hutton, PhD, APRN • Kathy Besinque, PharmD

Learning Objectives

At the end of this session participants should be able to:• Recognize symptoms, risk factors and

presentations of depression in women, including pre-menstrual and post partum mood disorders

• Screen women for depression throughout their reproductive years

• Prescribe medications for depression in women and know when to refer

?Polling Question A

D. 75% of patients experience at least 1 recurrence following an initial diagnosis of depression.

?Question 1

Forms Of Depression In Women

• 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)

Greenberg PE, et al. J Clin Psychiatry. 2003

B. The risk of depression is highest for women aged 26 to 49.

?Question 2

Depression in Women: The Statistics

• Occurs in women double the rate in men▪ will affect 1 in 8 women ▪ 50% occurs between ages 25-44 years

• ~25% progress to chronic depression• Women at higher risk of recurrence and

more difficult to treat

American Psychiatric Association. 2000. Kessler RC, et al. Arch Gen Psychiatry. 2005. Noble RE. Metabolism. 2005. Rush AJ, et al. Psychiatr Ann. 2008.

Gender Differences

• Women have earlier onset of depression

• Episodes may last longer and recur more often

• More atypical symptoms• Suicide attempts more

frequent but less successful

• Less substance abuse than men

• More anxiety symptoms than men

• More associated eating disorders

• More associated migraine headaches

• More feelings of guilt• More seasonal

depression

MacArthur Initiative on Depression and Primary Care. 2009

Depression in Women: The Impact

• Leading cause of disability in women 15 to 44

• More likely to engage in high risk behaviors• Higher rates of co-morbid illness- obesity,

DM, CVD, pain• Significant economic burden: $83.1billion

(2000)• Non-adherence to therapy, diet, and exercise

Greenberg PE, et al. J Clin Psychiatry. 2003. Kessler RC, et al. JAMA. 2003. Patton SB, et al. J Affect Disord. 2009. World Health Organization. 2008.

?Polling Question B

Poorly 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• Women may be able to laugh and smile, w/o

obvious depressed mood- known as masked depression

• Universal screening is necessary

Risk Factors for Depression

• Family and/or personal history of mood disorders

• History of physical or sexual abuse• Loss of significant family member or friend• Chronic psychosocial stressors• Lack of an adequate support system• Relationship stress

Bhatia SC. Am Fam Physician.1999.

Suspect The Diagnosis:Clinical Presentation

• Multiple visits for vague complaints• Depressed voice, expression, or posture

• Pain syndromes: vulva, pelvic, vagina, menses, coitus, cystitis, GI, headache

• Clinician feels sad during or after visit

Rule Out Other Etiologies and Comorbid Conditions

• General medical illness Thyroid disease, anemia, diabetes, cancer

• Substance abuse and withdrawal• Medication side effects

Beta blockers, ACE inhibitors, GnRH analogues (Lupron) and Glucocorticoids

• Acute grief and mourning• Dysthymia, Bipolar disorder, PTSD, GAD,

Pies R. Manual of psychiatric therapeutics. 2003:240–69.

Two Question Screen for Depression

During the past month, have you been bothered by little interest or pleasure in doing things?

During the past months, have you often been feeling down, depressed, or hopeless?

Arroll B. BMJ 2003.

Validated screening tool with 97% sensitivity, 67% specificity

Depression Self-Assessment Instruments

Instrument NameNo. of Items

Brief Patient Health Questionnaire (PHQ-9) 9

Inventory of Depressive Symptomology, Self-Rated (QIDS-SR) 16

Beck Depression Inventory (BDI-I or BDI-II) 7-21

Zung Self-Rating Depression Scale 20

Center for Epidemiologic Studies Depression Rating Scale (CES-D) 20

Edinburgh Postnatal Depression Scale (EPDS) 10

Hackley, B, et al. J Midwifery Womens Health. 2010. Patton SB, et al. J Affect Disord. 2009.The MacArthur Initiative on Depression and Primary Care. 2009.

Brief Patient Health Questionnaire (PHQ-9)

MacArthur Initiative on Depression and Primary Care. 2009

D. All of the above are symptoms of depression according to DSM-IV diagnostic criteria.

?Question 3

DSM IV Criteria For Major Depression

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

• Symptoms must cause Significant distress Impair functioning

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR; 2000

DSM IV Criteria For Major Depression

• Symptoms not caused by A substance A general medical condition Bereavement

• Symptoms are not accompanied by mania

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR; 2000

DSM IV Criteria For Major Depression

• 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

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR; 2000

Assessment of Suicide Risk

• 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?"

Assessment of Suicide Risk

• 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?”

• If they can not contract to not harm themselves, call 911 or the police, have patient transported for evaluation

Depression Management• Mild Depression

▪ Medication no better than placebo• Moderate- Severe Depression

▪ Offer medication with or w/o therapy▪ Therapy seems to provide protection

against relapse or recurrence▪ 90% who have had 3 episodes will have

recurrence w/o lifelong pharmacotherapy

National Institute for Health and Clinical Excellence- Clinical guidelines CG90, TMAP Guidelines, The MacArthur Initiative on Depression and Primary Care. 2009.

Cognitive Behavioral Therapy Alone or With Antidepressants

Miranda J, et al. JAMA. 2003. Parikh SV, et al. J Affect Disord. 2009. The MacArthur Initiative on Depression and Primary Care. 2009.

Interpersonal Therapy Alone or With Antidepressants

International Society for Interpersonal Psychotherapy. 2011. Parikh SV, et al. J Affect Disord. 2009. The MacArthur Initiative on Depression and Primary Care. 2009.

Medication Treatment Guidelines

• 50% have effect in 2 weeks Optimal effect may take 4-6 weeks

• Titrate to achieve therapeutic dose• Serial administration of validated scale• 50% decrease in symptoms predictive of

remission• Treat for 6-12 months after remission• 65-70% response to first antidepressant

MacArthur Initiative on Depression and Primary Care. 2009.

Partial Or No Response

• Effect should be present by 6 weeks• Assess for adherence to daily dosing • Re-evaluate diagnosis:

Other psychiatric disorders or sub abuse Organic disorder

• Partial response- augment with different medication class or increase dose

• No Response- change to different medication class

C. Fluoxetine is an approved medication for the treatment of depression associated with a higher risk of drug interactions.

?Question 4

SSRI 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)

Discontinuation Syndrome

• Abrupt discontinuation of SSRIs can lead to dizziness, nausea, lethargy, headache, anxiety, and agitation

• Medications with short half-lives more likely to trigger withdrawal symptoms when abruptly discontinued

• Do not prescribe SSRIs with short half-life to women who may have difficulty with adherence

• Counsel that medications be tapered slowly

Ferguson JM. Prim Care Companion J Clin Psychiatry 2001.

Complementary and Alternative Medicine Therapy for Depression• Commonly used and often not revealed• St. John’s Wort for mild-moderate depression

▪ Studies conflicting▪ Drug-drug interactions including hormonal

contraception, SSRIs and coumadin▪ Most guidelines discourage use

• Light therapy for seasonal affective disorder• Exercise as adjunct• No benefit in RCTs

▪ Accupuncture and Omega-3 fatty acids

Ravindran AV, et al. J Affect Disord. 2009. Cochrane Review, 2009. Freeman, M P et al. 2010. Complementary and alternative medicine in MDD: APA Task Force Report. J Clin Psy 2010.

Side effects of SSRIs and SNRIs

• All SSRIs and SNRIs effectively treat anxiety disorders

• Symptoms that usually resolve quickly▪ Headache▪ Nausea- Sertraline worse▪ Sleeplessness or drowsiness▪ Agitation- Fluoxetine> Sertraline> Paroxetine

• Anticholinergic effects• Decreased libido and/or delayed orgasm

▪ SNRIs have less sexual side effects ▪ Buproprion can be added or substituted

MacArthur Initiative on Depression and Primary Care. 2009.

Follow-up Schedule After Initial Management

Symptoms Frequency

Minor Watchful waiting; re-evaluate 4-8 weeks

Mild MDD Visit or phone contact every month

Moderate MDD Visit or phone contact every 2-4 weeks

Severe MDDVisit or phone contact every

few weeks until PHQ-9 improves ≥ 5 points

Lam RW, et al. J Affect Disord. 2009. The MacArthur Initiative on Depression and Primary Care. 2009.

B. Mirtazapine is an approved medication for the treatment of depression associated with weight gain.

?Question 5

Stacey

• 22 yo, college graduate• Single, unemployed• Annual exam• 10 pound weight gain• Reports feeling irritable, periods of crying,

overwhelmed, severe fatigue, bloated and increased appetite with symptom onset 1 week before period and resolution within 3 days after onset of menses since high school

Premenstrual Syndrome (PMS)

• PMS common and mild: affects 50-80%• ACOG diagnostic criteria

At least 1 moderate to severe physical symptom At least 1 psychological symptom

• Symptoms start ~5 days before menses• Symptom resolution by end of menstrual flow• Cyclic, not required every cycle

American College of Obstetricians and Gynecologists, 2000.

Premenstrual Dysphoric Disorder (PMDD)

• PMDD rare and severe- affects 2% to 10%• Must occur every cycle and impede function• Requires 2 cycle diary documentation

Luteal phase symptom pattern Resolution with the onset of menses

American Psychiatric Association, 2000.

Premenstrual Dysphoric Disorder (PMDD)

• DSM-IV diagnostic criteria ▪ Absence of symptoms during follicular phase

≥ 1 core of the following symptoms:▫ Markedly depressed mood▫ Anxiety or tension▫ Affective lability▫ Persistent anger or irritability

Premenstrual dysphoric disorder. DSM4 : American Psychiatric Association, 2000

Premenstrual Dysphoric Disorder (PMDD)

• DSM-IV diagnostic criteria (cont)▪ Plus any of the following symptoms to total ≥ 5:

▫ Decreased interest in usual activities (anhedonia)▫ Poor concentration▫ Lethargy▫ Change in appetite▫ Sleep disturbances▫ Feeling overwhelmed▫ Physical symptoms, i.e. breast tenderness,

headaches, “bloated”, muscle pain

Premenstrual dysphoric disorder. DSM4 : American Psychiatric Association, 2000: 771–774.

Premenstrual Dysphoric Disorder (PMDD): Treatment

Jarvis CI, et al. Ann Pharmacother. 2008.

Stacey-PMDD

• Treatment: Obtain menstrual cycle diaries x 3 Rx: drospirenone/ethinyl estradiol Recommend regular exercise

• Follow up: 2 month follow-up indicates most symptoms

improving Able to go to class Still has some bloating with placebo pills Suggestions?

Aiko

• 51 yo, married real estate agent• 2 adult children• Reports horrible hot flashes which started 6 months ago• Insomnia• Smoker, BP 127/84• BMI 32, HDL 55, LDL 126• Scores 17 on PHQ-9

more…

Depression and Peri-menopause

• Risk of depression OR 2.50 to pre-menopause• Randomized longitudinal cohort study showed individual

increased variability of estradiol strongest risk factor of new dx of depressive disorder. OR> 2.45

• Mood changes during perimenopause most common reason women seek care and of those who seek care:▪ ~50% are clinically depressed ▪ >33% have 1st depressive episode

• Most common symptoms include: Mood changes Sleep disturbances

Freeman EW, et al. Arch Gen Psychiatry. 2006.Parry BL. Intl J Womens Health. 2010. Steinberg EM, et al. J Clin Psychiatry. 2008.

Symptoms of Perimenopausal Depression

Banger M. Maturitas. 2002. Parry BL. Intl J Womens Health. 2010. Steinberg EM, et al. J Clin Psychiatry. 2008.

Aiko-Perimenopause

• Treatment:▪ Venlafaxine 37.5 mg, increasing to 75 mg after 4 weeks▪ Transdermal HRT initiated after discussion of risks and benefits

• Follow Up:▪ PHQ-9 score of 11▪ Less irritable, improved concentration▪ Hot flashes slowly improving▪ Increased Venlafaxine to 150 mg

Provider Resources

• MacArthur Initiative on Depression in Primary Care▪ http://www.depression-primarycare.org/

• American Psychiatric Association▪ http://www.healthyminds.org/

• Cox, J.L., Holden, J.M., and Sagovsky, R. 1987. Detection of postnatal depression: Development of the 10-item Edinburgh Postnatal Depression Scale.

Provider and Patient Resources

• National Institute of Mental Health▪ http://

www.nimh.nih.gov/health/publications/women-and-depression-discovering-hope/index.shtml

• WomensHealth.gov• http://www.womenshealth.gov/faq/depression-

pregnancy.cfm• Mayo Clinic

• http://www.mayoclinic.com/health/depression/MH00035

Provider and Patient Resources

• Healthy Place▪ http://www.healthyplace.com/depression/women/

depression-in-women/menu-id-68/. • Massachusetts General Hospital Center for

Women’s Mental Health▪ http://www.womensmentalhealth.org/.