The Reproductive Health
Implications of Depression
Association of Reproductive Health
Professionals
www.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
Question 1
D. 75% of patients experience at least 1
recurrence following an initial diagnosis of
depression.
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
Question 2
B. The risk of depression is highest for women
aged 26 to 49.
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?
Validated screening tool with
97% sensitivity, 67% specificity
Arroll B. BMJ 2003.
Depression Self-Assessment
Instruments
Instrument Name
Brief Patient Health Questionnaire (PHQ-9)
Inventory of Depressive Symptomology, SelfRated (QIDS-SR)
Beck Depression Inventory (BDI-I or BDI-II)
Zung Self-Rating Depression Scale
Center for Epidemiologic Studies Depression
Rating Scale (CES-D)
Edinburgh Postnatal Depression Scale (EPDS)
No. of
Items
9
16
7-21
20
20
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
Question 3
D. All of the above are symptoms of
depression according to DSM-IV diagnostic
criteria.
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 DSMIV-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
Question 4
C. Fluoxetine is an approved medication for
the treatment of depression associated with
a higher risk of drug interactions.
SSRI Drug Interactions
• Paroxetine = Fluoxetine > Sertraline >
Citalopram= Escitalopram in P450 inhibition
• Common interactions
 Some anti-hypertensive levels may increase (betablockers 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 MDD
Visit 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.
Question 5
B. Mirtazapine is an approved medication for
the treatment of depression associated with
weight gain.
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/wome
n-and-depression-discovering-hope/index.shtml
• WomensHealth.gov
•
http://www.womenshealth.gov/faq/depressionpregnancy.cfm
• Mayo Clinic
•
http://www.mayoclinic.com/health/depression/MH
00035
Provider and Patient Resources
• Healthy Place
▪
http://www.healthyplace.com/depression/women/d
epression-in-women/menu-id-68/.
• Massachusetts General Hospital Center for
Women’s Mental Health
▪
http://www.womensmentalhealth.org/.