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Depression in Women
Depression is a common and potentially devastating mood disorder affecting an individual’s persistent emotional state and diminishing function and quality of life. Only approximately half of individuals with mood disorders undergo treatment, with only 38.5% of those thought to be treated adequately.1 The estimated annual economic costs of depression are in the billions of dollars.2
The National Institute of Mental Health (NIMH) defines several forms of depression as shown in Table 1.3 Psychotic depression, seasonal affective disorder, and bipolar disorder will not be addressed here.
Table 1. Depressive Disorders and Their Characteristics
|Bipolar disorder (previously referred to as manic-depressive illness)||Periods of depression with periods of mania|
|Dysthymic disorder||Symptoms persisting 2 years or greater that prevent normal functioning or feeling well, but may not be severe enough to cause disability|
|Major depressive disorder||Symptoms that interfere with the ability to work, sleep, eat, and enjoy activities previously considered pleasurable|
|Postpartum depression||Major depressive episode that occurs within 1 month after deliverya|
|Psychotic depression||Severe depression accompanied by a type of psychosis (eg, hallucinations, delusions)|
|Seasonal affective disorder||Depressive illness that typically occurs in winter when exposure to natural sunlight is less than in other seasons|
aThe DSM-5 Work Group is proposing to expand this to within 6 months after delivery. Information from National Institute of Mental Health: Depression. Available at http://www.nimh.nih.gov/health/publications/depression/complete-index.shtml.
Estimates of the prevalence of depression in the primary care setting range from 6% to 9%, placing it among the top 10 diagnoses made by the family physician.2 In pregnancy, some type of depression occurs in 8.5% to 11% of women, with major depressive disorder (MDD) occurring in 3% to 5% of these women.6
During the first postpartum year, 6% to 13% of women have some type of depression.7 Postpartum blues, which occurs in up to 80% of women, is distinguished from depression by shorter duration (less than 10 days), earlier onset following delivery (within 2 to 3 days), and mild dysfunction without suicidal ideation.
Among women with a major affective disorder, the risk of an MDD episode is increased in the postpartum period (30%) and during the menopausal transition (5-fold).8,9
Etiology and Risk Factors
Investigators using data from a large general practice prospective cohort from seven countries (n = 10,045) found that most depression risk factors (eg, substance abuse, life stressors) are more common in women and have a greater effect in women than in men on MDD risk.18
Table 2. Risk Factors for MDD in Women Across the Life Cycle and for Suicide Completion
|Pregnancy||Postpartum||Midlife||Risk Factors for Suicide Completion|
|Antenatal depressive symptoms||History of MDD||Physical health role limitations||Absence of children|
|Family history of postpartum major depression||Financial problems||Prior anxiety disorder||Chronic pain|
|MDD in prior pregnancy||Past-year stressful life event||Recent stressful life event||Chronic physical illness|
|History of MDD||Relationship problems||Family history of suicide|
|Poor social support||Unplanned/unwanted pregnancy||Homelessness|
|Stressful life event during pregnancy||Older age (
|Poor social support|
|Younger age (teenager)|
Information from references 1, 12-17, 27.
If screening is undertaken, using the first two questions (Table 3) of the Patient Health Questionnaire-9 (PHQ-9) (available at http://www.phqscreeners.com) appears to be effective at identifying patients with possible depression.22 Because there is no best screening tool, a method should be chosen based on personal preference, the patient population served, and the practice setting.
Table 3. Two-Question Screenera for Depression
|Question||Not at all||Several days||More than half of days||Nearly every day|
|Over the past 2 weeks, how often have you been bothered by feeling down, depressed, or hopeless?||0||1||2||3|
|Over the past 2 weeks, how often have you been bothered by feeling little interest or pleasure in doing things?||0||1||2||3|
In an Australian primary care study, a score of 2 or greater was found to occur in 26% of the population and had a sensitivity of 86%, specificity of 78%, positive likelihood ratio of 4.0, and negative likelihood ratio of 0.18 for major depression.38 A score of 3 or greater occurring in 11.3% of the population had a sensitivity of 61%, specificity of 92%, positive likelihood ratio of 7.7, and negative likelihood ratio of 0.42 for major depression. These questions can also be scored as yes or no, where a yes answer to either question is considered a positive result.
Diagnosis and Clinical Assessment
A screen with a positive result for depression should trigger a full diagnostic interview using the DSM-IV-TR criteria to determine the presence or absence of a specific depressive or dysthymic disorder. The two criteria for major depression are that it must interfere with function (eg, work, school, relationships, social life), and it must not be due to another medical or psychiatric disorder.
Important aspects of the history, physical examination, and laboratory tests are shown in Table 4. Because depressive symptoms can fluctuate with hormonal cycles, ask about mood changes across the reproductive life (eg, menstruation, pregnancy, birth control including oral contraceptive use, abortion, menopause).25,26
Table 4. Key Features of Clinical Assessment in Patients with Depression
|Feature or Test||Purpose|
|Medication history||Antihypertensives, steroids, gastrointestinal drugs, psychotropic drugs, and antihistamines, among others, can cause depression|
|Substance abuse||Alcohol, cocaine, and amphetamines are associated factors and require specific management|
|Psychiatric history||Previous episodes of affective disorder and drugs used and responses|
|Recent medical conditions||Serious physically restricting heart disease, diabetes, multiple sclerosis, and thyroid disease can cause depression and affect treatment decisions|
|Eating disorders and other psychiatric conditions||These conditions may coexist with depression and require additional treatment considerations|
|Family history of psychiatric disorders||Common; recurrent MDD in a close family member increases the likelihood of recurrent episodes in the patient|
|Current personal stressors||Increase risk and may be best addressed through psychotherapy|
|Premenstrual symptoms||In premenstrual dysphoric disorder, symptoms occur during the last week of the luteal phase in most menstrual cycles during the past yeara|
|Physical appearance||Clues to depression in depressed appearance and lack of personal hygiene|
|Mental status examination||Confusion may occur in depression and affects treatment considerations|
|Comorbid illness||Optimizing management may alleviate depressive symptoms, and outcomes of many conditions are worsened by depression|
|Laboratory Tests (not needed in every patient)|
|TSH||Hypothyroidism symptoms can mimic those of depression and are common postpartum (8% develop postpartum autoimmune thyroiditis) and in older adults|
|Hematocrit||Anemia symptoms can mimic those of depression|
|Vitamin B12, electrolytes, liver and kidney function tests, urinalysis||Recommended, in addition to TSH and hematocrit, by the American Geriatrics Society for depression in older adultsb|
aWomen diagnosed with premenstrual dysphoric disorder must have at least 5 of 11 symptoms: markedly depressed mood or hopelessness or self-deprecating thoughts; marked anxiety and tension; sudden sadness or increased sensitivity to rejection; persistent anger or irritability or increased interpersonal conflict; decreased interest in usual activities; difficulty concentrating; fatigue; change in appetite or overeating or having specific food cravings; hypersomnia or insomnia; feelings of being overwhelmed or out of control; physical symptoms (eg, breast tenderness, headaches).
Suicide Risk and Severity Assessment
Consider hospitalization under the care of a psychiatrist for patients who pose a serious threat of harm to themselves or others, are unable to care for themselves, have complicating psychiatric or general medical conditions, or have not responded adequately to outpatient treatment.25 The no-suicide contract (also called the contract for safety) for suicide prevention has not been well studied, is not enough to protect against legal liability, and should not replace thorough assessment of a patient’s suicide risk factors, consideration of hospitalization, referral, or close follow-up.28,29
Depression severity is determined based on the number of depressive symptoms present (in addition to the five required for an MDD diagnosis) along with the level of functional impairment. Severe depression is diagnosed when a patient displays most symptoms of depression and these markedly interfere with functioning, with or without psychotic symptoms.4,29 The PHQ-9 can be used to assess severity (total points + severity score) (available at http://www.depression-primarycare.org/clinicians/).
Before making an initial treatment decision, assess barriers to treatment adherence, discuss treatment expectations including the likely time course of symptom response, discuss the importance of treatment adherence for relapse prevention, and provide education.25
Treatment may include depression-focused psychotherapy, pharmacologic therapy (Table 5), both pharmacotherapy and psychotherapy, or other interventions based on depression severity, comorbid disorders, psychosocial stressors, and patient preference and prior treatment experiences.25
Table 5. Commonly Prescribed Antidepressants with Side Effect Profiles and Dosages
|Drug||Side Effects/Contraindications||Dosage (mg)|
|Selective serotonin reuptake inhibitors||Class effects: Agitation/insomnia, anxiety, dizziness/falls, extrapyramidal side effects, gastrointestinal effects, dry mouth, headache, sexual dysfunction, weight effects (small), serotonin syndromea, sweating; bleeding risk for elderly patients or those taking certain drugs (aspirin, nonsteroidal anti-inflammatory drugs, warfarin/anticoagulants)|
|Fluoxetine (Prozac)b,c||Somnolence; higher risk of discontinuation symptoms||20-80 daily|
|Paroxetine (Paxil)b,d||20-50 daily|
|Sertraline (Zoloft)b,c||Potential cardiac effects with doses greater than 40 mg||50-200 daily|
|Citalopram (Celexa)b,c||10-40e daily|
|Escitalopram (Lexapro)b,c||Potential cardiac effects with doses greater than 20 mg||10-20 daily|
|Serotonin-norepinephrine reuptake inhibitors||Class effects: Similar to those of SSRIs; dose-related hypertension; discontinuation syndrome may be protracted|
|Duloxetine (Cymbalta)c||Nausea (37%), xerostomia (22%)||40-60 daily|
|Venlafaxine (Effexor)b,c||75-375 daily divided into 2-3 doses|
|Desvenlafaxine (Pristiq)c||50-100 daily|
|Mirtazapine (Remeron)b,c||Somnolence (50%), weight gain, gastrointestinal effects, xerostomia||15-45 nightly|
|Bupropion (Wellbutrin)b,c Wellbutrin SRb||Agitation (32%), sweating (22%), edema, gastrointestinal effects, headache, nocturia, rash, seizure, tremor, ataxia/incoordination; contraindicated in patients with seizures||300-400 divided into 2 doses|
|Wellbutrin XLb||300-450 daily|
|Tricyclics||Class effectsf: Xerostomia, blurred vision, constipation, urinary retention. drowsiness, orthostatic hypotension/falls, dizziness, weight gain, myoclonus, confusion (in elderly patients); avoid use in patients with cardiac conduction abnormalities, benign prostatic hypertrophy, glaucoma|
|Amitriptyline (Elavil)b,c||50-150 nightly|
|Desipramine (Norpramin)b,c||100-200 daily|
aSerotonin syndrome (eg, changes in mental status, autonomic instability, neuromuscular abnormalities, gastrointestinal symptoms) may occur with concomitant use of SSRIs and SNRIs or SSRIs and triptans.
With respect to therapy type, there is strong evidence supporting the use of cognitive-behavioral therapy (CBT), interpersonal psychotherapy, and individual problem-solving therapy,25 with no differences shown between the first two therapies.32 There is some evidence supporting psychodynamic therapy, marital therapy, problem-solving therapy in group formats, and family therapy.31,33,34
Exercise improves depressive symptoms, but effects are modest and not statistically significant when considering only methodologically robust trials.35 Music therapy can improve mood,36 and relaxation reduces severity of self-reported depression compared with wait-list (delayed treatment) or no treatment, but not compared with CBT.37
The American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients with MDD 2010 update notes that effectiveness is similar among and within drug classes, so initial selection is primarily based on anticipated or tolerability of side effects, pharmacologic properties (eg, half-life, drug interactions), and factors such as prior drug response, cost, and patient preference.25 Other considerations include chronic pain or severe insomnia (consider a TCA or mirtazapine), comorbid medical conditions (avoid TCAs and citalopram [doses greater than 40 mg/day] in patients with cardiac conduction disturbances), successful response to prior antidepressant by the patient or first-degree relative (start with the same drug), and hypersomnia (consider SSRI). Use a lower initial dose if starting antidepressants in older individuals, in individuals with hepatic or renal dysfunction, or in pregnant women.25
In 2007, the Food and Drug Administration (FDA) issued a black box warning on all antidepressants (36 listed) approved for use in patients younger than 25 years to include increased risks of suicidality.40 The meta-analysis that raised this awareness did not show evidence of completed suicide in young patients taking SSRIs despite the increased risk of suicidality.36
Several aspects of drug treatment differ between women and men. Oral contraceptives may cause elevated serum levels of TCAs, as does the concomitant use of SSRIs and TCAs, so caution is advised. For perimenopausal women, SSRIs and SNRIs are useful in alleviating depression and reducing vasomotor symptoms; however, sexual dysfunction adverse effects occur frequently (35% to 70% of women on SSRIs).41 Another trial found that women responded more favorably to fluvoxamine (an SSRI) than men.42
Intravenous scopolamine has been shown to reduce symptoms in acute depression compared with placebo,43 with a greater response in women than men.44 Its role in treatment is unclear.
For pregnant woman with moderate to severe MDD, the APA recommends consideration of an antidepressant.25 Consider continuing medication for pregnant women who have MDD that is in remission, are on maintenance medication, and are deemed to be at high risk of a recurrence if the drug is discontinued.25 SSRIs are most commonly prescribed for pregnant women, but use in the third trimester has caused withdrawal symptoms in newborns (eg, jitteriness, increased muscle tone, irritability, altered sleep patterns, tremors, difficulty eating) and may be associated with preterm birth and low birth weight.45 Changes in pharmacokinetics during pregnancy may require dose adjustment. Most antidepressants have an FDA Pregnancy Category C classification (Table 5) due to limited research.
The Organization of Teratology Information Specialists (http://www.OTISpregnancy.org) provides information for patients about drug effects in pregnancy. Potential risks and benefits of antidepressant use during pregnancy or lactation should be discussed when considering use of these agents; the website http://www.womensmentalhealth.org contains information for patients considering this decision.
Breastfed infants should be monitored for persistent irritability and poor feeding. Information on drugs and breastfeeding can be found at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT.
One-third of patients with MDD experience a relapse within a year.2 To reduce the risk of relapse, patients successfully treated with drug therapy (PHQ-9 score of less than 5) should continue this therapy, generally at the same dosage, for 4 to 9 months.25 Depression-focused psychotherapy may also prevent relapse.25
S-Adenosylmethionine (SAMe) is possibly effective in mild to moderate depression, although most trials are methodologically flawed.48 SAMe may augment SSRIs for patients who do not respond to treatment.49 Tryptophan and 5-hydroxytryptophan appear to be more effective than placebo in alleviating depression but may be associated with potentially fatal eosinophilia-myalgia syndrome.50 There is insufficient evidence of benefit from acupuncture.51
Management of Side Effects
If at least a moderate improvement in symptoms is not observed within 4 to 8 weeks of treatment initiation, the diagnosis and treatment adherence should be reassessed and the treatment plan adjusted.25 For patients in psychotherapy, consider increasing the frequency of sessions and consult with the mental health professional about whether the selected treatment is meeting the patient’s needs. If drugs are prescribed, optimize the dose if tolerated or consider a different drug of any class other than a non-monoamine oxidase inhibitor (non-MAOI).25 Other options include augmenting the antidepressant with depression-focused psychotherapy or with another antidepressant agent; collaborative care with a mental health professional should also be considered.
When switching from one antidepressant to another, the drug half-life should be considered; most drugs can be switched within 1 week (ie, they have a 1-week washout period).25 When switching from fluoxetine or paroxetine to a TCA, start at a lower dose because these drugs inhibit the metabolism of TCAs. If switching to or from one SSRI to another, use caution to prevent serotonin syndrome.
Nonselective MAOIs (eg, phenelzine) are generally reserved for patients who do not respond to drug therapy, due to the needed dietary restrictions and many drug-drug interactions.25 Psychiatrists also augment antidepressants with drugs such as lithium or second-generation antipsychotics, or agents such as thyroid hormones. For patients whose symptoms have not responded adequately to drug therapy, ECT is the most effective form of therapy and should be considered.25
Maintenance Versus Discontinuation of Pharmacotherapy
If the decision is made to discontinue drug therapy, it is best to taper the drug dosage over several weeks to minimize withdrawal symptoms and symptom recurrence.25 After discontinuation, monitor patients closely for the next few months for recurrence, and educate the patient and family about symptoms of relapse.