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.

Approximately 10% of U.S. adults have a mood disorder, with 45% having a disorder classified as severe.⁴ Women as compared with men are 50% more likely to experience a mood disorder during their lifetime,¹ and 70% more likely to have depression.⁵

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

Depression is likely caused by a combination of genetic, biologic, environmental, and psychological factors. Evidence supporting a hormonal influence includes the increased incidence of depression at puberty, postpartum, menopause (for at-risk women), and the link between depressive symptoms and the menstrual cycle luteal phase.^10,11 Risk factors for women during pregnancy, the postpartum period, and at midlife are shown in Table 2.^12-17 In pregnant women, the greatest risk factor is MDD in a prior pregnancy; 25% to 50% of women with such a history have a recurrence in a subsequent pregnancy.¹⁴

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

The U.S. Preventive Services Task Force recommends depression screening in adults only when staff-assisted supports for depression care (ie, clinical staff providing direct depression care such as care coordination, case management, or mental health treatment) are in place to ensure accurate diagnosis, effective treatment, and follow-up.¹⁹ The optimal screening interval is unknown. The American Congress of Obstetricians and Gynecologists recommends that screening for antepartum and postpartum depression be strongly considered despite lack of evidence for benefit of universal screening.^7,20,21 Another approach is to conduct periodic risk-based screening in patients with MDD risk factors (Table 2).

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.

The current diagnostic criteria for depression, based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) is available online from the American Psychiatric Association.⁴ The DSM-5, which is due to be published in May 2013, will include a suicide risk assessment as well as a revised Depressive Disorder Not Elsewhere Classified category for diagnosing individuals who do not meet the criteria for a mood disorder but have depressive symptoms severe enough to cause dysfunction.^23,24 The DSM-5 Work Group is also proposing new severity ratings, one of which is the PHQ-9 score.

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

When a diagnosis of depression is suspected or confirmed, assess suicide risk. A positive response to the question “Have you had thoughts about killing yourself?” should prompt additional queries into plans, intent, means, previous attempts, and suicide among family members or friends.²⁵ Women are more likely to attempt suicide than men; women’s risk factors for suicide completion are shown in Table 2.^1,27

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/).

Initial treatment goals are inducing MDD remission and achieving a return to the patient’s baseline function level.²⁵ Collaborative care models involving case managers to link primary care providers, patients, and mental health subspecialists produce the best care for patients with MDD.³⁰

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

Depression-focused psychotherapy alone can be used as initial treatment in patients with mild to moderate MDD, especially in the presence of significant psychosocial stressors or interpersonal difficulties. Nonpharmacologic therapy is also suggested as initial treatment for pregnant or lactating women, unless symptoms are severe.²⁵ A Cochrane Review, however, found insufficient evidence supporting psychological support or psychotherapy alone for antepartum depression.³¹

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

Antidepressants (Table 5) can also be used as initial therapy for patients with mild to moderate MDD and should be used for those with severe MDD unless electroconvulsive therapy (ECT) is planned.²⁵ Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are effective and available in generic formulations. Other drugs considered to be optimal for most patients include serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine, or bupropion (Table 5).²⁵ The number needed to treat for SSRIs ranges from 7 to 8, and for TCAs from 7 to 16.³⁸ The number needed to harm (mainly due to withdrawal from side effects) ranges from 20 to 90 for SSRIs, and from 4 to 30 for TCAs. Fluoxetine is effective in reducing depression symptoms in children and adolescents.³⁹ SSRIs are also used for postpartum depression, although other drugs have been found to be equally effective.¹⁴

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

St. John’s wort (Hypericum perforatum) is widely used by individuals with depressive symptoms. A Cochrane Review found St. John’s wort to be more effective than placebo for MDD and to be comparable with standard antidepressants with fewer side effects.⁴⁶ Because this supplement is available as an over-the-counter product, physicians may be unaware of its use by patients. Supplement-drug interactions can occur, including with warfarin (reduced effectiveness), oral contraceptive pills (reduced effectiveness, break-through bleeding), and SSRIs (serotonin excess).⁴⁷

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

Electroconvulsive therapy may be considered for depression management in patients who have severe symptoms, do not respond to drug therapy, or prefer ECT. Additionally, ECT can be undertaken during pregnancy in women with psychotic or catatonic features.²⁵

Monitor treatment response, side effects, and patient safety/suicidality at a frequency based on symptom severity (including suicidal ideation), comorbid disorders, treatment adherence, and social support.²⁵ In general, patients who are not considered at increased suicide risk should be seen every two weeks after starting antidepressants. Patients at increased suicide risk or who are younger than 30 years should be seen at least weekly for three months after starting antidepressants.²⁵ While no treatment should continue unmodified in the absence of symptomatic improvement after one month (ie, decrease of greater than 4 points in PHQ-9 score), both psychotherapy and pharmacological therapy can take 8 to 14 weeks before the patient experiences the full effects.

If antidepressant side effects occur, an initial strategy is to lower the dose or change to an antidepressant that is not associated with the side effects being experienced.²⁵ Strategies to address sexual side effects include changing to another SSRI or adding bupropion or sildenafil; most interventions fail to show significant benefit on sexual function.⁴¹

Many patients will not respond to initial depression treatment. Results from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, which was performed in psychiatric and primary care clinics, found that only approximately 30% of patients experienced remission after 12 to 14 weeks on citalopram.⁵² For those who did not experience remission, an additional 30% of patients eventually achieved remission regardless of treatment change (eg, switching to a new antidepressant, adding a medication, switching to or adding CBT).

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

Patients who have had three or more MDD episodes or who have chronic MDD should continue on maintenance therapy indefinitely and at the same therapeutic dosage.²⁵ Psychotherapy with reduced session frequency is an option. For patients with fewer MDD episodes, consider maintenance therapy for those with other recurrence risk factors (eg, residual symptoms, ongoing psychosocial stressors, onset before age 20 years, second episode within 1 year of the first, family history of mood disorders).²⁵
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.

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