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Am Fam Physician. 2023;107(3):323-325

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Key Points for Practice

• In uncomplicated major depression, combining medications and psychotherapy is not more effective than monotherapy.

• For severe, persistent, or recurrent major depression, combining medications and psychotherapy is more effective than monotherapy.

• Continuing medications for at least six months after symptom remission will reduce relapse by nearly one-third.

• When patients with symptom remission are at high risk of relapse, cognitive behavior therapy, interpersonal therapy, or mindfulness-based cognitive therapy can reduce relapse risk.

From the AFP Editors

One in five people in the United States is diagnosed with major depression during their lifetime, and one in 10 copes with depression in any given year. Women have twice the risk of depression as men. Risk is higher in younger adults, people with lower incomes, and White and Native American ethnicities. The U.S. Department of Veterans Affairs and U.S. Department of Defense (VA/DoD) published guidelines on the management of major depressive disorder.

Screening for Depression

The U.S. Preventive Services Task Force recommends screening all patients for depression. The two-question Patient Health Questionnaire (PHQ-2) can be used, and if positive the longer PHQ-9 can be used for follow-up. These questionnaires are recommended for older adults because of similar sensitivity to geriatric-specific screening tools. Although the Edinburgh Postnatal Depression Scale is commonly used for pregnant and postpartum patients, the PHQ-2 is also effective for this population.


Although screening tools can suggest major depression, diagnosis requires five or more symptoms from the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. to present within the same two-week period, with one being either depressed mood or loss of interest or pleasure in almost all activities. Symptoms must cause significant distress or functional impairment. Substance misuse or a medical condition that could cause similar symptoms should be ruled out. The diagnostic evaluation is an opportunity to ask about treatment history and suicide attempts as well as current suicidal or homicidal ideation.

Treatment Setting

Collaborative care models, which include multiprofessional care, structured management, scheduled follow-up, and interprofessional communication, improve patient symptoms and satisfaction over usual care. Psychiatrist availability to recommend treatment further improves outcomes. Although collaborative care is effective in primary care settings, team-based care does not improve outcomes in specialty environments.

Interventions delivered by telehealth appear to be as effective as in-person treatment. Limited study shows similar improvements in depressive symptoms and quality of life.

Treatment of Uncomplicated Major Depression

People diagnosed with uncomplicated major depression (i.e., PHQ-9 score of 20 or less) are most often best treated with either psychotherapy or pharmacotherapy alone, although other treatments may be effective as well. Combining therapy and medication is not helpful unless depression is severe, persistent, or recurrent.


Several types of psychotherapy are effective for depression (Table 1), and all appear to have similar effectiveness. Group and individual psychotherapy improves depressive symptoms compared with the waiting list or usual care options and appear similarly effective. Guided internet-based cognitive behavior therapy appears to be beneficial for mild to moderate depression based on low-quality evidence. If patients decline medications and psychotherapy, another option is nondirective supportive therapy, which slightly improves depressive symptoms based on low-quality evidence.

Type of therapyDescription
Acceptance and commitment therapyIdentifying personal values and actionable goals based on those values
Behavioral therapyMonitoring and identifying relationships between symptoms and behaviors and attempting to increase rewarding activities
Cognitive behavior therapyInterventions are aimed at helping the patient to modify their behavior and thinking
Interpersonal therapyImprove interpersonal functioning by focusing on role conflict, interpersonal loss, role change, and interpersonal skills
Mindfulness-based cognitive therapyMindfulness-based interventions combined with cognitive behavior therapy (e.g., mindfulness meditation)
Problem-solving therapyShort-term approach of skills acquisition to work on specific problem areas
Short-term psychodynamic psychotherapyFocusing on and learning from unconscious conflicts to change future behavior


When choosing a medication, bupropion, mirtazapine, serotonin-norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and trazodone are similarly effective. Monoamine oxidase inhibitors, nefazodone, and tricyclic antidepressants are effective, but their low therapeutic indices and significant risk of toxicity limit use. Evidence for ketamine and esketamine (Spravato) is limited to patients with persistent depression.

Use of pharmacogenetic testing to guide medication choice does not appear to improve treatment outcomes.

For patients with uncomplicated major depression who are not pregnant or breastfeeding and prefer herbal therapy, St. John’s wort, which reduces symptoms more than placebo and is comparable to antidepressant medications, is an option. Adverse effects are less common than with standard antidepressants and include gastrointestinal upset, mild sedation, restlessness, photosensitivity, and serotonin syndrome. As a cytochrome P450 3A4 enzyme inducer, St. John’s wort can reduce the effectiveness of some medications, including oral contraceptives. Dosing is three times daily, starting at 300 mg per dose. Because St. John’s wort is an herbal medication, dosing may not be consistent among formulations.

Other Treatments

All patients with uncomplicated major depression may benefit from adjunctive therapies, including exercise, bibliotherapy, and light therapy. Exercise improves symptoms in major depression compared with the waiting list or usual care options, although evidence is very low quality. Bibliotherapy, or reading literature as psychological support, is more effective than usual care. Light therapy improves symptoms whether they follow a seasonal pattern or not. Biofeedback and meditation may have slight benefit as adjunctive therapies, although evidence is very low quality.

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Coverage of guidelines from other organizations does not imply endorsement by AFP or the AAFP.

This series is coordinated by Michael J. Arnold, MD, contributing editor.

A collection of Practice Guidelines published in AFP is available at

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