Major depressive disorder (MDD) affects 16% of adults in the United States at some point in their lives. It is one of the most important causes of disability, time off from work, and personal distress, accounting for more than 8 million office visits per year.

Recent information shows that while 8% of the population screens positive for depression, only a quarter of those with depression receive treatment. Most patients with depression are cared for by primary care physicians, not psychiatrists.1 It is important that primary care physicians are familiar with the range of evidence-based treatments for depression and their relative efficacy. Most patients with depression receive antidepressant medication and less than one-third of patients receive some form of psychotherapy.1 The American College of Physicians guideline reviews the evidence regarding the relative efficacy and safety of second-generation antidepressants and nonpharmacologic treatment of depression.2

MDD is defined as depressed mood or loss of pleasure or interest along with other new onset symptoms, including significant change in weight or appetite, insomnia or hypersomnia, psychomotor agitation or retardation nearly every day, fatigue or loss of energy, feelings of worthlessness or excessive or inappropriate guilt, indecisiveness or decreased ability to concentrate, and recurrent thoughts of death or suicide, which last for at least 2 weeks and affect normal functioning. Three phases are identified in the treatment of depression: acute (6-12 weeks), continuation (4-9 months), and maintenance (1 year or more). Multiple approaches are used in treatment including psychotherapy, complementary and alternative medicine (CAM), exercise, and pharmacotherapy. Response to depression is defined as a 50% or greater decrease in the severity of symptoms. It is important to understand that many patients do not achieve a complete remission and therefore require either a change in therapy or augmentation of their current therapy with an additional intervention.

Outcomes evaluated in this guideline include response, remission, functional capacity, quality of life, reduction of suicidality or hospitalizations, and harms.

The pharmacotherapy treatment of depression, as assessed in this guideline, are second-generation antidepressants (SGAs), which include selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and selective serotonin norepinephrine reuptake inhibitors. Previous reviews have shown that the SGAs have similar efficacy and safety with the side effects varying among the different medications; common side effects include constipation, diarrhea, nausea, decreased sexual ability, dizziness, headache, insomnia, and fatigue.

The strongest evidence, rated as moderate quality, comes from trials comparing SGAs to a form of psychotherapy called cognitive-behavioral therapy (CBT). CBT uses the technique of “collaborative empiricism” to question patients maladaptive beliefs, and by examining those beliefs, help patients to take on interpretations of reality that are less biased by their initial negative thoughts. Through these “cognitive” exercises, patients begin to take on healthier, more-adaptive approaches to the social, physical, and emotional challenges in their lives. These interpretations are then “tested” in the real world, the behavioral aspect of CBT. Studies that ranged in time from 8 to 52 weeks in patients with MDD showed SGAs and CBT to have equal efficacy with regard to response and remission of depression to therapy. Combining SGA and CBT, compared with SGA alone, did not show a difference in outcomes of response to therapy or remission of depression, though patients who received both therapies had some improved efficacy in work function.

When SGAs were compared with interpersonal therapy, psychodynamic therapy, St. John’s wort, acupuncture, and exercise, there was low-quality evidence that these interventions performed with equal efficacy to SGAs. Two trials of exercise, compared with sertraline, had moderate-quality evidence showing similar efficacy between the two treatments.

When patients have an incomplete response to initial treatment with an SGA, there was no difference in response or remission when using a strategy of switching from one SGA to another versus switching to cognitive therapy. Similarly, with regard to augmentation, CBT appears to work equally to augmenting initial SGA therapy with bupropion or buspirone.

The guidelines discuss that, with regard to adverse effects, while the discontinuation rates of SGAs and CBT are similar, CBT likely has fewer side effects. In addition, it is important to recognize that CBT has lower relapse rate associated with its use than do SGAs. This is presumably because once a skill set is developed when learning CBT, those skills can continue to be used long term.

The bottom line

Most patients who experience depression are cared for by their primary care physician. Treatments for depression include psychotherapy, complementary and alternative medicine (CAM), exercise, and pharmacotherapy. After discussion with the patient, the American College of Physicians recommends choosing either cognitive-behavioral therapy or second-generation antidepressants when treating depression.


1. Olfson M, Blanco C, Marcus SC. Treatment of Adult Depression in the United States. JAMA Intern Med. 2016 Oct;176(10):1482-91 .

2. Qaseem A, et al. Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016 Mar 1;164:350-59 .

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University in Philadelphia. Aaron Sutton is a behavioral therapy consultant in the family medicine residency program at Abington Memorial Hospital.