Doctors should select cognitive behavioral therapy (CBT) or second generation antidepressants (SGAs) to treat adults with major depressive disorder (MDD), the American College of Physicians (ACP) recommends in a new evidence-based clinical practice guideline published today in Annals of Internal Medicine.

“Patients are frequently treated for depression by primary care physicians, who often initially prescribe SGAs,” said ACP President Wayne J. Riley, MD, MPH, MBA, MACP. “However, CBT is a reasonable approach for initial treatment and should be strongly considered as an alternative treatment to SGAs where available, and after discussing treatment effects, adverse effect profiles, costs, accessibility, and preferences with patients.”

Depression is a medical condition causing sadness that interferes with daily life, not a normal reaction to life situations such as the death of a loved one or the loss of a job. Common depression symptoms are lack of energy and loss of interest in things previously enjoyed.

ACP developed the guideline to summarize and grade the evidence on the comparative effectiveness and safety of non-drug treatments and SGAs (including SSRIs, SNRIs, bupropion, mirtazapine, nefazodone, and trazodone), alone or in combination, for MDD in adults. Evaluated outcomes included response, remission, functional capacity, quality of life, reduction of suicidality or hospitalizations, and harms.

Moderate-quality evidence showed that CBT and SGAs are similarly effective treatments for MDD and that discontinuation rates are similar for CBT and SGAs. Low-quality evidence showed no difference in effectiveness or adverse effects between first line treatment using SGAs compared to non-drug treatments (complementary and alternative medicines, or exercise monotherapies or combination therapies).

Adverse effects commonly associated with SGAs include constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual adverse events, and drowsiness.

For second line treatment after treatment failure with SGAs, low-quality evidence showed that strategies to switch to or augment with another drug or non-drug therapy are similarly effective.

Low-quality evidence showed that St John’s wort may be as effective as SGAs for treating MDD, and moderate-quality evidence showed that St John’s wort was better tolerated than SGAs. However, St. John’s wort is not currently regulated by the Food and Drug Administration in the U.S. Because no standard is in place regarding the contents and potency of the medication, patients in the U.S. may not be able to get quality-controlled St John’s wort or reliably obtain preparations with similar effectiveness as those used in the included studies.

Adverse effects associated with St. John’s wort may include mild gastrointestinal symptoms, skin reactions, fatigue, sedation, restlessness, dizziness, headache, and dry mouth. St. John’s wort is associated with important drug-drug interactions, is known to induce CYP3A4, may reduce the bioavailability or efficacy of some drugs, and is contraindicated in patients taking monoamine oxidase inhibitors or SSRIs.