The American Psychiatric Association has issued a third edition of its Practice Guideline for the Treatment of Patients With Major Depressive Disorder, the first full revision in 10 years.

While changes from the previous version are not radical, the new document reflects a significant evolution in approaches to this highly prevalent condition, including additions to the pharmacotherapy arsenal and a wider selection of nondrug treatments.

Most fundamental, perhaps, is “an emphasis on the quality of care,” says Michael E. Thase, MD, professor of psychiatry at the University of Pennsylvania in Philadelphia and member of the work group that wrote the guideline.

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The revision pays particular attention to how patients are treated — frequency of follow-up and monitoring of symptoms, side effects, and adherence — as well as to what treatments are used. This strategy reflects research that finds modest differences between interventions and shows that “nonspecific aspects of care are at least as important as specific ones,” notes Dr. Thase.

Safety first

The guideline stresses the need to evaluate the patient’s capacity for self-care and risk of self-harm at the outset of therapy and periodically thereafter, with hospitalization considered for those who pose a danger to themselves or others.

Before initiating treatment, assess the patient’s medical condition with a full examination and history. “Depression can complicate chronic medical illness, and chronic illness is a risk factor for depression and predicts a poor outcome,” explains Dr. Thase.

Based on availability and resources, patients with mild-to-moderate depression should be offered the choice of appropriate psychotherapy or pharmacotherapy. When depression is severe, medication is generally indicated.


For most patients, the guideline states, the first drug tried should be a selective serotonin reuptake inhibitor (SSRI), a serotonin norepinephrine reuptake inhibitor (SNRI), or the antidepressants bupropion (Aplenzin, Wellbutrin) or mirtazapine (Remeron). The list of first-line drugs includes two that have been added since 2000: the SSRI escitalopram (Lexapro) and the SNRI duloxetine (Cymbalta).

These agents are all roughly equivalent in effectiveness. When choosing, take into account patient preference and prior experience, side-effect profile, concurrent medication, and comorbid conditions.

“I encourage primary-care practitioners [PCPs] to know two or three antidepressants really well and to be confident in their use,” Dr. Thase says.

Whatever the drug, increasing dosage gradually from a low level generally will minimize side effects. Although some patients may respond more quickly, clinicians should allow four to six weeks at the full dose to judge whether an antidepressant is working and another six weeks to achieve full effect.


Close follow-up is particularly important at the start of treatment. “Within the constraints of the practice, I’d encourage PCPs to include a telephone check-in within a week, and if feasible, a follow-up visit within two weeks,” advises Dr. Thase.

Clinicians should routinely alert patients to the possibility that symptoms will get worse rather than better in the first days or weeks of therapy, and should provide after-hours contact information.

Follow-up visits throughout the course of treatment should be used to monitor symptoms, side effects of drugs, and adherence. The new guideline strongly endorses the use of patient rating scales to assess response to treatment. Dr. Thase notes that the Patient Health Questionnaire-9 (PHQ-9) was designed for primary care and is particularly serviceable in this setting. “The patient can fill it out within five to seven minutes in the waiting room.” (Forms are available from the MacArthur Initiative on Depression and Primary Care)