The impact of major depressive disorder (MDD) on patients and their families is substantial. MDD adversely affects the patient as well as others, with the most serious complication of a major depressive episode being suicide. The disorder has also been associated with significant medical comorbidity. It can complicate recovery from other medical illnesses. Furthermore, MDD affects patients’ marital, parental, social, and vocational functioning. The disorder is unremitting in about 15% of patients and recurrent in another 35%. Compounding the problem is that treatment is often delayed. These factors highlight the need for changes in the delivery of mental health services to enhance timeliness and quality of care in MDD. With treatment, however, the prognosis associated with MDD is generally good. Most patients will respond to acute treatment, and continuation and maintenance therapy with acutely active treatments has been shown to lower the risk and severity of relapses into depression.

Revisiting Previous Guidelines

In 2010, the American Psychiatric Association (APA) released a new clinical practice guideline for the treatment of patients with MDD. This document (available online at, the third since guidelines were originally created by the APA for MDD, revises a previous version that was published about a decade ago. “It includes new evidence-based recommendations on the use of antidepressant medications, depression-focused psychotherapies, and somatic treatments, such as electroconvulsive therapy,” says Alan J. Gelenberg, MD, who chaired the workgroup that developed the recommendations. “The guideline also addresses other topics, such as alternative and complementary treatments, treating depression during pregnancy, and strategies for treatment-resistant depression.”

It took approximately 5 years to update the APA guidelines, Dr. Gelenberg says. “The update involved intense review, discussion, and thoughtful revision-making. We believe this update will enhance patient care, and we’re hopeful they’ll improve lives for many patients.” The workgroup consisted of APA members with extensive research and clinical expertise in the assessment and treatment of MDD. It reviewed over 13,000 articles that were published from 1999—when the search from the previous edition ended—to 2006. Draft versions of the guideline underwent extensive review by experts in psychiatry, allied physician organizations, patient advocacy groups, and members of the APA.

What’s New?

The 2010 guideline update includes new information on depression rating scales, strategies for treatment-resistant depression, recommendations on exercise and other healthy behaviors, and a strengthened recommendation on maintenance treatment. While this new information is a welcome addition, Dr. Gelenberg notes that formulating plans for enhancing medication adherence (Table 1) and for appropriate patient monitoring (Table 2) are still paramount to providing quality care. “It’s important that physicians make time to address the patient’s need for treatment and follow-up with them closely and frequently to optimize results,” he says.

“It’s important that physicians make time to address the patient’s need for treatment and follow-up with them closely and frequently to optimize results.

–Alan J. Gelenberg, MD

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With regard to rating scales, the APA guideline recommends using a clinician- and/or patient-administered rating scale to assess the type, frequency, and magnitude of psychiatric symptoms. This may enable healthcare providers to tailor treatment plans to match the needs of each patient. The guideline also discusses approaches to managing treatment-resistant depression. Electroconvulsive therapy has the strongest data to support it as a treatment for patients who do not respond to multiple medication trials. Transcranial magnetic stimulation and vagus nerve stimulation have also been added as potential treatments for these patients. Monoamine oxidase inhibitors are another option.

The APA guideline also cites randomized, controlled trials that demonstrate at least a modest improvement in mood symptoms for patients who engage in aerobic exercise or resistance training. “Regular exercise may reduce the prevalence of depressive symptoms in the general population,” Dr. Gelenberg says. “Specific benefits have been found in older adults and in those with co-occurring medical problems.” In addition, the guideline recommends that maintenance treatment be considered after continuation treatment phases, especially for those with risk factors for MDD recurrence. Maintenance treatment should be provided for patients with three or more prior depressive episodes or chronic or severe illness.

Looking Ahead

Although notable progress has been made in the understanding of MDD and its treatment, there are still many unanswered questions on the optimization and individualization of treatment. “To better personalize care, clinicians need a better understanding of what causes depression,” says Dr. Gelenberg. “Also, while the science of psychotherapy research continues to evolve, researchers are striving to understand how specific types of therapy compare with each other and how to select the most appropriate individualized treatments. Furthermore, it would be helpful to accumulate more comparative data on efficacy, short- and long-term side effect profiles, and specific clinical indications of different antidepressants, augmentation strategies, and combination treatment approaches. In the meantime, clinicians should utilize the updated APA guideline as they use existing and novel treatment strategies for MDD.”



American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder, third edition. Available at:

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