Adherence to treatment may be particularly problematic in light of the pessimism and demoralization intrinsic to depression and the delayed onset of antidepressants benefits. Involving the patient and family in treatment decisions, counseling them about what to expect, addressing misconceptions about the disease and its treatment, and encouraging full discussion of side effects and concerns may help promote adherence, according to the guideline.


Although most PCPs are not trained to administer psychotherapy, patients should be made aware of the options available, particularly if a preference for this kind of treatment is expressed. Since the issuance of the earlier edition of the guideline, research evidence has validated a broader variety of depression-focused therapies, which now include cognitive-behavioral therapy, interpersonal therapy, psychodynamic therapy, and problem-solving therapy. These modalities have been found effective in both individual and group settings.

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The authors suggest that psychotherapy might be particularly suitable for patients under significant psychosocial stress and for those with interpersonal difficulties. Psychotherapy should be considered a first-line treatment for women with mild-to-moderate symptoms who are or wish to become pregnant, or who are breastfeeding.

Combining medication and psychotherapy may be worthwhile when a patient’s depressive symptoms are moderate or worse and in milder cases that are complicated by psychosocial problems.

Inadequate response

When patients do not respond adequately to a full trial of an antidepressant, options include switching to a different antidepressant and adding psychotherapy or a second drug.

Agents to be considered for augmentation now include the second-generation antipsychotics (SGAs) olanzapine (Zyprexa), aripiprazole (Abilify), and quetiapine (Seroquel). Given the possibility of adverse effects that may include significant weight gain and metabolic disregulation, reserve these drugs for cases in which remaining symptoms are substantial. Typically, the guideline suggests, SGA augmentation is considered after poor response to two or more antidepressants.

Transcranial magnetic stimulation, another recently added alternative, has been shown effective in patients who have failed a single course of antidepressants. The treatment, which involves the application of a powerful magnetic field to the head, is quite benign and may be a good choice for individuals who are very sensitive to medication side effects. However, availability and convenience are likely to be limiting factors.

Referral and consultation

Although PCPs can care for most patients with uncomplicated depression, referral should be considered when the breadth of symptoms or safety issues so warrant, or when clinicians have used the drugs with which they feel comfortable without success.

“I would recommend getting a psychiatrist involved when there are suggestions of bipolar illness—when the patient gets worse instead of better with an antidepressant, for example,” affirms Dr. Thase.

Such symptoms as irritability, restlessness, or agitation; racing thoughts; dramatic upward shift in mood; or increased libido may be particular cause for concern.

Duration of treatment

Major depression is a chronic disease. Successful pharmacotherapy should continue for at least four to nine months at the same dose after remission of symptoms. When the risk of recurrence is high (for example, if the patient has had three or more prior depressive episodes), consider indefinite maintenance treatment.

See the patient at intervals throughout continuation and maintenance treatment, and counsel him or her to be on the alert for signs that depression is returning.

Mr. Sherman is a freelance medical writer in New York City.


1. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. Available online. Accessed June 15, 2011.