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Atypical Antipsychotic Augmentation in the Treatment of Depression

Atypical Antipsychotic Augmentation in the Treatment of Depression

Despite the clinician's goal of treating the depressed patient to the point of remission, this state is generally achieved in only 15% to 30% of patients.1 Another 10% to 30% of patients respond poorly to antidepressant treatment, while 30% to 40% have a remitting and relapsing course.1 Patients without a major depressive disorder are likely to be treated successfully by primary care physicians and/or other mental health professionals, which leaves psychiatrists to treat patients who have forms of depression that are less responsive to treatment.

Initially, patients may have high expectations of treatment outcome, only to discover that many forms of depression are not readily responsive to even adequate dosages of an antidepressant. Such patients have been described as having difficult-to-treat depression.2 Other patients with treatment-resistant forms of depression are defined as having depressions that do not respond to various numbers of treatment trials.3

As psychiatrists, how do we help patients who continue to experience significant depressive symptoms, despite the use of evidence-based first-line treatment? Options that are currently available for the treatment of depressive disorders include monotherapy with an antidepressant medication; psychosocial treatment (individual, family, or group therapy); combined pharmacotherapy and psychosocial treatment; substitution of one antidepressant for another; augmentation of an antidepressant with other agents such as lithium, thyroid hormone, or atypical antipsychotic agents; a combination of antidepressants; electroconvulsive therapy; repetitive transcranial magnetic stimulation; and vagus nerve stimulation.

One of the most common options that clinicians recommend is augmentation. In a large-scale study (N = 244,859), 22% of patients with depression were found to have received an augmenting agent; a second antidepressant (11%) or a second-generation antipsychotic (7%) were the most common agents added to treatment.4

Most literature on treatment-resistant or difficult-to-treat depression presents findings from clinical trials of various agents that typically have a small number of patients, are open-label studies, and lack control subjects. DeBattista5 noted, "The most common augmentation strategies in depression are those with the least controlled evidence."

Mental health professionals seem as ready as patients to seek easy solutions to difficult problems. Although a variety of alternative pharmacological treatment trials have yielded benefits for some patients, the STAR*D studies have highlighted the limitations of such sequential trials. Sequential and augmentation trials have yielded 15% to 30% remission rates.6,7

Given this evidence, it is important for patients to have realistic expectations about the nature of their depressive illness and for clinicians to help them find ways to cope with depression, even while they continue to test responsiveness to new treatments. Excessively focusing on symptom resolution may paradoxically worsen a patient's psychosocial functioning and quality of life. Disease management approaches that focus on learning how to deal with one's illness in the face of symptom persistence have been used successfully with a number of medical conditions, including chronic fatigue syndrome, diabetes, arthritis, chronic pain, and asthma.1 Evidence-based treatment can be best pursued within the context of a broadly based model for coping with chronic illness.

What evidence exists for the efficacy of atypical antipsychotic augmentation? When is atypical antipsychotic augmentation appropriate, and which agents should be used and for how long? Possible answers to these questions are addressed below.


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