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There is a growing body of evidence that supports the use of atypical antipsychotics as augmentation agents for nonpsychotic unipolar major depressive disorder (MDD) in adults. Unfortunately, varying definitions of treatment-resistant depression, the limited evidence available for interventions after two or more treatment failures, and when and whether to use medications from nonantidepressant classes, remain a key gap in the knowledge base for clinicians. We identified and reviewed the following guidelines to discuss the status of augmentation therapy with atypical antipsychotic agents in MDD: American Psychiatric Association practice guidelines for treatment of patients with MDD; Canadian Network for Mood and Anxiety Treatments clinical guidelines for the management of MDD in adults; National Institute for Health and Clinical Excellence guidelines for treatment and management of depression in adults; British Association of Psychopharmacology guidelines for treatment of depressive disorders; Institute for Clinical Systems Improvement healthcare guideline for MDD in adults in primary care; clinical practice recommendations for depression; international consensus statement on MDD; German Society of Psychiatry, Psychotherapy and Neurology guidelines for unipolar depression; and World Federation of Societies of Biological Psychiatry guidelines for biological treatment of unipolar depressive disorders in primary care. Reflecting the cumulative evidence in the past decade, augmentation strategies including atypical antipsychotic augmentation are recommended in most guidelines for partial or nonresponders, at the same stage as switching or combination strategies. However, there are few direct comparisons of different augmentation strategies and little information about the optimal duration of augmentation strategies or use in special populations. Clinicians should note that guidelines are derived from an evolving database of evidence and cannot take into account the myriad of clinical variables that differ between individual patients. Therefore, they are intended to provide a useful framework for the management of depression and should be used in conjunction with other recognized sources of patient information and the application of clinical wisdom.

Atypical Antipsychotic Augmentation Strategies in the Context of Guideline-based Care for the Treatment of Major Depressive Disorder