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Am J Psychiatry. 2006 Jul;163(7):1219-25.

What happened to lithium? Antidepressant augmentation in clinical settings.

Author information

Health Services Research and Development, VA Medical Center, P.O. Box 130170, Ann Arbor, MI 48113-0170, USA.

Erratum in

  • Am J Psychiatry. 2006 Sep;163(9):1648-9.



Antidepressant augmentation is recommended when patients do not respond to antidepressant monotherapy. However, little is know about antidepressant augmentation in clinical settings and whether these practices reflect the research evidence.


The authors identified 244,859 patients in Veterans Administration mental health settings with a diagnosis of depression and an antidepressant prescription during fiscal year 2002. Patients with schizophrenia, dementia, or bipolar I disorder were excluded. The authors examined the prevalence and characteristics of antidepressant augmentation during the year, defined as receiving an antidepressant and an augmenting agent (lithium, second-generation antipsychotics, combinations of antidepressants, anticonvulsants, or "other") for >/=60 consecutive days in specified doses for those without other clinical indications. Mixed-effect models were used to examine predictors of augmentation.


Some patients (22%) received an augmenting agent. The most commonly used agents were a second antidepressant (11%) and a second-generation antipsychotic (7%). Only 0.5% of the patients received lithium. Whites, younger patients, and those with a prior hospitalization were more likely to receive augmentation. African Americans were more likely to receive antipsychotic augmentation; whites were more likely to receive lithium.


Antidepressant augmentation is common in clinical settings. Although lithium currently has the most research support, antipsychotic medications and a second antidepressant are the most widely used augmenting agents. Many augmenting agents are used across clinical and demographic groups. Research is needed on the relative effectiveness of these agents, along with efforts to promote the use of agents with the greatest level of research support.

[Indexed for MEDLINE]

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