Among patients with depression, the presence of many aspects of illness which may be associated with bipolar disorder does not appear to be associated with treatment resistance—evidence against the common hypothesis that some cases of difficult-to-treat depression are actually unrecognized bipolar disorder, according to a report posted online today that will appear in the April 2011 print issue of Archives of General Psychiatry, one of the JAMA/Archives journals. However, many patients with depression also report psychotic-like symptoms, such as hearing voices or believing they are being spied on or plotted against, and those who do are less likely to respond to treatment.
"The distinction between major depressive disorder and bipolar disorder remains a challenging clinical problem when individuals present with a major depressive episode," the authors write as background information in the article. "The identification of individuals at risk for bipolar disorder is of more than academic importance, as treatment may be markedly different; in particular, antidepressants have been suggested to exacerbate the illness course of at least a subset of bipolar individuals."
To assess the association between features of bipolar disorder and the outcomes of treatment for depression, Roy H. Perlis, M.D., M.Sc., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues studied 4,041 adults with a diagnosis of depression. Patients were treated with the antidepressant citalopram, followed by up to three next-step treatments as needed depending on their response.
At the beginning of the study, patients were asked about psychotic symptoms—including beliefs about being controlled, having special powers or being plotted against. Almost one-third (1,198, or 30 percent) of the patients reported having at least one such symptom in the previous six months. Those who did were significantly less likely to go into remission over all the treatment periods
Participants were also asked about other features characteristic of bipolar disorder; 1,524 patients (38.1 percent) with depression described at least one manic-like symptom. One of these, irritability, was also associated with poor treatment outcomes. "On the other hand, several indicators consistently associated with bipolar disposition in the literature, including history of manic symptoms and family history of bipolar disorder, were not associated with outcome of treatment with antidepressants in the STAR*D study," the authors write. "Briefer episode duration, suggested to represent a risk marker for bipolarity, was associated with greater likelihood of remission."
"Considered as a whole, our results cast doubt on the frequent assertion that unrecognized bipolar disorder is widespread in clinical practice and particularly in treatment-resistant major depressive disorder," they conclude. "Screening for bipolar disorder among psychiatric patients remains important, as does considering individual risk factors such as family history or age at onset. Still, our findings indicate that, in most individuals presenting with a major depressive episode without a prior manic or hypomanic episode, unrecognized bipolarity does not appear to be a major determinant of treatment resistance."
(Arch Gen Psychiatry. Published online December 6, 2010. doi:10.1001/archgenpsychiatry.2010.179. Available pre-embargo to the media at www.jamamedia.org.)
Editor's Note: The STAR*D study is supported by National Institutes of Mental Health grants. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
To contact Roy H. Perlis, M.D., M.Sc., call Sue McGreevey at 617-724-2764 or e-mail smcgreevey@partners.org.
For more information, contact JAMA/Archives Media Relations at 312/464-JAMA (5262) or e-mail mediarelations@jama-archives.org.