Bipolar Disorder Underlying Major Depression May Be Missed

Laurie Barclay, MD

August 08, 2011

August 8, 2011 (UPDATED August 17, 2011) — The diagnosis of bipolar disorder may be missed in patients presenting with a major depressive episode, according to the results of a cross-sectional diagnostic study reported in the August issue of the Archives of General Psychiatry.

"Major depressive disorder, the most common psychiatric illness, is often chronic and a major cause of disability," write Jules Angst, MD, from the Division of Psychiatric Research, Zürich University Psychiatric Hospital in Zürich, Switzerland, and colleagues from the Bipolar Disorders: Improving Diagnosis, Guidance and Education (BRIDGE) Study Group. "Many patients with major depressive episodes who have an underlying but unrecognized bipolar disorder receive pharmacologic treatment with ineffective regimens that do not include mood stabilizers."

The goal of this study from the multicenter, multinational, transcultural BRIDGE initiative was to assess the frequency of bipolar disorder symptoms in patients presenting for treatment of major depressive episodes.

"This study shows that if we loosen the definition of bipolar disorder to include increased activity as a key specifier of hypomania and reduce the time requirement that increases confidence in a hypomania diagnosis, we make more 'bipolar' diagnoses in patients with major depression," Guy M. Goodwin, FRCPsych, FMedSci, W. A. Handley Professor of Psychiatry at the University of Oxford, United Kingdom, told Medscape Medical News when he was asked to provide an independent comment. "This is not surprising (indeed it has to happen), and Dr. Angst has shown it before."

The investigators identified 5635 adults seen at community and hospital psychiatry departments for an ongoing major depressive episode. Criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and previously described bipolarity specifier criteria were used to examine the prevalence of bipolar disorder. Logistic regression allowed determination of variables associated with bipolarity, with significant associations defined as an odds ratio greater than 2 and P < .001.

DSM-IV-TR criteria for bipolar disorder were met by 903 patients (16.0%; 95% confidence interval [CI], 15.1% - 17.0%), and bipolarity specifier criteria were met by 2647 patients (47.0%; 95% CI, 45.7% - 48.3%). When both sets of criteria were applied, there were significant associations with bipolarity for a family history of mania or hypomania and multiple past mood episodes. When only the bipolarity specifier was used, there were also significant associations for manic/hypomanic states during treatment with antidepressant drugs, current mixed mood symptoms, and comorbid substance use disorder.

"The bipolar-specifier criteria in comparison with DSM-IV-TR criteria were valid and identified an additional 31% of patients with major depressive episodes who scored positive on the bipolarity criteria," the study authors write. "Family history, illness course, and clinical status, in addition to DSM-IV-TR criteria, may provide useful information for physicians when assessing evidence of bipolarity in patients with major depressive episodes. Such an assessment is recommended before deciding on treatment."

Limitations of this study include lack of random selection of participating centers, widely varying rates of hospitalized patients across countries, retrospective assessment of hypomanic symptoms, cross-sectional design, and lack of a healthy control group.

"It is a sample of convenience, and as such, it represents only patients seeking help for a major depressive episode — important clinically but requiring caution epidemiologically," Dr. Goodwin said. "The cautionary finding is that the increase in cases is associated with the inclusion of more cases with substance misuse, borderline personality disorder, and antidepressant-associated (hypo)mania. We do not understand how this helps treatment approaches."

Regarding strengths of this study, Dr. Goodwin noted that it is relatively large and very widely distributed as an international multicenter study, so the results should be strongly generalizable. It is also based on routine data collected using widely available methods and clinical traditions, so it is meaningful.

"[W]e recommend that, among patients with MDEs [major depressive episodes], the presence of bipolar features, including all those with significant predictive value reported in this study, should be investigated carefully before a decision is made to prescribe antidepressants," the study authors conclude. "If patients exhibit bipolar symptoms that impair everyday functioning, treatment with a mood stabilizer or an atypical antipsychotic may be useful. Treatment approaches for MDD [major depressive disorder] and bipolar disorder differ substantially."

However, Dr. Goodwin noted that there are 2 possible, yet polarized, interpretations of the data.

"First, extending the bipolar disorder diagnosis may be simply unhelpful because it will include cases in whom the main problems are substance misuse or borderline personality," Dr. Goodwin concluded. "Thus, treatment approaches that we know work more or less in bipolar disorder may be less applicable in this extended population. Alternatively, the optimists will say, 'oh no, we are missing the bipolar diagnosis in 3 out of every 4 patients who 'really' have it, and the treatments we have for bipolar disorder will be just as applicable in this extended population.'"

sanofi-aventis supported this study and paid per-patient fees to all investigators who recruited patients. Dr. Goodwin has received honoraria from sanofi-aventis, but not since 2009 or before. He also has disclosed various financial relationships with the National Institute for Health Research, Servier, P1vital, AstraZeneca, BMS, Lundbeck, Cephalon, Janssen-Cilag, Lilly, Schering-Plough, and Wyeth.

Arch Gen Psychiatry. 2011;68:791-799.


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