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Association between bipolar spectrum features and treatment outcomes in outpatients with major depressive disorder.

ABSTRACT: It has been suggested that patients with major depressive disorder (MDD) who display pretreatment features suggestive of bipolar disorder or bipolar spectrum features might have poorer treatment outcomes.To assess the association between bipolar spectrum features and antidepressant treatment outcome in MDD.Open treatment followed by sequential randomized controlled trials.Primary and specialty psychiatric outpatient centers in the United States.Male and female outpatients aged 18 to 75 years with a DSM-IV diagnosis of nonpsychotic MDD who participated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.Open treatment with citalopram followed by up to 3 sequential next-step treatments.Number of treatment levels required to reach protocol-defined remission, as well as failure to return for the postbaseline visit, loss to follow-up, and psychiatric adverse events. For this secondary analysis, putative bipolar spectrum features, including items on the mania and psychosis subscales of the Psychiatric Diagnosis Screening Questionnaire, were examined for association with treatment outcomes.Of the 4041 subjects who entered the study, 1198 (30.0%) endorsed at least 1 item on the psychosis scale and 1524 (38.1%) described at least 1 recent maniclike/hypomaniclike symptom. Irritability and psychoticlike symptoms at entry were significantly associated with poorer outcomes across up to 4 treatment levels, as were shorter episodes and some neurovegetative symptoms of depression. However, other indicators of bipolar diathesis including recent maniclike symptoms and family history of bipolar disorder as well as summary measures of bipolar spectrum features were not associated with treatment resistance.Self-reported psychoticlike symptoms were common in a community sample of outpatients with MDD and strongly associated with poorer outcomes. Overall, the data do not support the hypothesis that unrecognized bipolar spectrum illness contributes substantially to antidepressant treatment resistance.

SUBMITTER: Perlis RH

PROVIDER: S-EPMC3794668 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Association between bipolar spectrum features and treatment outcomes in outpatients with major depressive disorder.

Perlis Roy H RH Uher Rudolf R Ostacher Michael M Goldberg Joseph F JF Trivedi Madhukar H MH Rush A John AJ Fava Maurizio M

Archives of general psychiatry 20101206 4

<h4>Context</h4>It has been suggested that patients with major depressive disorder (MDD) who display pretreatment features suggestive of bipolar disorder or bipolar spectrum features might have poorer treatment outcomes.<h4>Objective</h4>To assess the association between bipolar spectrum features and antidepressant treatment outcome in MDD.<h4>Design</h4>Open treatment followed by sequential randomized controlled trials.<h4>Setting</h4>Primary and specialty psychiatric outpatient centers in the ...[more]

PMID: 21135313

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Project description:Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of the present study was to determine whether this shared genetic liability influences clinical presentation.A polygenic risk score for bipolar disorder, derived from a large genome-wide association meta-analysis, was generated for each subject of European-American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort. A hypothesis-driven approach was used to test for association between bipolar disorder risk score and features of depression associated with bipolar disorder in the literature. Follow-up analyses were performed in two additional cohorts.A generalized linear mixed model including seven features hypothesized to be associated with bipolar spectrum illness was significantly associated with bipolar polygenic risk score [F = 2.07, degrees of freedom (df) = 7, p = 0.04]. Features included early onset, suicide attempt, recurrent depression, atypical depression, subclinical mania, subclinical psychosis, and severity. Post-hoc univariate analyses demonstrated that the major contributors to this omnibus association were onset of illness at age ? 18 years [odds ratio (OR) = 1.2, p = 0.003], history of suicide attempt (OR = 1.21, p = 0.03), and presence of at least one manic symptom (OR = 1.16, p = 0.02). The maximal variance in these traits explained by polygenic score ranged from 0.8% to 1.1%. However, analyses in two replication cohorts testing a five-feature model did not support this association.Bipolar genetic loading appeared to be associated with bipolar-like presentation in major depressive disorder in the primary analysis. However, the results were at most inconclusive because of lack of replication. Replication efforts were challenged by different ascertainment and assessment strategies in the different cohorts. The methodological approach described here may prove useful in applying genetic data to clarify psychiatric nosology in future studies.

Dataset Information

Association between bipolar spectrum features and treatment outcomes in outpatients with major depressive disorder.

Publications

Association between bipolar spectrum features and treatment outcomes in outpatients with major depressive disorder.

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