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Misdiagnosed hypomanic symptoms in patients with treatment-resistant major depressive disorder in Italy: results from the improve study.

ABSTRACT: BACKGROUND:Undiagnosed and therefore inadequately treated hypomanic symptoms may be a leading cause of drug resistance in depression diagnosed as unipolar (major depressive disorder, MDD). The purpose of the IMPROVE study was to identify the rate of misdiagnoses in patients with treatment-resistant MDD by screening for the presence of previous hypomanic episodes, and to study the characteristics of those patients with a positive history of hypomania. METHODS:Patients attending 29 psychiatric units throughout Italy with a diagnosis of MDD who were resistant to anti-depressant treatment were included in this multicentre, observational single visit study. The Hypomania Checklist 32 (HCL-32) was administered to detect underlying bipolarity. RESULTS:Among the 466 enrolled patients, 256 (57.40%) were positive at screening for a previous hypomanic episode (HCL-32 ?12), therefore suggesting a misdiagnosis. These patients scored higher than those with a negative history in both the "active/elated hypomania" (11.27±3.11 vs 3.57±3.05; P<0.0001) and "irritable/risk-taking hypomania" (2.87±2.03 vs 2.06±1.73; P<0.001) HCL-32 sub-scales. Patients with a positive history of hypomania were younger, had a higher number of previous depressive episodes and a higher frequency of comorbid conditions compared to those with a negative history. CONCLUSIONS:This study suggests that screening for hypomania in MDD-resistant patients facilitates identification of a notable proportion of undiagnosed cases of bipolar spectrum disorder. Patients with a positive history of hypomania at screening had a demographic/clinical bipolar-like profile that included young age, higher number of previous depressive episodes and higher frequency of comorbid conditions. They also had both higher active and irritable hypomania symptom scores.

SUBMITTER: Francesca MM

PROVIDER: S-EPMC3996725 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Misdiagnosed hypomanic symptoms in patients with treatment-resistant major depressive disorder in Italy: results from the improve study.

Francesca Moro Maria MM Efisia Lecca Maria LM Alessandra Ghillani M GM Marianna Alacqua A Giovanni Carta Mauro CM

Clinical practice and epidemiology in mental health : CP & EMH 20140307

<h4>Background</h4>Undiagnosed and therefore inadequately treated hypomanic symptoms may be a leading cause of drug resistance in depression diagnosed as unipolar (major depressive disorder, MDD). The purpose of the IMPROVE study was to identify the rate of misdiagnoses in patients with treatment-resistant MDD by screening for the presence of previous hypomanic episodes, and to study the characteristics of those patients with a positive history of hypomania.<h4>Methods</h4>Patients attending 29 ...[more]

PMID: 24761153

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Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:Sub-threshold hypomanic symptoms are common in major depressive disorder. This study evaluated the prevalence, the clinical and sociodemographic correlates, and the overall and differential effects of the presence/absence of sub-threshold hypomanic symptoms at baseline on acute-phase treatment outcomes with bupropion-plus-escitalopram combination, escitalopram monotherapy, and venlafaxine-plus-mirtazapine combination. Combining medications to enhance depression outcomes (CO-MED) trial participants (n = 665) were designated as sub-threshold hypomanic symptoms present (Altman Self-Rating Mania Scale score (ASRM) ≥ 1) or absent (ASRM = 0) and compared on clinical and sociodemographic features and remission rates. Participants with sub-threshold hypomanic symptoms (n = 335/665, 50.4%) were more likely to be black and non-Hispanic, have comorbid medical and psychiatric disorders, experience longer index episodes, and report lower depression severity and psychosocial impairment. Intent-to-treat remission rates were lower overall (absent = 42.7%, present = 34.0%, p = 0.02), with escitalopram monotherapy (absent = 45.8%, present = 31.6%, p = 0.03), and with venlafaxine-XR-plus-mirtazapine combination (absent = 44.4%, present = 30.1%, p = 0.03) but not with bupropion-plus-escitalopram combination (absent = 37.7%, present = 40.0%, p = 0.73). Participants without sub-threshold hypomanic symptoms were more likely to remit than those with such symptoms overall [odds ratio (OR) = 1.49], with escitalopram monotherapy (OR = 1.71), and with venlafaxine-plus-mirtazapine combination (OR = 1.97) but not with bupropion-plus-escitalopram combination (OR = 0.96), even after controlling for baseline depression severity, psychosocial impairment, and number of comorbid psychiatric disorders. Sub-threshold hypomanic symptoms (found in about 50% of patients in this report) were associated with lower remission rates with escitalopram monotherapy and with venlafaxine-plus-mirtazapine combination but not with the bupropion-plus-escitalopram combination.

Dataset Information

Misdiagnosed hypomanic symptoms in patients with treatment-resistant major depressive disorder in Italy: results from the improve study.

Publications

Misdiagnosed hypomanic symptoms in patients with treatment-resistant major depressive disorder in Italy: results from the improve study.

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