Misdiagnosed Hypomanic Symptoms in Patients with Treatment-Resistant Major Depressive Disorder in Italy: Results from the Improve Study

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.