Aim. The aim this pilot study of the all-Polish multicenter TRES-DEP (Treatment Resistant Depression) project was the detection and analysis of bipolar spectrum features in drug-resistant (DR) patients with unipolar depression in comparison with patients who responded to standard antidepressant treatment and remitted (non-drug-resistant-non-DR). Method. Fifty DR patients (group 1) and 50 non-DR patients (group 2), aged 18-65 years, fulfilling ICD10 / DSM-IV criteria for depressive episode or recurrent depressive disorder, were included in the study. The presence of bipolar spectrum (BS) was detected by the Mood Disorder Questionnaire (MDQ) and the Hypomania Checklist Scale (HCL-32). Results. There were statistically significantly more patients fulfilling BS criteria as assessed with MDQ or HCL-32 in group 1 than in group 2 (44% vs 12%, p < 0.001 and 62% vs 34%, p < 0.005 respectively). Significantly more DR patients, compared to non-DR patients, considered their last remission as partial (88% vs 52%, p = 0.001). Non-DR patients had a history of fewer depressive episodes (5.1 +/- 3.8 vs 8.5 +/- 5.0; p = 0.001) and reported a longer time since the last hospitalization (41.9 +/- 17.1 vs 14.8 +/- 26.5 months, p< 0.005). More DR patients fulfilling MDQ BS criteria (MDQ(+)) compared to DR patients without bipolar spectrum considered the last remission as partial or reported lack of remission (100% vs 21%; p < 0.05) or reported treatment nonadherence (41 vs 18%, p = 0.055). More MDQ(+) DR patients had occurrences of suicide attempts (41% vs 18%, p = 0.055) and a mean number of suicide attempts was higher in this group (0.86 +/- 1.28 vs 0.25 +/- 0.59; p < 0.05). Conclusion. The results of the study suggest that misdiagnosed and inadequately treated bipolarity may be one of the main reasons for non-response in the treatment of depression with antidepressant drugs.