Abstract: Objectives: The reason why depression may respond poorly to treatment with antidepressant drugs may be connected with the features of bipolarity. Evidence to this effect has accumulated in recent studies of various kinds of depression in mood disorders. Additional evidence for such a connection may be the efficacy of mood-stabilizing drugs in the augmentation of antidepressants in treatment-resistant depression.Methods: This review is based on clinical and psychopharmacological research performed over the past five years. The clinical investigation was based on the response to antidepressants of bipolar depression or to symptoms of hypomania, assessed mainly by the Mood Disorder Questionnaire (MDQ) and the Hypomania Checklist-32 (HCL-32). The psychopharmacological research tested the efficacy of augmentation of antidepressants in treatment-resistant depression by mood-stabilizing drugs of the 1st and 2nd generations.Results: A number of studies have pointed to an association between bipolar depression, or symptoms of hypomania and an inadequate response to antidepressants. Such a connection was also found in the Polish TRES-DEP study which included 1051 depressed patients. Pharmacological studies have demonstrated the efficacy of first generation mood-stabilizing drugs (lithium, carbamazepine) and second generation drugs (quetiapine, olanzapine, risperidone, ziprasidone, lamotrigine) for augmentation of antidepressants in treatment-resistant depression. Some evidence has been presented that mixed depressive episodes may also belong to this category.Conclusions: The results of these clinical and psychopharmacological studies appear to confirm an association between bipolarity and a poor response of depression to treatment with antidepressant drugs.