The complex relationship between the use of antidepressants and suicidal behaviour is one of the hottest topics of our contemporary psychiatry. Based on the literature, this paper summarizes the author's view on antidepressant-resistant depression and antidepressant-associated suicidal behaviour. Antidepressant-resistance, antidepressant-induced worsening of depression, antidepressant-associated (hypo)manic switches, mixed depressive episode, and antidepressant-associated suicidality among depressed patients are relatively most frequent in bipolar/bipolar spectrum depression and in children and adolescents. As early age at onset of major depressive episode and mixed depression are powerful clinical markers of bipolarity and the manic component of bipolar disorder (and possible its biological background) shows a declining tendency with age antidepressant-resistance/worsening, antidepressant-induced (hypo)manic switches and “suicide-inducing” potential of antidepressants seem to be related to the underlying bipolarity. 1. Introduction Treatment-resistant and particularly antidepressant-resistant major depression (AD-RD) is a great clinical challenge both in the cases of unipolar and bipolar depression [1, 2]. While it is well documented that the optimal clinical response to antidepressants is much rare in bipolar I and II than in unipolar major depression [3–5] only the most recent clinical studies have focused on the boundaries between treatment-resistant unipolar major depressive disorder and bipolar disorder. These studies seem to be more promising in understanding both antidepressant-resistance and antidepressant-associated suicidal behaviour in patients with major mood disorders. 2. Antidepressant Resistance in Major Depressive Episode: Its Relationship with Bipolar Disorder The generally accepted definition of AD-RD refers that the depressed patient does not show a clinically significant response after at least two adequate trials of different classes of antidepressants. In spite of the fact that there are several causes of AD-RD in general [1, 6], one of the most common sources of it is the unrecognized bipolar nature of the “unipolar” major depressive disorder, when the patients receive antidepressant monotherapy—unprotected by mood stabilizers/atypical antipsychotics [4–11]. Unrecognized bipolar depressives are generally treated as “unipolar” major depressives which means that these patients do not receive mood stabilizers [3, 12]. This can result in a very high rate of treatment resistance, which is about two-times higher than in patients with
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