[What to do in the case of a failed first antidepressive trial? To switch or to augment?]

Since SSRIs and other new antidepressant agents entered the market, the possibilities to treat depression improved substantially but 50 percent of major depressives do not respond to the first, and 25-35 percent do not respond even to the second antidepressant trial. Pharmacotherapy-resistant depression is a multicausal phenomenon. Along with its well-known risk-factors, investigations of the past decade have revealed that unrecognised or hidden (sub syndromal or subthreshold) bipolarity is one of the most frequent causes of treatment resistance. In the case of bipolar depression (either as a part of syndromal bipolar I or II disorder or a subsyndromal manifestation) antidepressant mono therapy should be avoided and, instead of it, the administration of a mood stabilizer (primarily lithium and lamotrigine) or certain atypical antipsychotics (preferably quetiapine, aripiprazole and cariprazine) is recommended. If anti depressant is inevitably necessary in bipolar depression, we should use it always in combination with mood stabilizers or atypical antipsychotics. After the first failed antidepressant trial, augmentation with lithium, lamotrigine, or anti psychotics is recommended at first, and if this is not successful switching the antidepressant is recommended. Keywords: antidepressants; augmentation, treatment resistance; bipolar disorder; bipolar spectrum; switch the anti depressant, unipolar major depressive disorder.