Antidepressants in Schizophrenia: A Place for Them?

Antipsychotic monotherapy is often insufficient to achieve optimal outcome in schizophrenia. One of the numerous adjunctive psychopharmacological strategies proposed to overcome this drawback is a combination of an antipsychotic with an antidepressant. Existing evidence on the efficacy of such combination is ambiguous and varies by syndrome domains and antidepressant classes and—within a class—by individual compounds. The most dependable data favor—as a group—receptor-blocking antidepressants. Of these, mirtazapine demonstrates probably the most consistent beneficial effects, in particular for negative symptoms and cognitive deficits. While current guidelines warn about possible antidepressant-provoked psychotic exacerbation, no data today support these reservations, at least in chronic schizophrenia and when a contemporaneous antipsychotic therapy continues. Moreover, one randomized controlled trial (RCT) revealed an additive antipsychotic effect of an adjunctive antidepressant (mirtazapine) and, according to a recently published large cohort study concomitant antidepressants can reduce suicide rates and overall mortality of patients with schizophrenia. It appears hence that caution regarding the add-on antidepressant use recommended by current guidelines can be soon softened. Due to scarcity of data, conservative use of antidepressants may, however, be still justifiable in acute schizophrenia. If an antipsychotic-antidepressant combination is to be prescribed, a thorough knowledge of pharmacodynamic and pharmacokinetic (especially, regarding several CYP450 liver enzymes) interactions is essential to avoid adverse effects and complications.