Antidepressants in Schizophrenia: A Place for Them?

Abstract

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.A convincing amount of evidence is emerging on some previously unknown mechanisms of action beyond the classical neurotransmitter/monoamine receptor theory—findings that may boost research and development in the nearest future. For instance, the novel body of data on the proneuroplastic effect of antidepressants may help us to understand how an add-on antidepressant can improve neurocognition in chronic schizophrenia, and how antidepressant monotherapy can prevent psychosis in high-risk groups. More large RCTs with various combinations are needed to reveal the most feasible antidepressant therapy strategies for schizophrenia.