Antidepressant Augmentation of Antipsychotic Treatment in Schizophrenia: A Narrative Review

Schizophrenia is a complex psychiatric disorder in which persistent negative symptoms, depressive features, and cognitive difficulties often remain despite adequate antipsychotic treatment. These unmet clinical needs have led to increasing interest in the use of antidepressants as adjunctive therapy. Randomized trials and observational studies suggest that certain selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are associated with modest improvements in negative symptoms, depressive symptoms, affective instability, and overall functioning when combined with second-generation antipsychotics (SGA). Findings from other antidepressant classes have been less consistent, reflecting differences in pharmacological profiles and study designs. Safety considerations, including metabolic risk, drug interactions, and the potential to aggravate psychotic symptoms, remain essential when deciding on augmentation. Although the literature is heterogeneous, available data suggest that antidepressant add-on strategies provide additional benefit for selected patients with inadequate response to antipsychotic monotherapy. Clinical considerations and research priorities are summarized to inform individualized decision-making. This article aims to review the role of antidepressant augmentation of antipsychotic treatment in patients with schizophrenia.