23 March 2026 : Review article
Antidepressant Augmentation of Antipsychotic Treatment in Schizophrenia: A Narrative Review
Weihao Li ABDEF 1, Biyao Gao
ABDEF 1, Yilin Liu ABDE 1, Weiguo He BDEF 2, Wenhui Zha ABDE 1, Shanshan Du BDEF 1, Yong Zeng AEFG 1, Yunqiao Zhang ABDEF 1*
DOI: 10.12659/MSM.951119
Med Sci Monit 2026; 32:e951119
Introduction
Clinical Features of and Overlap Between Schizophrenia and Depressive Disorders
Biological and Pathophysiological Foundations Relevant to Antidepressant Use
Antidepressant Classes: A Brief Overview
Antidepressants in Schizophrenia: Clinical Strategies and an Overview of the Evidence
Safety Considerations and Drug Interaction Risks in Combined Treatment
Future Directions
Conclusions
References
Table 2 Antidepressants not preferred as first-line augmentation in schizophrenia: main concerns, interaction risks, and monitoring recommendations.
| Antidepressants | Disease | Not recommended drug combinations | Conclusion |
|---|---|---|---|
| Bupropion | Schizophrenia | Bupropion + Clozapine | Combination with clozapine can induce seizures [,]96 |
| Escitalopram | Schizophrenia | Escitalopram + Ziprasidone | Concomitant use with ziprasidone should be approached cautiously due to possible QT prolongation. Close ECG monitoring is recommended, and this regimen is usually not a first-choice strategy [,,–]64 |
| Paroxetine | Schizophrenia | Paroxetine + Fluoxetine + Clozapine | Fluoxetine and paroxetine inhibit the CYP2D6 enzyme, and can increase clozapine’s blood concentration when applied as a combination [–]102 |
| Venlafaxine | Schizophrenia | Venlafaxine + Olanzapine or Clozapine or Risperidone | Concomitant use of venlafaxine with agents that substantially affect metabolic parameters may require caution, with close monitoring of metabolic status advised []107 |
| SGA – second-generation antipsychotic; FGA – first-generation antipsychotic QTc – corrected QT interval; ECG – electrocardiogram; CYP2D6 – cytochrome P4502D6. | |||