Affective psychosis is a common mental disorder characterized by structural/functional brain abnormalities, which seem to occur also at the early stages of the disease. However, the role of psychotropic medications on brain structure and function in affective first episode psychosis (A-FEP) still remains uncertain. Therefore, with this review we aim to gain more robust understanding regarding the potential effect of pharmacological treatments on the brain in A-FEP patients also experiencing a first manic episode. A search on PuBMed and Web of Science of longitudinal structural and functional Magnetic Resonance Imaging (MRI) as well as Diffusion Tensor Imaging (DTI) studies, exploring the effect of medications on the brain in A-FEP, was conducted. We selected nine studies, three randomized or pseudo-randomized controlled trials and six observational studies. Overall the studies showed that a) mood stabilizers (MS) have no effect on gray matter (GM) volumes and a protective role on white matter (WM) volumes, b) antipsychotics (AP) have an unclear effect on GM volumes and a less potent effect on WM volumes compared to MS and c) both MS and AP tend to normalize brain activation and connectivity. The small sample size, the observational design of the majority of the studies and the different methodological approaches limit the conclusion of this review. Medications seem to have a minor role on structural changes occurring in A-FEP patients during the early stages of the disease, while their effect on brain activation and connectivity seems more pronounced, but far to be conclusive. Copyright © 2020 Elsevier B.V. All rights reserved.