The aim of this review is to appraise the data from available randomized clinical trials (RCT) regarding the possible combinations of neuroleptic and non-antipsychotic treatment which could enhance antipsychotic therapy efficacy whilst simultaneously addressing somatic symptoms in individuals with schizophrenia. A systematic search of the PubMed database up to February 2022 was conducted. Inclusion criteria: randomized controlled trials using augmentation therapy in chronic schizophrenia in adults, written in English, and only studies with psychometric assessments of schizophrenia were incorporated. Exclusion criteria: non-clinical, first episode of schizophrenia, patients on medication other than antipsychotics augmented, and not adjunctive therapy. Overall, 37 studies of 1931 patients with schizophrenia who received a combination of antipsychotic medication with other drugs were selected. A statistically significant reduction of negative and positive symptoms of schizophrenia, measured with the PANSS scale, when using a combination of antipsychotic treatment along with aspirin, simvastatin, N-acetylcysteine, or pioglitazone was found. A combination of antipsychotic medication with aspirin, simvastatin, N-acetylcysteine, or pioglitazone seems to be effective in the reduction of symptoms of schizophrenia in adults, but long-term studies are required to confirm this effect.