Main Article Content

Nofianti Dewi
Saidah Syamsuddin
Kristian Liaury
Andi Alfian Zainuddin
Haerani Rasyid
Sonny Teddy Lisal


Schizophrenia, Risperidone, MoCA-Ina, Folic Acid, Methylcobalamin, Homocysteine, Cognitive


Background: Cognitive dysfunction in schizophrenic patients has a very high prevalence. Antipsychotic drugs as the main treatment for patients with schizophrenia, provide a symptom response that is not always optimal. Adjunctive treatment with certain vitamins and minerals may be beneficial for people with psychiatric disorders due to a biological mechanism by which these nutrients may improve the cognitive symptoms of schizophrenia. Providing Folic Acid and Methylcobalamin required for homocysteine methylation to methionine and SAM synthesis (S-adenosylmethionine) causes a decrease in homocysteine levels and repairs cell damage and neuronal injury in the brain and improves psychiatric disorders, such as cognitive disorders.

Objectives: Determine the effect of folic acid adjuvant therapy and methylcobalamin on the homocysteine levels and cognitive function of schizophrenic patients receiving risperidone therapy

Methods: The experimental analysis research design by measuring pre- and post-tests with non-random group selection was carried out in January-March 2023 at Dadi RSKD South Sulawesi Province. The number of subjects was 48 according to the inclusion and exclusion criteria. Subjects were divided into 4 groups, namely the control group, folic acid, methylcobalamin, and folic acid plus methylcobalamin. To assess cognitive function, MoCA-Ina was used and homocysteine levels were measured Enzyme-Linked Immunosorbent Assay (ELISA). The Wilcoxon, Mann Whitney and Spearman correlation tests were carried out to see the significance.

Result: Value change of Montreal Cognitive Assessment-Indonesian version (MoCA-Ina) of schizophrenic patients receiving adjuvant therapy plus folic acid + methylcobalamin compared to groups methylcobalamin showed significant results on 4-8 week (p<0.05). Rate change of Homocysteine schizophrenic patients who received adjuvant therapy with folic acid plus methylcobalamin and the methylcobalamin group were more significant  than the control group baseline up to 8 weeks (p<0,05)

Conclusion : Adjuvant therapy with methylcobalamin and folic acid + methylcobalamin is better at improving cognitive function. Administration of adjuvant therapy with methylcobalamin correlated strongly with improving cognitive function and reducing homocysteine levels, whereas adjuvant therapy with folic acid plus methylcobalamin correlated moderately with increasing cognitive function and reducing homocysteine levels.

Abstract 50 | pdf Downloads 12


1. American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5. Auflage). In Washington, DC.
2. Amir, N. (2017). Buku Ajar Psikiatri (edisi 3). Jakarta: Fakultas Kedokteran Universitas Indonesia.
3. Ballon, J., & Stroup, T. S. (2013). Polypharmacy for schizophrenia. Current Opinion in Psychiatry, 26(2), 208–213.
4. Bhattacharya, K. (2015). Cognitive function in schizophrenia: A review. African Journal of Psychiatry (South Africa), 18(1), 1–8.
5. Vuksan-Ćusa, B., Jakovljević, M., Šagud, M., Peleš, A. M., Marčinko, D., Topić, R., ... & Sertić, J. (2011). Metabolic syndrome and serum homocysteine in patients with bipolar disorder and schizophrenia treated with second generation antipsychotics. Psychiatry research, 189(1), 21-25.
6. Chen, P. H., Liu, H. C., Lu, M. L., Chen, C. H., Chang, C. J., Chiu, W. C., ... & Stewart, R. (2019). Homocysteine, rather than age of onset, is a better predictor for cognitive function in older adults with bipolar disorder. International Journal of Geriatric Psychiatry, 34(10), 1473-1480.
7. Crespo, B. H., B & Gonzalez, M. J. (2017). Methionine: Th e One Carbon Metabolic Cycle and its Relation to Pathogenesis. Journal of Clinical Nutrition and Metabolism. 1(12): 1–6
8. Firth, J., Stubbs, B., Sarris, J., Rosenbaum, S., Teasdale, S., Berk, M., & Yung, A. R. (2017). The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis. Psychological medicine, 47(9), 1515-1527.
9. Priebe, S., Savill, M., Wykes, T., Bentall, R., Lauber, C., Reininghaus, U., … Röhricht, F. (2016). Clinical effectiveness and cost-effectiveness of body psychotherapy in the treatment of negative symptoms of schizophrenia: A multicentre randomised controlled trial. Health Technology Assessment, 20(11), 1–100.
10. Roffman, J. L., Lamberti, J. S., Achtyes, E., Macklin, E. A., Galendez, G. C., Raeke, L. H., ... & Goff, D. C. (2013). Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia. JAMA psychiatry, 70(5), 481-489. https://doi:10.1001/jamapsychiatry.2013.900.
11. Stahl, S. M. (2013) Stahl’s Essential Psychopharmacology Neuroscientific Basis and Practical Applications. Fourth. Edited by S. M. Stahl. Britania Raya: Cambridge University Press. Available at: /J-aPMQEACAAJ?hl=id&kptab=overview.
12. Wang, H. F., M.a., J., Liu, J., Tan, M. S., … Yu, J. T. (2016). Serum Folic Levels in Patients with Schizophrenia: A Replication Study and Meta-Analyses. Journal of Science 47(3), 565–581.
13. Wysokiÿski, A., Psikiatri, D., Usia, P., & Lodz, U. K. (2017). SERUM FOLAT DAN HOMOSIstein. 2(1),
14. Hill, M., Shannahan, K., Jasinski, S., Macklin, E. A., Raeke, L., Roffman, J. L., & Goff, D. C. (2011). Folate supplementation in schizophrenia: a possible role for MTHFR genotype. Schizophrenia research, 127(1-3), 41-45.

Most read articles by the same author(s)