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Ardiansyah, Syamsuddin Saidah
Liaury Kristian
Seweng Arifin
Limoa Erlyn
Bahrun Uleng
Lisal T Sonny


interleukin-6, risperidone, schizophrenia, statins


Background: Schizophrenia is a mental illness caused by gene-environment interaction. There is a role for dysregulation of inflammation in the pathogenesis of schizophrenia which is characterized by increased levels of interlukin-6. The use of first-generation antipsychotics can cause negative symptoms of schizophrenia. Treatment using anti-inflammatory adjuvants has the potential to have a better effect by reducing negative symptoms. Statins have been introduced as anti-inflammatory agents that can be used as adjuvant therapy for schizophrenia.

Objective: To determine the effect of adjuvant statin therapy on IL-6, lipid profile and clinical symptoms in schizophrenic patients treated with risperidone.

Methods: This study is an experimental study with a randomized clinical trial design with a double-blind approach. The study was conducted on 36 schizophrenic patients who were treated at Dadi Regional Special Hospital, South Sulawesi Province. Patients were randomized into 2 groups: 18 patients were given 4-6 mg/day of risperidone and 40 mg/day of oral simvastatin adjuvant therapy for 8 weeks (treatment) and 18 patients were given 4-6 mg/day of risperidone (control). A total of 18 healthy individuals were used to control IL-6 levels. IL-6 levels and lipid profiles were measured in the form of triglyceride, cholesterol, HDL and LDL levels before therapy and the 8th week. PANSS clinical symptoms were measured before therapy, week 4 and 8 after therapy. Data were analyzed using the independent sample t test, Mann Whitney, Wilcoxon, Spearman correlation and chi square.

Results: IL-6 levels in schizophrenic patients were significantly higher than healthy individuals and IL-6 levels after both therapy with and without statin adjuvants were not significantly different from IL-6 levels in healthy individuals. There was a significant decrease in serum IL-6 levels in the treatment group, but not in the control group. Nonetheless, changes in serum IL-6 levels after 8 weeks of therapy were not significantly different between the treatment and control groups. There was a significant change in lipid profile in the treatment group, but not in the control. Lipid profile changes after 8 weeks of therapy differed significantly between the treatment and control groups. In the treatment group there was a decrease in triglyceride, cholesterol and LDL levels and an increase in HDL levels. There was a significant improvement in the clinical symptoms of schizophrenia patients in the treatment and controls at the 4th and 8th week of therapy. There were significant differences in changes in clinical symptoms between the treatment and the controls. IL-6 levels in schizophrenic patients receiving statin adjuvant therapy were not significantly associated with clinical symptoms.

Conclusion: Simvastatin adjuvant therapy orally 40 mg/day for 8 weeks can reduce clinical symptoms, reduce serum IL-6 levels and clinical symptoms better than therapy with risperidone alone.

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1. Andrade, C. (2018). The Use of Statins for Antipsychotic Augmentation in Schizophrenia. The Journal of Clinical Psychiatry, 79(5).
2. Aslani, S., Razi, B., Imani, D., Mohammadi, K., Reiner, T., Željko, J., & Sahebkar, A. (2023). Effect of Statins on the Blood Lipid Profile in Patients with Different Cardiovascular Diseases: A Systematic Review with Meta-analysis of Randomized Clinical Trials. Curr Med Chem, 30(32).
3. Berthold, H. K., Berneis, K., Mantzoros, C. S., Krone, W., & Gouni-Berthold, I. (2013). Effects of simvastatin and ezetimibe on interleukin-6 and high-sensitivity C-reactive protein. Scandinavian Cardiovascular Journal, 47(1), 20–27.
4. Bushe, C. J., Taylor, M., & Haukka, J. (2010). Mortality in schizophrenia: a measurable clinical endpoint. Journal of psychopharmacology (Oxford, England), 24(4), 17–25.
5. Challa, F., Seifu, D., Sileshi, M., Getahun, T., Geto, Z., Kassa, D., Alemayehu, M., Mesfin, M., Fekadu, A., & Woldeamanuel, Y. (2021). Serum level of highly sensitive C-reactive protein and IL − 6 markers in patients with treatment-resistant schizophrenia in Ethiopia: a comparative study. BMC Psychiatry, 21(1), 4–11.
6. Chaudhry, I. B., Husain, N., Husain, M. O., Hallak, J., Drake, R., Kazmi, A., Rahman, R. ur, Hamirani, M. M., Kiran, T., Mehmood, N., Stirling, J., Dunn, G., & Deakin, B. (2013). Ondansetron and simvastatin added to treatment as usual in patients with schizophrenia: study protocol for a randomized controlled trial. Trials, 14, 1–9.
7. Cho, M., Lee, T. Y., Kwak, Y. Bin, Yoon, Y. B., Kim, M., & Kwon, J. S. (2019). Adjunctive use of anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials. Australian and New Zealand Journal of Psychiatry, 53(8), 742–759.
8. Dawidowski, B., Górniak, A., Podwalski, P., Lebiecka, Z., Misiak, B., & Samochowiec, J. (2021). The Role of Cytokines in the Pathogenesis of Schizophrenia. Journal of Clinical Medicine, 10(3), 262–268.
9. Feng, Z., Zhang, Y., You, X., Zhang, W., Ma, Y., Long, Q., Liu, Z., Hao, W., Zeng, Y., & Teng, Z. (2020). Effects of risperidone on blood levels of interleukin-6 in schizophrenia: A meta-analysis. Medicine, 99(15), 19694.
10. Kim, S. W., Kang, H. J., Jhon, M., Kim, J. W., Lee, J. Y., Walker, A. J., ... & Berk, M. (2019). Statins and inflammation: new therapeutic opportunities in psychiatry. Frontiers in psychiatry, 10, 103.
11. Lumbantoruan, S. D. (2019). Hubungan Antara Fungsi Kognitif dan Kadar Interleukin-6 (IL-6) pada Orang dengan Skizofreni Suku Batak. Sumatera: Universitas SUmatera Utara.
12. MacDowell, K. S., García-Bueno, B., Madrigal, J. L. M., Parellada, M., Arango, C., Micó, J. A., & Leza, J. C. (2013). Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation. International Journal of Neuropsychopharmacology,16(1),121–135.
13. Madaan, V. (2009). Risperidone: a review of efficacy studies in adolescents with schizophrenia. Drugs of today (Barcelona, Spain: 1998), 45(1), 55–62.
14. McNeil, S., Gibbons, J., & Cogburn, M. (2022). Risperidone. Available:
15. Meo, M. L., Machin, A., & Hasmono, D. (2021). Effect of Simvastatin in Serum Interleukin-6 Level in Patients with Acute Ischemic Stroke. Folia Medica Indonesiana, 56(3), 165.
16. Neelamekam, S., Nurjono, M., & Lee, J. (2014). Regulation of interleukin-6 and leptin in schizophrenia patients: A preliminary analysis. Clinical Psychopharmacology and Neuroscience, 12(3), 209–214.
17. Park, J. W., Park, K. H., Lee, J. E., Kim, Y. M., Lee, S. J., & Cheon, D. H. (2019). Antibody Microarray Analysis of Plasma Proteins for the Prediction of Histologic Chorioamnionitis in Women with Preterm Premature Rupture of Membranes. Reproductive Sciences, 26(11), 1476–1484.
18. Postma, T. S., Lyliana G, N., Maya J L, S., Marc M, B., Peter, M., Erna van’t, H., Selene R T, V., Marieke J H, B., & Iris E C, S. (2017). Statins as an Adjuvant Therapy for Psychotic Disorders: Current Evidence with a Systematic Overview of Double-Blind Placebo Controlled Trials. Journal of Brain Disorders, 1(1), 12–19.
19. Riset Kesehatan Dasar (Riskesdas). (2018). Persebaran Prevalensi Skizofrenia/Psikosis di Indonesia. Jakarta: Kementrian Kesehatan RI.
20. Riskesdas. (2018). Laporan Provinsi Sulawesi Selatan Riskesdas 2018. In Badan Penelitian Dan Pengembangan Kesehatan 110, (9).
21. Saidah, S., Sonny, L. T., Lilik, H., Burhanuddin, B., Haerani, R., & Wempy, T. (2021). Levels of interleukin 6 as a predictor of metabolic syndrome in schizophrenic patients receiving combination therapy of typical and atypical antipsychotics. Open Access Macedonian Journal of Medical Sciences, 9, 600–607.
22. Shalehuddin, M., Adi, A. C., M, H. M., & Handajani, R. (2019). Relationship between Duration of Illness and Onset with PANSS and Interleukin-6 in Schizophrenia. J Brain Res, 2(2), 109.
23. Shen, H., Li, R., Yan, R., Zhou, X., Feng, X., Zhao, M., & Xiao, H. (2018). Adjunctive therapy with statins in schizophrenia patients: A meta-analysis and implications. Psychiatry Research, 262, 84–93.
24. Shuhaili, M. F. R. M. A., Samsudin, I. N., Stanslas, J., Hasan, S., & Thambiah, S. C. (2017). Effects of Different Types of Statins on Lipid Profile: A Perspective on Asians. Int J Endocrinol Metab, 15(2), 1–12.
25. Tajik-Esmaeeli, S., Moazen-Zadeh, E., Abbasi, N., Shariat, S. V., Rezaei, F., Salehi, B., & Akhondzadeh, S. (2017). Simvastatin adjunct therapy for negative symptoms of schizophrenia: A randomized double-blind placebo-controlled trial. International Clinical Psychopharma-cology, 32(2), 87–94.
26. Talreja, O., Kerndt, C., & Cassagnol, M. (2022). Simvastatin. StatPearls Publishing LLC.
27. Ward, N. C., Watts, G. F., & Eckel, R. H. (2019). Statin Toxicity: Mechanistic Insights and Clinical Implications. Circulation Research, 124(2), 328–350.
28. World Health Organization. (2017). Mental health ATLAS 2017 state profile. Geneva: World Health Organization. World Health Organization; WHO.

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