The effect of Ascorbic Acid as supplementary treatment with risperidone in controlling the symptoms of schizophrenia: A double-blind, placebo-controlled clinical trial

Document Type: Research Paper

Authors

Department of Psychiatry, University of Welfare and Research Sciences, Tehran, Iran

Abstract

Background and Objective: Considering the hypothesis of the effects of the use of antioxidants such as ascorbic acid on the improvement of oxidative stress induced by schizophrenia, the present study was designed to investigate the effect of ascorbic acid as an adjunctive therapy with risperidone in controlling the symptoms of schizophrenia.
Materials and Methods: This randomized clinical trial was conducted on patients with schizophrenia admitted to Tehran's Razi hospital of psychiatry in 2018. The patients were divided into control and intervention groups. The group treated with ascorbic acid received this drug daily at 500 mg twice daily and the placebo group received a similar drug, similar to ascorbic acid, at the same rate for 4 months. The PANSS (Positive & Negative Symptom Scale) questionnaire was used to determine the status of the positive and negative symptoms and the SCORS (Schizophrenia Cognition Rating Scale) questionnaire was used to determine the cognitive status at the end of weeks 8 and 16 when entering the study. Data were analyzed using paired t-test and Wilcoxon in SPSS 20 software.
Results: The effect of ascorbic acid on the positive and negative symptoms of patients at the 8th and 16th weeks showed that after eight weeks of treatment, among the positive symptoms, conceptual disorganization, excitement, hostility and grandiosity, among the negative symptoms, blunted affect has had a significant improvement relative to before intervention. After 16 weeks of treatment, except difficulty in abstract thinking, all of the symptoms showed a significant improvement compared with the symptoms of the patients before the study. Compared to ascorbic acid, the effect of placebo on all of the positive and negative symptoms and other symptoms in most cases was not significant. Regarding the effect of ascorbic acid on the cognitive symptoms of patients in the 8th and 16th week, there was no significant difference in the few numbers of cognitive symptoms in the eighth week, although after eight weeks, overall cognitive symptoms were significantly improved (p<0.05). In addition, after 16 weeks of treatment, almost all of the parameters of the cognitive symptoms and the total of cognitive symptoms were significantly improved compared to the pre-intervention (p<0.01). Compared to ascorbic acid, the effect of placebo on cognitive symptoms in most cases was not significant (P >0.05).
Conclusion: The results of this study showed that ascorbic acid, having its antioxidant effects after sixteen weeks of treatment, reduced the patients' positive and negative symptoms and their cognitive symptoms. Compared to ascorbic acid, the effect of placebo on cognitive symptoms and positive and negative symptoms was not significant in most cases.

Keywords


  1. Bahmany N, Zandi Ghashghaee K, Khosravi S. A comparison between effectiveness of three types of music on memory activity and sustained attention in schizophrenic patients. Iranian South Medical Journal 2014; 17 (4) :706-715
  2. Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet 2016;388(10039):86-97.
  3. Gold C, Heldat TO, Dahle T, et al. Music therapy for schizophrenia of schizophrenia - Like illnesses. The Cochrane Database of Systematic Reviews 2005; 18(2): 004025.
  4. Rafiee Vardanjani L, Parvin N, Dehkordi SF, Shahinfard N, Morte S, Ansari Samani R. The effects of Portulaca oleracea L (purslane) on psychologic symptoms and malondialdehyde level in schizophrenic patients. The Scientific Journal of Kurdistan University of Medical Sciences 2013, 18(4): 28-34
  5. Altuntas I, Aksoy H, Coskun I, Caykoylu A, Akcay F. Erythrocyte superoxide dismutaseand glutathione peroxidase activities, and malondialdehyde and reduced glutathione levels inschizophrenic patients. Clinical Chemistry and Laboratory Medicine 2000;38:1277-82.
  6. Kuloglu M, Ustundag B, Atmaca M, Canatan H, Tezcan AE, Cinkilinc N. Lipidperoxidation and antioxidant enzyme levels in patients with schizophrenia and bipolardisorder. Cell Biochemistry and Function 2002;20:171-5.
  7. Pavlović D, Tamburić V, Stojanović I, Kocić G, Jevtović T, Djordjević V. Oxidative stressas marker of positive symptoms in schizophrenia. Facta Universitatis Series: Medicine and Biology 2002;9:157-61.
  8. Zhang XY, Tan YL, Cao LY, Wu GY, Xu Q, Shen Y, and et al. Antioxidant enzymes andlipid peroxidation in different forms of schizophrenia treated with typical and atypicalantipsychotics. Schizophrenia Research 2006;81:291-300.
  9. Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence baseand therapeutic implications. The International Journal of Neuropsychopharmacology 2008;11:851-76.
  10. Ghosian Moghadam MH, Ansari I, Roghani M, Ghanem A, Mehdizade N. The Effect of Oral Administration of Hypericum Perforatum on Serum Glucose and Lipids, Hepatic Enzymes and Lipid Peroxidation in Streptozotocin-Induced Diabetic Rats. Galen Medical Journal 2017; 6(4):319-329.
  11. Pazdro R, Burgess JR. The role of vitamin E and oxidative stress in diabetes complications. Mechanisms of Ageing and Development 2010;131:276-86.
  12. Ghosian Moghaddam MH, Ansari I, Roghani M, Moradi M. The Effects of Origanum Majorana on Oxidative Stress and Histopathology of Renal Tissue among Streptozotocin-Induced Diabetic Rats. Thrita 2013; 2(3): 29-34.
  13. Stohs S. The role of free radicals in toxicity and disease. Journal of Basic and Clinical Physiology and Pharmacology 1995;6:205-28.
  14. Raffa M, Mechri A, Othman LB, Fendri C, Gaha L, Kerkeni A. Decreased glutathione levels and antioxidant enzyme activities in untreated and treated schizophrenic patients. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2009;33:1178-83.
  15. Kunz M, Gama CS, Andreazza AC, Salvador M, Ceresér KM, Gomes FA, et al. Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2008;32:1677-81.
  16. Magalhães PV, Dean O, Andreazza AC, Berk M, Kapczinski F. Antioxidant treatments for schizophrenia. Cochrane Database of Systematic Reviews 2016;2:CD008919.
  17. Wang J, Zhang Z, Huang R. Regulation of ascorbic acid synthesis in plants. Plant Signaling & Behavior. 2013;8(6):e24536.
  18. Weiss WP. A 100-Year Review: From ascorbic acid to zinc-Mineral and vitamin nutrition of dairy cows. Journal of Dairy Science 2017;100(12):10045-10060.
  19. Grosso G, Bei R, Mistretta A, Marventano S, Calabrese G, Masuelli L, et al. Effects of vitamin C on health: a review of evidence. Frontiers in Bioscience (Landmark Ed) 2013;18:1017-29.
  20. Pohanka M, Pejchal J, Snopkova S, Havlickova K, Karasova JZ, Bostik P, et al. Ascorbic acid: an old player with a broad impact on body physiology including oxidative stress suppression and immunomodulation: a review. Mini-Reviews in Medicinal Chemistry 2012;12(1):35-43.
  21. Akram NA, Shafiq F, Ashraf M. Ascorbic Acid-A Potential Oxidant Scavenger and Its Role in Plant Development and Abiotic Stress Tolerance. Frontiers in Plant Science 2017;8:613.
  22. Suboticanec K, Folnegović-Smalc V, Korbar M, Mestrović B, Buzina R. Vitamin C status in chronic schizophrenia. Biological Psychiatry 1990;28(11):959-66.
  23. Damazio LS, Silveira FR, Canever L, Castro AA, Estrela JM, Budni J, et al. The preventive effects of ascorbic acid supplementation on locomotor and acetylcholinesterase activity in an animal model of schizophrenia induced by ketamine. The Anais da Academia Brasileira de Ciências 2017;89(2):1133-1141.
  24. Magalhães PV, Dean O, Andreazza AC, Berk M, Kapczinski F. Antioxidant treatments for schizophrenia. The Cochrane Database of Systematic Reviews 2016;2:CD008919.
  25. Bentsen H, Osnes K, Refsum H, Solberg DK, Bøhmer T. A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia. Translational Psychiatry 2013;3(12):e335-.
  26. Heiser P, Sommer O, Schmidt AJ, Clement HW, Hoinkes A, Hopt UT, et al. Effects of antipsychotics and vitamin C on the formation of reactive oxygen species. Journal of Psychopharmacology 2010;24(10):1499-504.
  27. Hoffer LJ. Vitamin therapy in schizophrenia. The Israel Journal of Psychiatry and Related Sciences 2008;45(1):3-10.
  28. Sivrioglu EY, Kirli S, Sipahioglu D, Gursoy B, Sarandöl E. The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2007;31(7):1493-9.
  29. Young J, McKinney SB, Ross BM, Wahle KW, Boyle SP. Biomarkers of oxidative stress in schizophrenic and control subjects. Prostaglandins Leukot Essent Fatty Acids 2007;76(2):73-85.
  30. Dakhale GN, Khanzode SD, Khanzode SS, Saoji A. Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia. Psychopharmacology 2005;182(4):494-8.
  31. Dadheech G, Mishra S, Gautam S, Sharma P. Oxidative stress, α-tocopherol, ascorbic acid and reduced glutathione status in schizophrenics. Indian Journal of Clinical Biochemistry 2006;21(2):34-38.
  32. Dakhale G, Khanzode S, Khanzode S, Saoji A, Khobragade L, Turankar A. Oxidative damage and schizophrenia: the potential benefit by atypical antipsychotics. Neuropsychobiology 2004;49(4):205-9.
  33. Castagné V, Rougemont M, Cuenod M, Do KQ. Low brain glutathione and ascorbic acid associated with dopamine uptake inhibition during rat's development induce long-term cognitive deficit: relevance to schizophrenia. Neurobiology of Disease 2004;15(1):93-105.
  34. Arvindakshan M, Ghate M, Ranjekar PK, Evans DR, Mahadik SP. Supplementation with a combination of omega-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia. Schizophrenia Research 2003;62(3):195-204.
  35. Michael N, Sourgens H, Arolt V, Erfurth A. Severe tardive dyskinesia in affective disorders: treatment with vitamin E and C. Neuropsychobiology 2002;46 Suppl 1:28-30.
  36. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13(2):261-76.
  37. Mazhari S1, Ghafaree-Nejad AR2, Soleymani-Zade S3, Keefe RSE. Validation of the Persian version of the Schizophrenia Cognition Rating Scale (SCoRS) in patients with schizophrenia. Asian Journal of Psychiatry 2017;27:12-15.
  38. Salehi B, Vakilian K, Ranjbar A. Relationship of Schizophrenia with Lipid Peroxidation, Total Serum Antioxidant Capacity and Thiol Groups. Iranian Journal of Psychiatry and Clinical Psychology 2008; 14 (2):140-145.