Ondansetron Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder: A Randomized Placebo-Controlled Clinical Trial
PDF
HTML

Keywords

Obsessive-Compulsive Disorder
Ondansetron
Selective Serotonin Reuptake Inhibitor
Yale – Brown

How to Cite

Sepehrmanesh , Z. ., Adel, M. ., Ahmadvand , A. ., & Sehat , M. . (2020). Ondansetron Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder: A Randomized Placebo-Controlled Clinical Trial. Iranian Red Crescent Medical Journal, 22(5). Retrieved from https://www.ircmj.com/index.php/IRCMJ/article/view/591

Abstract

Background: Serotonin and dopamine are involved in the development of obsessive-compulsive disorder (OCD). Approximately 40% of OCD patients do not respond to the first-line therapy of treatment using selective serotonin reuptake inhibitors. Reportedly, the response to the treatment is increased by enhancing dopamine blockers.

Objectives: The purpose of this study was to evaluate the efficacy and immunogenicity of ondansetron as a booster in the treatment of OCD patients.

Methods: The present double-blind, randomized clinical trial (RCT) was conducted on 40 patients (16 males and 24 females) aged 18 to 60 years who met the DSM-V-TR-based OCD diagnostic criteria and had a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The patients were randomized to receive standard treatment and ondansetron (8 mg/day) or placebo for 12 weeks. They were examined using Y-BOCS and side-effect checklist at baseline, fourth, eighth, and twelfth weeks.

Results: The patients in both groups were homogeneous and comparable in terms of age, marital sex status, type of obsession, anxiety, depression, age at the onset of disease, and the duration of disease. The Y-BOCS scores in the intervention and placebo groups were 27.15 ± 3.94 vs. 26.15 ± 4.94 at baseline, 25.40 ± 3.75 vs. 25.00 ± 4.79 in the fourth week, 20.85 ± 3.69 vs. 24.05 ± 4.97 (P = 0.026) in the eighth week, and 17.95 ± 3.43 vs. 21.65 ± 4.85 (P = 0.008) in the twelfth week, respectively. Significant changes occurred between the two groups at weeks 8 and 12; the difference between the two groups was significant (P = 0.015), whereas no significant difference was observed between the two groups before week 8.

Conclusions: This 12-week, double-blind, and randomized clinical trial showed that ondansetron was a booster agent with a significant effect on patients with moderate to severe OCD. This study also showed that ondansetron is generally well tolerated by OCD patients. The response to the treatment also increased from the eighth week of treatment onwards. The severity of the disease was decreased at the end of the ondansetron intervention. The adjunct ondansetron treatment was recommended for OCD patients

PDF
HTML

References

  1. Sadock BJ, Sadock VA. Synopsis of Psychiatry. 10th ed. Philadelphia: Lippincott Williams & Wilkins; 2015. 604 p.
  2. Murray CJL, Lopez AD. Global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries and risk factors in 1990 and projected to 2020. Harvard: World Health Organization; 1996.
  3. Pigott TA. Obsessive-compulsive disorder: symptom overview and epidemiology. Bull Menninger Clin. 1998;62(4 Suppl A):A4-32. [PubMed: 9810775].
  4. Koran LM. Quality of Life in Obsessive-Compulsive Disorder. Psychiatric Clinics of North America. 2000;23(3):509-17. doi: 10.1016/s0193-953x(05)70177-5.
  5. Eisen JL, Mancebo MA, Pinto A, Coles ME, Pagano ME, Stout R, et al. Impact of obsessive-compulsive disorder on quality of life. Compr Psychiatry. 2006;47(4):270-5. doi: 10.1016/j.comppsych.2005.11.006. [PubMed: 16769301]. [PubMed Central: PMC2633465].
  6. Sepehrmanesh Z, Ghoreyshi FS, Assarian F, Moosavi GA, Etesam F; AhmadvandA, et al. [Prevalence of mental disorders in general population of Kashan city]. Iranian Journal of Epidemiology. 2010;6(2):16-24. Persian.
  7. Mohammadi MR, Ghanizadeh A, Rahgozar M, Noorbala AA, Davidian H, Afzali HM, et al. Prevalence of obsessive-compulsive disorder in Iran. BMC Psychiatry. 2004;4:2. doi: 10.1186/1471-244X-4-2. [PubMed: 15018627]. [PubMed Central: PMC362878].
  8. Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006;11(7):622-32. doi: 10.1038/sj.mp.4001823. [PubMed: 16585942].
  9. Pallanti S, Quercioli L. Treatment-refractory obsessive-compulsive disorder: methodological issues, operational definitions and therapeutic lines. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(3):400-12. doi: 10.1016/j.pnpbp.2005.11.028. [PubMed: 16503369].
  10. Dold M, Aigner M, Lanzenberger R, Kasper S. [Efficacy of antipsychotic augmentation therapy in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomised, placebo-controlled trials]. Fortschr Neurol Psychiatr. 2011;79(8):453-66. German. doi: 10.1055/s-0031-1273397. [PubMed: 21809258].
  11. Hollander E, Kwon JH, Stein DJ, Broatch J, Rowland CT, Himelein CA. Obsessive-compulsive and spectrum disorders: overview and quality of life issues. J Clin Psychiatry. 1996;57 Suppl 8:3-6. [PubMed: 8698678].
  12. Sadock BJ, Alcott Sadock V, Ruiz P. Kaplan and Sadock's comprehensive textbook of psychiatry. 9th ed. 2017.
  13. Afshar H, Roohafza H, Mohammad-Beigi H, Haghighi M, Jahangard L, Shokouh P, et al. N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2012;32(6):797-803. doi: 10.1097/JCP.0b013e318272677d. [PubMed: 23131885].
  14. Decloedt EH, Stein DJ. Current trends in drug treatment of obsessive-compulsive disorder. Neuropsychiatr Dis Treat. 2010;6:233-42. doi: 10.2147/ndt.s3149. [PubMed: 20520787]. [PubMed Central: PMC2877605].
  15. Carey PD, Lochner C, Kidd M, Van Ameringen M, Stein DJ, Denys D. Quetiapine augmentation of serotonin reuptake inhibitors in treatment-refractory obsessive-compulsive disorder: is response to treatment predictable? Int Clin Psychopharmacol. 2012;27(6):321-5. doi: 10.1097/YIC.0b013e3283576881. [PubMed: 22859064].
  16. Bloom FE, Morales M. The central 5-HT3 receptor in CNS disorders. Neurochem Res. 1998;23(5):653-9. doi: 10.1023/a:1022486705184. [PubMed: 9566603].
  17. Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A. 1988;85(14):5274-8. doi: 10.1073/pnas.85.14.5274. [PubMed: 2899326]. [PubMed Central: PMC281732].
  18. Pallanti S, Bernardi S, Antonini S, Singh N, Hollander E. Ondansetron augmentation in treatment-resistant obsessive-compulsive disorder: a preliminary, single-blind, prospective study. CNS Drugs. 2009;23(12):1047-55. doi: 10.2165/11530240-000000000-00000. [PubMed: 19958042].
  19. Pallanti S, Bernardi S, Antonini S, Singh N, Hollander E. Ondansetron augmentation in patients with obsessive-compulsive disorder who are inadequate responders to serotonin reuptake inhibitors: improvement with treatment and worsening following discontinuation. Eur Neuropsychopharmacol. 2014;24(3):375-80. doi: 10.1016/j.euroneuro.2013.12.003. [PubMed: 24406025].
  20. Soltani F, Sayyah M, Feizy F, Malayeri A, Siahpoosh A, Motlagh I. A double-blind, placebo-controlled pilot study of ondansetron for patients with obsessive-compulsive disorder. Hum Psychopharmacol. 2010;25(6):509-13. doi: 10.1002/hup.1145. [PubMed: 20737524].
  21. Heidari M, Zarei M, Hosseini SM, Taghvaei R, Maleki H, Tabrizi M, et al. Ondansetron or placebo in the augmentation of fluvoxamine response over 8 weeks in obsessive-compulsive disorder. Int Clin Psychopharmacol. 2014;29(6):344-50. doi: 10.1097/YIC.0000000000000043. [PubMed: 24850229].
  22. Hewlett WA, Schmid SP, Salomon RM. Pilot trial of ondansetron in the treatment of 8 patients with obsessive-compulsive disorder. J Clin Psychiatry. 2003;64(9):1025-30. doi: 10.4088/jcp.v64n0907. [PubMed: 14628977].
  23. Broocks A, Pigott TA, Hill JL, Stephanie C, Grady TA, L'Heureux F, et al. Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive–compulsive disorder (OCD): behavioral and biological results. Psychiatry Research. 1998;79(1):11-20. doi: 10.1016/s0165-1781(98)00029-8.
  24. Charney DS, Goodman WK, Price LH, Woods SW, Rasmussen SA, Heninger GR. Serotonin function in obsessive-compulsive disorder. A comparison of the effects of tryptophan and m-chlorophenylpiperazine in patients and healthy subjects. Arch Gen Psychiatry. 1988;45(2):177-85. doi: 10.1001/archpsyc.1988.01800260095012. [PubMed: 3337615].
  25. Urraca N, Camarena B, Gomez-Caudillo L, Esmer MC, Nicolini H. Mu opioid receptor gene as a candidate for the study of obsessive compulsive disorder with and without tics. Am J Med Genet B Neuropsychiatr Genet. 2004;127B(1):94-6. doi: 10.1002/ajmg.b.20170. [PubMed: 15108189].
  26. Ye JH, Ponnudurai R, Schaefer R. Ondansetron: a selective 5-HT(3) receptor antagonist and its applications in CNS-related disorders. CNS Drug Rev. 2001;7(2):199-213. doi: 10.1111/j.1527-3458.2001.tb00195.x. [PubMed: 11474424]. [PubMed Central: PMC6741689].
  27. Miyata K, Ito H, Yamano M, Hidaka K, Kamato T, Nishida A, et al. Comparison of the effects of trimebutine and YM114 (KAE-393), a novel 5-HT3 receptor antagonist, on stress-induced defecation. Eur J Pharmacol. 1993;250(2):303-10. doi: 10.1016/0014-2999(93)90395-x. [PubMed: 8112388].