Lamotrigine Augmentation versus Placebo in Serotonin Reuptake Inhibitors-Resistant Obsessive-Compulsive Disorder: A Randomized Controlled Trial
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Abstract
Objective: Serotonin reuptake inhibitors are frequently used in first-line treatments for patients with obsessive-compulsive disorder. Nevertheless, many of these patients do not respond well to initial therapy. The hypothesis of glutamatergic dysfunction in specific brain regions has been proposed in the pathophysiology of obsessive-compulsive disorder. This study was designed to evaluate the possible efficacy of lamotrigine, a glutamatergic agent in Serotonin reuptake inhibitors-resistant patients with obsessive-compulsive disorder.
Method: This study was a 12-week, double blind, randomized, placebo-controlled trial of adjunctive fixed-doses of lamotrigine (100 mg) to Serotonin reuptake inhibitors therapy in obsessive-compulsive disorder. Eligible subjects who had a total Y-BOCS of 21 or above were randomly assigned to receive adjunctive treatment with either lamotrigine (n = 26), or placebo (n = 27). Response to lamotrigine was defined as clinical improvement (>25% decrease in the total Y-BOCS score), which was administered at weeks 0, 8 and 12.
Results: At the endpoint (week 12), significant differences were observed in obsession, compulsion, and total Y-BOCS scores comparing lamotrigine to placebo (P = 0.01, 0.005 and 0.007 respectively). The mean reduction in obsession, compulsion and total scores in lamotrigine group was about 4.15, 4.50 and 8.73, respectively. Similarly, the mean reductions in the placebo group were 2.52, 2.56 and 5.07. Effect sizes for efficacy measures were calculated by Cohen’s d, and it was calculated as 0.54 for the total YBOCS.
Conclusion: Our findings provide evidence that this augmentation is well tolerated and may be an effective strategy for patients with refractory obsessive-compulsive disorder.
1. Subramaniam M, Abdin E, Vaingankar JA, Chong SA. Obsessive--compulsive disorder: prevalence, correlates, help-seeking and quality of life in a multiracial Asian population. Soc Psychiatry Psychiatr Epidemiol 2012; 47: 2035-2043.
2. Subramaniam M, Soh P, Vaingankar JA, Picco L, Chong SA. Quality of life in obsessive-compulsive disorder: impact of the disorder and of treatment. CNS Drugs 2013; 27: 367-383.
3. Seibell PJ, Hollander E. Management of obsessive-compulsive Disorder. F1000Prime Rep. 2014; 1: 6: 68-74.
4. Fornaro M. Switching from serotonin reuptake inhibitors to agomelatine in patients with refractory obsessive-compulsive disorder: a 3 month follow-up case series. Ann Gen Psychiatry 2011; 28: 10.5
5. Bruno A, Mico U, Pandolfo G, Mallamace D, Abenavoli E, Di Nardo F, et al. Lamotrigine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. J Psychopharmacol 2012; 26: 1456-1462.
6. Dold M, Aigner M, Lanzenberger R, Kasper S. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials. Int J Neuropsychopharmacol 2013; 16: 557-574.
7. Abudy A, Juven-Wetzler A, Zohar J. Pharmacological management of treatment-resistant obsessive-compulsive disorder. CNS Drugs 2011; 25: 585-596.
8. Bandelow B. The medical treatment of obsessive-compulsive disorder and anxiety. CNS Spectr 2008; 13: 37-46.
9. 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: 622-632.
10. Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, et al. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry 2005; 58: 424-428.
11. Naaijen J, Lythgoe DJ, Amiri H, Buitelaar JK, Glennon JC. Fronto-striatal glutamatergic compounds in compulsive and impulsive syndromes: a review of magnetic resonance spectroscopy studies. Neurosci Biobehav Rev 2015; 52: 74-88.
12. Wu K, Hanna GL, Rosenberg DR, Arnold PD. The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder. Pharmacol Biochem Behav 2012; 100: 726-735.
13. Bhattacharyya S, Chakraborty K. Glutamatergic dysfunction--newer targets for anti-obsessional drugs. Recent Pat CNS Drug Discov 2007; 2: 47-55.
14. Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx 2006; 3: 69-81.
15. Pittenger C, Bloch MH, Williams K. Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment. Pharmacol Ther 2011; 132: 314-332.
16. Goodman WK, Grice DE, Lapidus KA, Coffey BJ. Obsessive-compulsive disorder. Psychiatric Clinics of North America 2014; 37: 257-267.
17. Nakamae T. [Novel treatment strategies for refractory patients with obsessive-compulsive disorder]. Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica 2013; 115: 997-1003.
18. Grados MA, Specht MW, Sung HM, Fortune D. Glutamate drugs and pharmacogenetics of OCD: a pathway-based exploratory approach. Expert Opin Drug Discov 2013; 8: 1515-1527.
19. Fineberg NA, Brown A, Reghunandanan S, Pampaloni I. Evidence-basedpharmacotherapy of obsessive-compulsivedisorder.Int J Neuropsychopharmacol 2012; 15: 1173-1191.
20. Grant P, Lougee L, Hirschtritt M, Swedo SE. An open-label trial of riluzole, a glutamate antagonist, in children with treatment-resistant obsessive-compulsive disorder. J Child Adolesc Psychopharmacol 2007; 17: 761-767.
21. Grant PJ, Joseph LA, Farmer CA, Luckenbaugh DA, Lougee LC, Zarate CA, Jr., et al. 12-week, placebo-controlled trial of add-on riluzole in the treatment of childhood-onset obsessive-compulsive disorder. Neuropsychopharmacology 2014; 39: 1453-1459.
22. Bakhla AK, Verma V, Soren S, Sarkhel S , Chaudhury S. An open-label trial of memantine in treatment-resistant obsessive-compulsive disorder. Ind Psychiatry J 2013; 22: 149-152.
23. Hosenbocus S, Chahal R. Memantine: a review of possible uses in child and adolescent psychiatry. J Can Acad Child Adolesc Psychiatry 2013; 22: 166-171.
24. Haghighi M, Jahangard L, Mohammad-Beigi H, Bajoghli H, Hafezian H, Rahimi A, et al. In a double-blind, randomized and placebo-controlled trial, adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders (OCD). Psychopharmacology (Berl) 2013; 228: 633-640.
25. Ghaleiha A, Entezari N, Modabbernia A, Najand B, Askari N, et al. Memantine add-on in moderate to severe obsessive-compulsive disorder: randomized double-blind placebo-controlled study. J Psychiatr Res. 2013; 47: 175-180.
26. Stewart SE, Jenike EA, Hezel DM, Stack DE, Dodman NH, Shuster L, et al. A single-blinded case-control study of memantine in severe obsessive-compulsive disorder. J Clin Psychopharmacol 2010; 30: 34-39.
27. Egashira N, Shirakawa A, Abe M, Niki T, Mishima K, Iwasaki K, et al. N-acetyl-L-cysteine inhibits marble-burying behavior in mice. J Pharmacol Sci 2012; 119: 97-101.
28. Xia J, Du Y, Han J, Liu G , Wang X. D-cycloserine augmentation in behavioral therapy for obsessive-compulsive disorder: a meta-analysis. Drug Des Devel Ther 2015; 9: 2101-2117.
29. Chasson GS, Buhlmann U, Tolin DF, Rao SR, Reese HE and Rowley T, et al. Need for speed: evaluating slopes of OCD recovery in behavior therapy enhanced with d-cycloserine. Behav Res Ther 2010; 48: 675-679.
30. Berlin HA, Koran LM, Jenike MA, Shapira NA, Chaplin W, Pallanti S, et al. Double-blind, placebo-controlled trial of topiramate augmentation in treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2011; 72: 716-721.
31. Reid JG, Gitlin MJ, Altshuler LL. Lamotrigine in psychiatric disorders. J Clin Psychiatry. 2013; 74: 675-684.
32. Italiano D, Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age: an update. Clin Pharmacokinet 2013; 52: 627-645.
33. Kumar TC, Khanna S. Lamotrigine augmentation of serotonin re-uptake inhibitors in obsessive-compulsive disorder. Aust N Z J Psychiatry 2000; 34: 527-528.
34. Arrojo-Romero M, Tajes Alonso M , de Leon J. Lamotrigine augmentation of serotonin reuptake inhibitors in severe and long-term treatment-resistant obsessive-compulsive disorder. Case Rep Psychiatry 2013; 2013: 1245-1249.
35. Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, et al. The Yale-Brown Obsessive Compulsive Scale II. Validity Arch Gen Psychiatry 1989; 46:1006-1011.
36. Poyurovsky M, Glick I, Koran LM. Lamotrigine augmentation in schizophrenia and schizoaffective patients with obsessive-compulsive symptoms. J Psychopharmacol 2010; 24: 861-866.
37. Zavodnick AD, Ali R.Lamotrigine in the treatment of unipolar depression with and without comorbidities: a literature review. Psychiatr Q 2012; 83: 371-383.
38. Afshar H, Akuchekian SH, ahaky B, Zarean E. Topiramate augmentation in refractory obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial. J Res Med Sci2014; 19: 976–981.
39. Damien F, Ted K , Franklin M, Fabrizio B. Placebo Effects: Biological, Clinical and Ethical Advances. Lancet 2010; 375: 686-695.
40. Wang XQ, Xiong J, Xu WH, Yu SY, Huang XS, Zhang JT, et al. Risk of a lamotrigine-related skin rash: current meta-analysis and postmarketing cohort analysis. Seizure 2015; 25: 52-61.
41. Pallanti S, Grassi G. Pharmacologic treatment of obsessive-compulsive disorder comorbidity. Expert Opin Pharmacother 2014; 15: 2543-2552.
42. Woody E, Szechtman H. Motivation, time course, and heterogeneity in obsessive-compulsive disorder. Psychological Review 2005; 112: 658-661.
43. Watson HJ, Rees CS. Meta-analysis of randomized, controlled treatment trials for pediatric obsessive-compulsive disorder. J Child Psychol Psychiatry 2008; 49: 489-498.
44. Bandelow B. The medical treatment of obsessive-compulsive disorder and anxiety. CNS Spectr 2008; 13: 37-46.
45. Amerio A, Stubbs B, Odone A, Tonna M, Marchesi C , Ghaemi SN. The prevalence and predictors of comorbid bipolar disorder and obsessive-compulsive disorder: A systematic review and meta-analysis. J Affect Disord 2015; 186: 99-109.
46. Geddes JR, Calabrese JR, Goodwin GM. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry 2009; 194: 4-9.
47. Jeong JH, Lee JG, Kim MD, Sohn I, Shim SH, Wang HR, et al. Korean Medication Algorithm for Bipolar Disorder 2014: comparisons with other treatment guidelines. Neuropsychiatr Dis Treat 2015; 11: 1561-1571.
48. Wang HR, Woo YS, Bahk WM. Anticonvulsants to treat post-traumatic stress disorder. Hum Psychopharmacol 2014; 29: 427-433.
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| Issue | Vol 11 No 2 (2016) | |
| Section | Articles | |
| Keywords | ||
| Drug Augmentation Lamotrigine Obsessive-Compulsive Disorder Serotonin Reuptake Inhibitors Treatment-Resistant | ||
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