Abstract
We sought to determine differences in efficacy and tolerability between different doses of selective serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder (OCD) using meta-analysis. We identified 9 studies involving 2268 subjects that were randomized, double-blind placebo-controlled clinical trials that compared multiple, fixed-doses of selective serotonin reuptake inhibitors (SSRIs) to each other and to placebo in the treatment of adults with OCD. Change in Y-BOCS score, proportion of treatment responders, and dropouts (all-cause and due to side-effects) were determined for each included study. Weighted mean difference was used to examine mean change in Y-BOCS score. Pooled absolute risk difference was used to examine dichotomous outcomes. Meta-analysis was performed using a fixed effects model in RevMan 4.2.8. We found that compared with either low or medium doses, higher doses of SSRIs were associated with improved treatment efficacy, using either Y-BOCS score or proportion of treatment responders as an outcome. Dose of SSRIs was not associated with the number of all-cause dropouts. Higher doses of SSRIs were associated with significantly higher proportion of dropouts due to side-effects. These results suggests that higher doses of SSRIs are associated with greater efficacy in the treatment of OCD. This SSRI efficacy pattern stands in contrast to other psychiatric disorders like Major Depressive Disorder. This greater treatment efficacy is somewhat counterbalanced by the greater side-effect burden with higher doses of SSRIs. At present, there are insufficient data to generalize these findings to children or adolescents with OCD.
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References
Bloch MH, Landeros-Weisenberger A, Rosario MC, Pittenger C, Leckman JF . Meta-Analysis of the Symptom Structure of Obsessive-Compulsive Disorder. American Journal of Psychiatry 165: 1532–1542, in press.
Mataix-Cols D, Rosario-Campos MC, Leckman JF . A multidimensional model of obsessive-compulsive disorder. Am J Psychiatry 2005; 162: 228–238.
Murray C, Lopez A (eds) The global burden of disease : a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Harvard University Press: Cambridge, MA, 1996.
Bebbington PE . Epidemiology of obsessive-compulsive disorder. Br J Psychiatry Suppl 1998; 35: 2–6.
Ruscio AM, Stein DJ, Chiu WT, Kessler RC . The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry; published online 26 August 2008; doi:10.1038/mp.2008.94.
Treatment of obsessive-compulsive disorder. The Expert Consensus Panel for obsessive-compulsive disorder. J Clin Psychiatry 1997; 58 (Suppl 4): 2–72.
Soomro GM, Altman D, Rajagopal S, Oakley-Browne M . Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database Syst Rev 2008; (1): CD001765.
Pallanti S, Hollander E, Bienstock C, Koran L, Leckman J, Marazziti D et al. Treatment non-response in OCD: methodological issues and operational definitions. Int J Neuropsychopharmacol 2002; 5: 181–191.
American_Psychiatric_Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. American Psychiatric Association: Arlington, VA, 2007.
American_Psychiatric_Association. Practice Guideline for the Treatment of Patients with Major Depression. American Psychiatric Association: Arlington, VA, 2000.
Bollini P, Pampallona S, Tibaldi G, Kupelnick B, Munizza C . Effectiveness of antidepressants. Meta-analysis of dose-effect relationships in randomised clinical trials. Br J Psychiatry 1999; 174: 297–303.
Zitterl W, Meszaros K, Hornik K, Twaroch T, Dossenbach M, Zitterl-Eglseer K et al. Efficacy of fluoxetine in Austrian patients with obsessive-compulsive disorder. Wien Klin Wochenschr 1999; 111: 439–442.
Hollander E, Allen A, Steiner M, Wheadon DE, Oakes R, Burnham DB . Acute and long-term treatment and prevention of relapse of obsessive-compulsive disorder with paroxetine. J Clin Psychiatry 2003; 64: 1113–1121.
Nakajima T, Kudo Y, Yamashita I . Clinical usefulness of Fluvoxamine Maleate (SME3110), a selective serotonin reuptake inhibitor, in the treatment of obsessive compulsive disorder: A dopuble blind, placebo-controlled study investigating the therapeutic dose range and the efficacy of SME3110. Journal of clinical therapeutics & medicine 1996; 12: 409–437.
Ushijima S, Kamajima K, Asai M, Murasaki M, Nakajima T, Kudo Y et al. Clinical evaluation of sertraline hydrochloride, a selective serotonin reuptake inhibitor in the treatment of obsessive-compulsive disorder - A double-blind, placebo controlled trial. Japanese Journal of Neuropsychopharmacology 1997; 19: 603–623.
Montgomery SA, McIntyre A, Osterheider M, Sarteschi P, Zitterl W, Zohar J et al. A double-blind, placebo-controlled study of fluoxetine in patients with DSM-III-R obsessive-compulsive disorder. The Lilly European OCD Study Group. Eur Neuropsychopharmacol 1993; 3: 143–152.
Montgomery SA, Kasper S, Stein DJ, Bang Hedegaard K, Lemming OM . Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared with placebo in obsessive-compulsive disorder. Int Clin Psychopharmacol 2001; 16: 75–86.
Greist J, Chouinard G, DuBoff E, Halaris A, Kim SW, Koran L et al. Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder. Arch Gen Psychiatry 1995; 52: 289–295.
Tollefson GD, Rampey Jr AH . Potvin JH, Jenike MA, Rush AJ, kominguez RA et al. A multicenter investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder. Arch Gen Psychiatry 1994; 51: 559–567.
Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry 1989; 46: 1006–1011.
Stein DJ, Andersen EW, Tonnoir B, Fineberg N . Escitalopram in obsessive-compulsive disorder: a randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study. Curr Med Res Opin 2007; 23: 701–711.
Dominguez RA . Serotonergic antidepressants and their efficacy in obsessive compulsive disorder. J Clin Psychiatry 1992; 53 (Suppl): 56–59.
Ninan PT, Koran LM, Kiev A, Davidson JR, Rasmussen SA, Zajecka JM et al. High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial. J Clin Psychiatry 2006; 67: 15–22.
Acknowledgements
We wish to thank Fumiaki Imamura for his help with Japanese translation. The authors acknowledge the National Institute of Mental Health support of the Yale Child Study Center Research Training Program (MHB, JFL), K05MH076273 (JFL), the National Institutes of Health Loan Repayment Program (MHB), the Doris Duke Charitable Foundation (CP), the support of the Tourette's Syndrome Association Inc. (JFL, CP), the APIRE/Eli Lilly Psychiatric Research Fellowship (MHB), and the APA/NIMH PMRTP Program (ALW). Prior Presentation: None.
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Bloch, M., McGuire, J., Landeros-Weisenberger, A. et al. Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder. Mol Psychiatry 15, 850–855 (2010). https://doi.org/10.1038/mp.2009.50
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DOI: https://doi.org/10.1038/mp.2009.50
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