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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Placebo Effect in Obsessive-Compulsive Disorder (OCD). Placebo Response and Placebo Responders in OCD: The Trend Over Time

Author(s): Georgios D. Kotzalidis*, Antonio Del Casale, Maurizio Simmaco, Lucia Pancheri, Roberto Brugnoli, Marco Paolini, Ida Gualtieri, Stefano Ferracuti, Valeria Savoja, Ilaria Cuomo, Lavinia De Chiara, Alessio Mosca, Gabriele Sani, Paolo Girardi, Maurizio Pompili, Chiara Rapinesi and on behalf of the Sapienza Group for the Study of the Placebo Effect in Psychiatric Disorders

Volume 17, Issue 8, 2019

Page: [741 - 774] Pages: 34

DOI: 10.2174/1570159X16666181026163922

Price: $65

Abstract

Background: Placebo response appears to be increasing in antidepressant, antipsychotic and various internal medicine trials. A similar trend has been reported for OCD during 1989-1999. Placebo response is generally considered as the extent to which placebo treatment is associated with core symptom improvement. In this analysis, we used Joinpoint regression to assess the time trend of both placebo response and placebo responder rates according to the year of publication with no time restriction in OCD drug trials.

Methods: We included drug and/or psychotherapy trials vs. placebo from PubMed, Embase, CINAHL, and PsycINFO retrieved through the search (placebo OR sham) AND (obsessive* OR OCD). We included studies through investigator consensus. We then performed on data of included studies log-linear joinpoint segmented regression models using a p<0.05 cutoff.

Results: We included 113 studies from 112 published papers. Placebo mean annual response rates in OCD studies significantly increased from 1991 to 2017 with an annual percent change (APC) of 0.66%, while placebo mean annual responder rates also significantly increased from 2010 to 2017, with an APC of 5.45%. Drug mean annual response rates in OCD studies significantly increased from 1987 to 2012 with an APC of 0.72%, while the corresponding responder rates did not show statistically significant APC changes between 1984 and 2017.

Conclusion: We observed a tendency for placebo to increase both measures of response in OCD clinical drug trials through the years that tend to approximate the responses shown by drugs. Changes in the type of study (moving from classical head to head comparisons to add-on studies in treatmentresistant populations) and countries involved in experimentation may partially account for some portion of these results. It appears that placebo effects are becoming more elusive and out of control.

Keywords: Obsessive-compulsive disorder, placebo response, placebo effect, publication year.

Graphical Abstract

[1]
Mavissakalian, M.R.; Jones, B.; Olson, S. Absence of placebo response in obsessive-compulsive disorder. J. Nerv. Ment. Dis., 1990, 178(4), 268-270. [http://dx.doi.org/10.1097/00005053-199004000-00010]. [PMID: 2319236].
[2]
Goodman, W.K.; Price, L.H.; Rasmussen, S.A.; Mazure, C.; Fleischmann, R.L.; Hill, C.L.; Heninger, G.R.; Charney, D.S. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch. Gen. Psychiatry, 1989, 46(11), 1006-1011. [http://dx.doi.org/10.1001/archpsyc.1989.01810110048007]. [PMID: 2684084].
[3]
Goodman, W.K.; Price, L.H.; Rasmussen, S.A.; Mazure, C.; Delgado, P.; Heninger, G.R.; Charney, D.S. The yale-brown obsessive compulsive scale. II. Validity. Arch. Gen. Psychiatry, 1989, 46(11), 1012-1016. [http://dx.doi.org/10.1001/archpsyc.1989.01810110054008]. [PMID: 2510699].
[4]
Guy, W. ECDEU Assessment Manual of Psychopharmacology — Revised (DHEW Publ No ADM 76-338). Rockville, MD, U.S;, Department of health, education, and welfare, public health service, alcohol, drug abuse, and mental health administration, NIMH psychopharmacology research branch, division of extramural research programs,. 1976, 218-222.
[5]
Walsh, B.T.; Seidman, S.N.; Sysko, R.; Gould, M. Placebo response in studies of major depression: variable, substantial, and growing. JAMA, 2002, 287(14), 1840-1847. [http://dx.doi.org/10.1001/jama.287.14.1840]. [PMID: 11939870].
[6]
Sysko, R.; Walsh, B.T. A systematic review of placebo response in studies of bipolar mania. J. Clin. Psychiatry, 2007, 68(8), 1213-1217. [http://dx.doi.org/10.4088/JCP.v68n0807]. [PMID: 17854245].
[7]
Vieta, E.; Cruz, N. Increasing rates of placebo response over time in mania studies. J. Clin. Psychiatry, 2008, 69(4), 681-682. [http://dx.doi.org/10.4088/JCP.v69n0423g]. [PMID: 18507494].
[8]
Ackerman, D.L.; Greenland, S. Multivariate meta-analysis of controlled drug studies for obsessive-compulsive disorder. J. Clin. Psychopharmacol., 2002, 22(3), 309-317. [http://dx.doi.org/10.1097/00004714-200206000-00012]. [PMID: 12006902].
[9]
Fineberg, N.A.; Hawley, C.J.; Gale, T.M. Are placebo-controlled trials still important for obsessive compulsive disorder? Prog. Neuropsychopharmacol. Biol. Psychiatry, 2006, 30(3), 413-422. [http://dx.doi.org/10.1016/j.pnpbp.2005.11.012]. [PMID: 16413647].
[10]
Kirsch, I.; Sapirstein, G. Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication. How Expectancies Shape Behavior; Kirsch, I., Ed.; American Psychological Association: Washington, DC, 1999, pp. 303-320. [http://dx.doi.org/10.1037/10332-012]
[11]
Kobak, K.A.; Greist, J.H.; Jefferson, J.W.; Katzelnick, D.J.; Henk, H.J. Behavioral versus pharmacological treatments of obsessive compulsive disorder: a meta-analysis. Psychopharmacology (Berl.), 1998, 136(3), 205-216. [http://dx.doi.org/10.1007/s002130050558]. [PMID: 9566805].
[12]
Montgomery, S.A. Clomipramine in obsessional neurosis: a placebo controlled trial. Pharm. Med., 1980, 1, 189-192.
[13]
Thorén, P.; Åsberg, M.; Cronholm, B.; Jörnestedt, L.; Träskman, L. Clomipramine treatment of obsessive-compulsive disorder. I. A controlled clinical trial. Arch. Gen. Psychiatry, 1980, 37(11), 1281-1285. [http://dx.doi.org/10.1001/archpsyc.1980.01780240079009]. [PMID: 7436690].
[14]
Mavissakalian, M.; Turner, S.M.; Michelson, L.; Jacob, R. Tricyclic antidepressants in obsessive-compulsive disorder: antiobsessional or antidepressant agents? II. Am. J. Psychiatry, 1985, 142(5), 572-576. [http://dx.doi.org/10.1176/ajp.142.5.572]. [PMID: 3885761].
[15]
Foa, E.B.; Steketee, G.; Kozak, M.J.; Dugger, D. Effects of imipramine on depression and obsessive-compulsive symptoms. Psychiatry Res., 1987, 21(2), 123-136. [http://dx.doi.org/10.1016/0165-1781(87)90070-9]. [PMID: 3615688].
[16]
Foa, E.B.; Steketee, G.; Kozak, M.J.; Dugger, D. Imipramine and placebo in the treatment of obsessive-compulsives: their effect on depression and on obsessional symptoms. Psychopharmacol. Bull., 1987, 23(1), 8-11. [PMID: 3602334].
[17]
Perse, T.L.; Greist, J.H.; Jefferson, J.W.; Rosenfeld, R.; Dar, R. Fluvoxamine treatment of obsessive-compulsive disorder. Am. J. Psychiatry, 1987, 144(12), 1543-1548. [http://dx.doi.org/10.1176/ajp.144.12.1543]. [PMID: 3120604].
[18]
Goodman, W.K.; Price, L.H.; Rasmussen, S.A.; Delgado, P.L.; Heninger, G.R.; Charney, D.S. Efficacy of fluvoxamine in obsessive-compulsive disorder. A double-blind comparison with placebo. Arch. Gen. Psychiatry, 1989, 46(1), 36-44. [http://dx.doi.org/10.1001/archpsyc.1989.01810010038006]. [PMID: 2491940].
[19]
Jenike, M.A.; Baer, L.; Summergrad, P.; Minichiello, W.E.; Holland, A.; Seymour, R. Sertraline in obsessive-compulsive disorder: a double-blind comparison with placebo. 1990, 147, 923-928. erratum, Jenike and Baer, 147, 1393.
[20]
Chouinard, G. Sertraline in the treatment of obsessive compulsive disorder: two double-blind, placebo-controlled studies. Int. Clin. Psychopharmacol., 1992, 7(Suppl. 2), 37-41. [http://dx.doi.org/10.1097/00004850-199210002-00007]. [PMID: 1484177].
[21]
Riddle, M.A.; Scahill, L.; King, R.A.; Hardin, M.T.; Anderson, G.M.; Ort, S.I.; Smith, J.C.; Leckman, J.F.; Cohen, D.J. Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder. J. Am. Acad. Child Adolesc. Psychiatry, 1992, 31(6), 1062-1069. [http://dx.doi.org/10.1097/00004583-199211000-00011]. [PMID: 1429406].
[22]
Montgomery, S.A.; McIntyre, A.; Osterheider, M.; Sarteschi, P.; Zitterl, W.; Zohar, J.; Birkett, M.; Wood, A.J. A double-blind, placebo-controlled study of fluoxetine in patients with DSM-III-R obsessive-compulsive disorder. Eur. Neuropsychopharmacol., 1993, 3(2), 143-152. [http://dx.doi.org/10.1016/0924-977X(93)90266-O]. [PMID: 8364350].
[23]
Tollefson, G.D.; Rampey, A.H., Jr; Potvin, J.H.; Jenike, M.A.; Rush, A.J.; Dominguez, R.A.; Koran, L.M.; Shear, M.K.; Goodman, W.; Genduso, L.A. A multicenter investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder Arch. Gen. Psychiatry, 1994, 51, 559-567. erratum 51, 864
[24]
Tollefson, G.D.; Birkett, M.; Koran, L.; Genduso, L. Continuation treatment of OCD: double-blind and open-label experience with fluoxetine. J. Clin. Psychiatry, 1994, 55(Suppl.), 69-76. [PMID: 7961535].
[25]
Turner, S.M.; Jacob, R.G.; Beidel, D.C.; Himmelhoch, J. Fluoxetine treatment of obsessive-compulsive disorder. J. Clin. Psychopharmacol., 1985, 5(4), 207-212. [http://dx.doi.org/10.1097/00004714-198508000-00003]. [PMID: 3894437].
[26]
Pfeffer, C.R.; Klerman, G.L.; Hurt, S.W.; Lesser, M.; Peskin, J.R.; Siefker, C.A. Suicidal children grow up: demographic and clinical risk factors for adolescent suicide attempts. J. Am. Acad. Child Adolesc. Psychiatry, 1991, 30(4), 609-616. [http://dx.doi.org/10.1097/00004583-199107000-00013]. [PMID: 1890095].
[27]
Flament, M.F.; Rapoport, J.L.; Berg, C.J.; Sceery, W.; Kilts, C.; Mellström, B.; Linnoila, M. Clomipramine treatment of childhood obsessive-compulsive disorder. A double-blind controlled study. Arch. Gen. Psychiatry, 1985, 42(10), 977-983. [http://dx.doi.org/10.1001/archpsyc.1985.01790330057007]. [PMID: 3899048].
[28]
Pato, M.T.; Zohar-Kadouch, R.; Zohar, J.; Murphy, D.L. Return of symptoms after discontinuation of clomipramine in patients with obsessive-compulsive disorder. Am. J. Psychiatry, 1988, 145(12), 1521-1525. [http://dx.doi.org/10.1176/ajp.145.12.1521]. [PMID: 3057923].
[29]
Jenike, M.A.; Baer, L.; Summergrad, P.; Weilburg, J.B.; Holland, A.; Seymour, R. Obsessive-compulsive disorder: a double-blind, placebo-controlled trial of clomipramine in 27 patients. Am. J. Psychiatry, 1989, 146(10), 1328-1330. [http://dx.doi.org/10.1176/ajp.146.10.1328]. [PMID: 2675643].
[30]
Greist, J.H.; Jefferson, J.W.; Rosenfeld, R.; Gutzmann, L.D.; March, J.S.; Barklage, N.E. Clomipramine and obsessive compulsive disorder: a placebo-controlled double-blind study of 32 patients. J. Clin. Psychiatry, 1990, 51(7), 292-297. [PMID: 2195006].
[31]
Jenike, M.A.; Hyman, S.; Baer, L.; Holland, A.; Minichiello, W.E.; Buttolph, L.; Summergrad, P.; Seymour, R.; Ricciardi, J. A controlled trial of fluvoxamine in obsessive-compulsive disorder: implications for a serotonergic theory. Am. J. Psychiatry, 1990, 147(9), 1209-1215. [http://dx.doi.org/10.1176/ajp.147.9.1209]. [PMID: 2143637].
[32]
Katz, R.J.; DeVeaugh-Geiss, J.; Landau, P. Clomipramine in obsessive-compulsive disorder. Biol. Psychiatry, 1990, 28(5), 401-414. [http://dx.doi.org/10.1016/0006-3223(90)90408-T]. [PMID: 2207219].
[33]
Mavissakalian, M.R.; Jones, B.; Olson, S.; Perel, J.M. Clomipramine in obsessive-compulsive disorder: clinical response and plasma levels. J. Clin. Psychopharmacol., 1990, 10(4), 261-268. [http://dx.doi.org/10.1097/00004714-199008000-00005]. [PMID: 2286699].
[34]
Montgomery, S.A.; Montgomery, D.B.; Fineberg, N. Early response with clomipramine in obsessive compulsive disorder--a placebo controlled study. Prog. Neuropsychopharmacol. Biol. Psychiatry, 1990, 14(5), 719-727. [http://dx.doi.org/10.1016/0278-5846(90)90042-F]. [PMID: 2293252].
[35]
McDougle, C.J.; Price, L.H.; Goodman, W.K.; Charney, D.S.; Heninger, G.R. A controlled trial of lithium augmentation in fluvoxamine-refractory obsessive-compulsive disorder: lack of efficacy. J. Clin. Psychopharmacol., 1991, 11(3), 175-184. [http://dx.doi.org/10.1097/00004714-199106000-00005]. [PMID: 1820757].
[36]
Clomipramine in the treatment of patients with obsessive-compulsive disorder. Arch. Gen. Psychiatry, 1991, 48(8), 730-738. [http://dx.doi.org/10.1001/archpsyc.1991.01810320054008]. [PMID: 1883256].
[37]
DeVeaugh-Geiss, J.; Moroz, G.; Biederman, J.; Cantwell, D.; Fontaine, R.; Greist, J.H.; Reichler, R.; Katz, R.; Landau, P. Clomipramine hydrochloride in childhood and adolescent obsessive-compulsive disorder--a multicenter trial. J. Am. Acad. Child Adolesc. Psychiatry, 1992, 31(1), 45-49. [http://dx.doi.org/10.1097/00004583-199201000-00008]. [PMID: 1537780].
[38]
Mallya, G.K.; White, K.; Waternaux, C.; Quay, S. Short- and long-term treatment with obsessive-compulsive disorder with fluvoxamine. Ann. Clin. Psychiatry, 1992, 4, 77-80. [http://dx.doi.org/10.3109/10401239209150443].
[39]
Pigott, T.A.; L’Heureux, F.; Rubenstein, C.S.; Bernstein, S.E.; Hill, J.L.; Murphy, D.L. A double-blind, placebo controlled study of trazodone in patients with obsessive-compulsive disorder. J. Clin. Psychopharmacol., 1992, 12(3), 156-162. [http://dx.doi.org/10.1097/00004714-199206000-00002]. [PMID: 1629380].
[40]
Stein, D.J.; Hollander, E.; Mullen, L.S. Comparison of clomipramine, alprazolam and placebo in the treatment of obsessive compulsive disorder. Hum. Psychopharmacol., 1992, 7, 389-395. [http://dx.doi.org/10.1002/hup.470070604].
[41]
Grady, T.A.; Pigott, T.A.; L’Heureux, F.; Hill, J.L.; Bernstein, S.E.; Murphy, D.L. Double-blind study of adjuvant buspirone for fluoxetine-treated patients with obsessive-compulsive disorder. Am. J. Psychiatry, 1993, 150(5), 819-821. [http://dx.doi.org/10.1176/ajp.150.5.819]. [PMID: 8480832].
[42]
Hoehn-Saric, R.; McLeod, D.R.; Zimmerli, W.D.; Hipsley, P.A. Symptoms and physiologic manifestations in obsessive compulsive patients before and after treatment with clomipramine. J. Clin. Psychiatry, 1993, 54(7), 272-276. [PMID: 8335655].
[43]
McDougle, C.J.; Goodman, W.K.; Leckman, J.F.; Holzer, J.C.; Barr, L.C.; McCance-Katz, E.; Heninger, G.R.; Price, L.H. Limited therapeutic effect of addition of buspirone in fluvoxamine-refractory obsessive-compulsive disorder. Am. J. Psychiatry, 1993, 150(4), 647-649. [http://dx.doi.org/10.1176/ajp.150.4.647]. [PMID: 8465885].
[44]
McDougle, C.J.; Goodman, W.K.; Leckman, J.F.; Lee, N.C.; Heninger, G.R.; Price, L.H. Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics. Arch. Gen. Psychiatry, 1994, 51(4), 302-308. [http://dx.doi.org/10.1001/archpsyc.1994.03950040046006]. [PMID: 8161290].
[45]
Greist, J.; Chouinard, G.; DuBoff, E.; Halaris, A.; Kim, S.W.; Koran, L.; Liebowitz, M.; Lydiard, R.B.; Rasmussen, S.; White, K.; Sikes, C. Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder. Arch. Gen. Psychiatry, 1995, 52(4), 289-295. [http://dx.doi.org/10.1001/archpsyc.1995.03950160039008]. [PMID: 7702445].
[46]
Fux, M.; Levine, J.; Aviv, A.; Belmaker, R.H. Inositol treatment of obsessive-compulsive disorder. Am. J. Psychiatry, 1996, 153(9), 1219-1221. [http://dx.doi.org/10.1176/ajp.153.9.1219]. [PMID: 8780431].
[47]
Goodman, W.K.; Kozak, M.J.; Liebowitz, M.; White, K.L. Treatment of obsessive-compulsive disorder with fluvoxamine: a multicentre, double-blind, placebo-controlled trial. Int. Clin. Psychopharmacol., 1996, 11(1), 21-29. [http://dx.doi.org/10.1097/00004850-199603000-00003]. [PMID: 8732310].
[48]
Nakajima, T.; Kudo, Y.; Yamashita, I.; Asai, M.; Kamijima, K.; Murasaki, M.; Yamaguchi, N.; Saito, M.; Yamawaki, S.; Nishizono, M.; Hishikawa, Y.; Machiyama, Y.; Yamauchi, T.; Moriya, N.; Toru, M.; Hirose, T.; Kojima, T.; Shimizu, M.; Tamura, A.; Endo, S.; Suzuki, J.; Takemasa, K.; Uno, M.; Hasegawa, K.; Kariya, T. Clinical usefulness of Fluvoxamine Maleate (SME3110), a selective serotonin reuptake inhibitor, in the treatment of obsessive compulsive disorder: A double blind, placebo-controlled study investigating the therapeutic dose range and the efficacy of SME3110. J. Clin. Therap. Med., 1996, 12(3), 409-437. [Rinshou Iyaku].
[49]
Zohar, J.; Judge, R. Paroxetine versus clomipramine in the treatment of obsessive-compulsive disorder. Br. J. Psychiatry, 1996, 169(4), 468-474. [http://dx.doi.org/10.1192/bjp.169.4.468]. [PMID: 8894198].
[50]
Jenike, M.A.; Baer, L.; Minichiello, W.E.; Rauch, S.L.; Buttolph, M.L. Placebo-controlled trial of fluoxetine and phenelzine for obsessive-compulsive disorder. Am. J. Psychiatry, 1997, 154(9), 1261-1264. [http://dx.doi.org/10.1176/ajp.154.9.1261]. [PMID: 9286186].
[51]
Lindsay, M.; Crino, R.; Andrews, G. Controlled trial of exposure and response prevention in obsessive-compulsive disorder. Br. J. Psychiatry, 1997, 171, 135-139. [http://dx.doi.org/10.1192/bjp.171.2.135]. [PMID: 9337948].
[52]
Ushijima, S.; Kamijima, K.; Asai, M.; Murasaki, M.; Nakajima, T.; Kudo, Y.; Tashiro, N.; Kurihara, M.; Miura, S. Clinical evaluation of sertraline hydrochloride, a selective serotonin reuptake inhibitor in the treatment of obsessive- compulsive disorder: A double blind placebo controlled trial. Jpn. J. Neuropsychopharmacol., (Nihon Shinkei Seishin Yakurigaku Zasshi or Nihon Shinkei Seishin Yakuri Gakkai),, 1997, 19(6), 603-623.
[53]
Fallon, B.A.; Liebowitz, M.R.; Campeas, R.; Schneier, F.R.; Marshall, R.; Davies, S.; Goetz, D.; Klein, D.F. Intravenous clomipramine for obsessive-compulsive disorder refractory to oral clomipramine: a placebo-controlled study. Arch. Gen. Psychiatry, 1998, 55(10), 918-924. [http://dx.doi.org/10.1001/archpsyc.55.10.918]. [PMID: 9783563].
[54]
Li, J.; Xiang, H.; Du, H. Clinical controlled study of paroxetine and clomipramine in treatment of obsessive- compulsive disorder. Zhonghua jing shen ke za zhi (Chinese Journal of Psychiatry), 1998, 31, 215-217 (李建勋,向虎,杜海英. 帕罗西汀与氯丙咪嗪治疗强迫症的临床对照研究. 中华精神科杂志. 编辑部邮箱 1998年 04期31, 215-217. (1998, (4), 23-25)). (erroneously referred to as: Jianxun L, Hu X, Haiying D. Clinical controlled study of paroxetine and clomipramine in treatment of obsessive- compulsive disorder. Chinese J. Psychiatry, 1998, 31, 215-217. [Chinese].
[55]
March, J.S.; Biederman, J.; Wolkow, R.; Safferman, A.; Mardekian, J.; Cook, E.H.; Cutler, N.R.; Dominguez, R.; Ferguson, J.; Muller, B.; Riesenberg, R.; Rosenthal, M.; Sallee, F.R.; Wagner, K.D.; Steiner, H. Sertraline in children and adolescents with obsessive-compulsive disorder: a multicenter randomized controlled trial J.A.M.A, , 1998, 280, 1752-1756. erratum 283, 1293
[56]
Kronig, M.H.; Apter, J.; Asnis, G.; Bystritsky, A.; Curtis, G.; Ferguson, J.; Landbloom, R.; Munjack, D.; Riesenberg, R.; Robinson, D.; Roy-Byrne, P.; Phillips, K.; Du Pont, I.J. Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder. J. Clin. Psychopharmacol., 1999, 19(2), 172-176. [http://dx.doi.org/10.1097/00004714-199904000-00013]. [PMID: 10211919].
[57]
Dannon, P.N.; Sasson, Y.; Hirschmann, S.; Iancu, I.; Grunhaus, L.J.; Zohar, J. Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial. Eur. Neuropsychopharmacol., 2000, 10(3), 165-169. [http://dx.doi.org/10.1016/S0924-977X(00)00065-1]. [PMID: 10793318].
[58]
McDougle, C.J.; Epperson, C.N.; Pelton, G.H.; Wasylink, S.; Price, L.H. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder. Arch. Gen. Psychiatry, 2000, 57(8), 794-801. [http://dx.doi.org/10.1001/archpsyc.57.8.794]. [PMID: 10920469].
[59]
Geller, D.A.; Hoog, S.L.; Heiligenstein, J.H.; Ricardi, R.K.; Tamura, R.; Kluszynski, S.; Jacobson, J.G. Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial. J. Am. Acad. Child Adolesc. Psychiatry, 2001, 40(7), 773-779. [http://dx.doi.org/10.1097/00004583-200107000-00011]. [PMID: 11437015].
[60]
Montgomery, S.A.; Kasper, S.; Stein, D.J.; Bang, H.K.; Lemming, O.M. 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(2), 75-86. [http://dx.doi.org/10.1097/00004850-200103000-00002]. [PMID: 11236072].
[61]
Riddle, M.A.; Reeve, E.A.; Yaryura-Tobias, J.A.; Yang, H.M.; Claghorn, J.L.; Gaffney, G.; Greist, J.H.; Holland, D.; McConville, B.J.; Pigott, T.; Walkup, J.T. Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial. J. Am. Acad. Child Adolesc. Psychiatry, 2001, 40(2), 222-229. [http://dx.doi.org/10.1097/00004583-200102000-00017]. [PMID: 11211371].
[62]
Romano, S.; Goodman, W.; Tamura, R.; Gonzales, J. Long-term treatment of obsessive-compulsive disorder after an acute response: a comparison of fluoxetine versus placebo. J. Clin. Psychopharmacol., 2001, 21(1), 46-52. [http://dx.doi.org/10.1097/00004714-200102000-00009]. [PMID: 11199947].
[63]
Atmaca, M.; Kuloglu, M.; Tezcan, E.; Gecici, O. Quetiapine augmentation in patients with treatment resistant obsessive-compulsive disorder: a single-blind, placebo-controlled study. Int. Clin. Psychopharmacol., 2002, 17(3), 115-119. [http://dx.doi.org/10.1097/00004850-200205000-00004]. [PMID: 11981352].
[64]
Greist, J.H.; Marks, I.M.; Baer, L.; Kobak, K.A.; Wenzel, K.W.; Hirsch, M.J.; Mantle, J.M.; Clary, C.M. Behavior therapy for obsessive-compulsive disorder guided by a computer or by a clinician compared with relaxation as a control. J. Clin. Psychiatry, 2002, 63(2), 138-145. [http://dx.doi.org/10.4088/JCP.v63n0209]. [PMID: 11874215].
[65]
Koran, L.M.; Hackett, E.; Rubin, A.; Wolkow, R.; Robinson, D. Efficacy of sertraline in the long-term treatment of obsessive-compulsive disorder. Am. J. Psychiatry, 2002, 159(1), 88-95. [http://dx.doi.org/10.1176/appi.ajp.159.1.88]. [PMID: 11772695].
[66]
Liebowitz, M.R.; Turner, S.M.; Piacentini, J.; Beidel, D.C.; Clarvit, S.R.; Davies, S.O.; Graae, F.; Jaffer, M.; Lin, S.H.; Sallee, F.R.; Schmidt, A.B.; Simpson, H.B. Fluoxetine in children and adolescents with OCD: a placebo-controlled trial. J. Am. Acad. Child Adolesc. Psychiatry, 2002, 41(12), 1431-1438. [http://dx.doi.org/10.1097/00004583-200212000-00014]. [PMID: 12447029].
[67]
Geller, D.A.; Biederman, J.; Stewart, S.E.; Mullin, B.; Farrell, C.; Wagner, K.D.; Emslie, G.; Carpenter, D. Impact of comorbidity on treatment response to paroxetine in pediatric obsessive-compulsive disorder: is the use of exclusion criteria empirically supported in randomized clinical trials? J. Child Adolesc. Psychopharmacol., 2003, 13(Suppl. 1), S19-S29. [http://dx.doi.org/10.1089/104454603322126313]. [PMID: 12880497].
[68]
Hollander, E.; Kaplan, A.; Stahl, S.M. A double-blind, placebo-controlled trial of clonazepam in obsessive-compulsive disorder. World J. Biol. Psychiatry, 2003, 4(1), 30-34. [http://dx.doi.org/10.3109/15622970309167908]. [PMID: 12582975].
[69]
Hollander, E.; Baldini Rossi, N.; Sood, E.; Pallanti, S. Risperidone augmentation in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. Int. J. Neuropsychopharmacol., 2003, 6(4), 397-401. [http://dx.doi.org/10.1017/S1461145703003730]. [PMID: 14604454].
[70]
Hollander, E.; Allen, A.; Steiner, M.; Wheadon, D.E.; Oakes, R.; Burnham, D.B. Acute and long-term treatment and prevention of relapse of obsessive-compulsive disorder with paroxetine. J. Clin. Psychiatry, 2003, 64(9), 1113-1121. [http://dx.doi.org/10.4088/JCP.v64n0919]. [PMID: 14628989].
[71]
Hollander, E.; Koran, L.M.; Goodman, W.K.; Greist, J.H.; Ninan, P.T.; Yang, H.; Li, D.; Barbato, L.M. A double-blind, placebo-controlled study of the efficacy and safety of controlled-release fluvoxamine in patients with obsessive-compulsive disorder. J. Clin. Psychiatry, 2003, 64(6), 640-647. [http://dx.doi.org/10.4088/JCP.v64n0604]. [PMID: 12823077].
[72]
Bystritsky, A.; Ackerman, D.L.; Rosen, R.M.; Vapnik, T.; Gorbis, E.; Maidment, K.M.; Saxena, S. Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder using adjunctive olanzapine: a placebo-controlled trial. J. Clin. Psychiatry, 2004, 65(4), 565-568. [http://dx.doi.org/10.4088/JCP.v65n0418]. [PMID: 15119922].
[73]
Denys, D.; de Geus, F.; van Megen, H.J.; Westenberg, H.G. A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors. J. Clin. Psychiatry, 2004, 65(8), 1040-1048. [http://dx.doi.org/10.4088/JCP.v65n0803]. [PMID: 15323587].
[74]
Fux, M.; Benjamin, J.; Nemets, B. A placebo-controlled cross-over trial of adjunctive EPA in OCD. J. Psychiatr. Res., 2004, 38(3), 323-325. [http://dx.doi.org/10.1016/S0022-3956(03)00077-3]. [PMID: 15003438].
[75]
Geller, D.A.; Wagner, K.D.; Emslie, G.; Murphy, T.; Carpenter, D.J.; Wetherhold, E.; Perera, P.; Machin, A.; Gardiner, C. Paroxetine treatment in children and adolescents with obsessive-compulsive disorder: a randomized, multicenter, double-blind, placebo-controlled trial. J. Am. Acad. Child Adolesc. Psychiatry, 2004, 43(11), 1387-1396. [http://dx.doi.org/10.1097/01.chi.0000138356.29099.f1]. [PMID: 15502598].
[76]
Kamijima, K.; Murasaki, M.; Asai, M.; Higuchi, T.; Nakajima, T.; Taga, C.; Matsunaga, H. Paroxetine in the treatment of obsessive-compulsive disorder: randomized, double-blind, placebo-controlled study in Japanese patients. Psychiatry Clin. Neurosci., 2004, 58(4), 427-433. [http://dx.doi.org/10.1111/j.1440-1819.2004.01278.x]. [PMID: 15298657].
[77]
Shapira, N.A.; Ward, H.E.; Mandoki, M.; Murphy, T.K.; Yang, M.C.; Blier, P.; Goodman, W.K. A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder. Biol. Psychiatry, 2004, 55(5), 553-555. [http://dx.doi.org/10.1016/j.biopsych.2003.11.010]. [PMID: 15023585].
[78]
Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. JAMA, 2004, 292(16), 1969-1976. [http://dx.doi.org/10.1001/jama.292.16.1969]. [PMID: 15507582].
[79]
Carey, P.D.; Vythilingum, B.; Seedat, S.; Muller, J.E.; van Ameringen, M.; Stein, D.J. Quetiapine augmentation of SRIs in treatment refractory obsessive-compulsive disorder: a double-blind, randomised, placebo-controlled study. [ISRCTN83050762] BMC Psychiatry, 2005, 5, 5. . [http://dx.doi.org/10.1186/1471-244X-5-5]. [PMID: 15667657].
[80]
Erzegovesi, S.; Guglielmo, E.; Siliprandi, F.; Bellodi, L. Low-dose risperidone augmentation of fluvoxamine treatment in obsessive-compulsive disorder: a double-blind, placebo-controlled study. Eur. Neuropsychopharmacol., 2005, 15(1), 69-74. [http://dx.doi.org/10.1016/j.euroneuro.2004.04.004]. [PMID: 15572275].
[81]
Fineberg, N.A.; Sivakumaran, T.; Roberts, A.; Gale, T. Adding quetiapine to SRI in treatment-resistant obsessive-compulsive disorder: a randomized controlled treatment study. Int. Clin. Psychopharmacol., 2005, 20(4), 223-226. [http://dx.doi.org/10.1097/00004850-200507000-00005]. [PMID: 15933483].
[82]
Foa, E.B.; Liebowitz, M.R.; Kozak, M.J.; Davies, S.; Campeas, R.; Franklin, M.E.; Huppert, J.D.; Kjernisted, K.; Rowan, V.; Schmidt, A.B.; Simpson, H.B.; Tu, X. Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder. Am. J. Psychiatry, 2005, 162(1), 151-161. [http://dx.doi.org/10.1176/appi.ajp.162.1.151]. [PMID: 15625214].
[83]
Kobak, K.A.; Taylor, L.V.; Bystritsky, A.; Kohlenberg, C.J.; Greist, J.H.; Tucker, P.; Warner, G.; Futterer, R.; Vapnik, T. St John’s wort versus placebo in obsessive-compulsive disorder: results from a double-blind study. Int. Clin. Psychopharmacol., 2005, 20(6), 299-304. [http://dx.doi.org/10.1097/00004850-200511000-00003]. [PMID: 16192837].
[84]
Koran, L.M.; Aboujaoude, E.; Bullock, K.D.; Franz, B.; Gamel, N.; Elliott, M. Double-blind treatment with oral morphine in treatment-resistant obsessive-compulsive disorder. J. Clin. Psychiatry, 2005, 66(3), 353-359. [http://dx.doi.org/10.4088/JCP.v66n0312]. [PMID: 15766302].
[85]
Li, X.; May, R.S.; Tolbert, L.C.; Jackson, W.T.; Flournoy, J.M.; Baxter, L.R. Risperidone and haloperidol augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder: a crossover study. J. Clin. Psychiatry, 2005, 66(6), 736-743. [http://dx.doi.org/10.4088/JCP.v66n0610]. [PMID: 15960567].
[86]
Nakatani, E.; Nakagawa, A.; Nakao, T.; Yoshizato, C.; Nabeyama, M.; Kudo, A.; Isomura, K.; Kato, N.; Yoshioka, K.; Kawamoto, M. A randomized controlled trial of Japanese patients with obsessive-compulsive disorder--effectiveness of behavior therapy and fluvoxamine. Psychother. Psychosom., 2005, 74(5), 269-276. [http://dx.doi.org/10.1159/000086317]. [PMID: 16088264].
[87]
Buchsbaum, M.S.; Hollander, E.; Pallanti, S.; Baldini Rossi, N.; Platholi, J.; Newmark, R.; Bloom, R.; Sood, E. Positron emission tomography imaging of risperidone augmentation in serotonin reuptake inhibitor-refractory patients. Neuropsychobiology, 2006, 53(3), 157-168. [http://dx.doi.org/10.1159/000093342]. [PMID: 16707915].
[88]
O’Connor, K.P.; Aardema, F.; Robillard, S.; Guay, S.; Pélissier, M.C.; Todorov, C.; Borgeat, F.; Leblanc, V.; Grenier, S.; Doucet, P. Cognitive behaviour therapy and medication in the treatment of obsessive-compulsive disorder. Acta Psychiatr. Scand., 2006, 113(5), 408-419. [http://dx.doi.org/10.1111/j.1600-0447.2006.00767.x]. [PMID: 16603032].
[89]
Fineberg, N.A.; Tonnoir, B.; Lemming, O.; Stein, D.J. Escitalopram prevents relapse of obsessive-compulsive disorder. Eur. Neuropsychopharmacol., 2007, 17(6-7), 430-439. [http://dx.doi.org/10.1016/j.euroneuro.2006.11.005]. [PMID: 17240120].
[90]
Stein, D.J.; Andersen, E.W.; 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(4), 701-711. [http://dx.doi.org/10.1185/030079907X178838]. [PMID: 17407626].
[91]
Amiaz, R.; Fostick, L.; Gershon, A.; Zohar, J. Naltrexone augmentation in OCD: a double-blind placebo-controlled cross-over study. Eur. Neuropsychopharmacol., 2008, 18(6), 455-461. [http://dx.doi.org/10.1016/j.euroneuro.2008.01.006]. [PMID: 18353618].
[92]
Kordon, A.; Wahl, K.; Koch, N.; Zurowski, B.; Anlauf, M.; Vielhaber, K.; Kahl, K.G.; Broocks, A.; Voderholzer, U.; Hohagen, F. Quetiapine addition to serotonin reuptake inhibitors in patients with severe obsessive-compulsive disorder: a double-blind, randomized, placebo-controlled study. J. Clin. Psychopharmacol., 2008, 28(5), 550-554. [http://dx.doi.org/10.1097/JCP.0b013e318185e735]. [PMID: 18794652].
[93]
Greenberg, W.M.; Benedict, M.M.; Doerfer, J.; Perrin, M.; Panek, L.; Cleveland, W.L.; Javitt, D.C. Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults. J. Psychiatr. Res., 2009, 43(6), 664-670. [http://dx.doi.org/10.1016/j.jpsychires.2008.10.007]. [PMID: 19046587].
[94]
Sayyah, M.; Boostani, H.; Pakseresht, S.; Malaieri, A. Efficacy of aqueous extract of Echium amoenum in treatment of obsessive-compulsive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2009, 33(8), 1513-1516. [http://dx.doi.org/10.1016/j.pnpbp.2009.08.021]. [PMID: 19737592].
[95]
Mowla, A.; Khajeian, A.M.; Sahraian, A.; Chohedri, A.H.; Kashkoli, F. Topiramate augmentation in resistant OCD: a double-blind placebo-controlled clinical trial. CNS Spectr., 2010, 15(11), 613-617. [http://dx.doi.org/10.1017/S1092852912000065]. [PMID: 24726048].
[96]
Storch, E.A.; Murphy, T.K.; Goodman, W.K.; Geffken, G.R.; Lewin, A.B.; Henin, A.; Micco, J.A.; Sprich, S.; Wilhelm, S.; Bengtson, M.; Geller, D.A. A preliminary study of D-cycloserine augmentation of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. Biol. Psychiatry, 2010, 68(11), 1073-1076. [http://dx.doi.org/10.1016/j.biopsych.2010.07.015]. [PMID: 20817153].
[97]
Sayyah, M.; Boostani, H.; Pakseresht, S.; Malayeri, A. A preliminary randomized double-blind clinical trial on the efficacy of celecoxib as an adjunct in the treatment of obsessive-compulsive disorder. Psychiatry Res., 2011, 189(3), 403-406. [http://dx.doi.org/10.1016/j.psychres.2011.01.019]. [PMID: 21329988].
[98]
Muscatello, M.R.; Bruno, A.; Pandolfo, G.; Micò, U.; Scimeca, G.; Romeo, V.M.; Santoro, V.; Settineri, S.; Spina, E.; Zoccali, R.A. Effect of aripiprazole augmentation of serotonin reuptake inhibitors or clomipramine in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. J. Clin. Psychopharmacol., 2011, 31(2), 174-179. [http://dx.doi.org/10.1097/JCP.0b013e31820e3db6]. [PMID: 21346614].
[99]
Berlin, H.A.; Koran, L.M.; Jenike, M.A.; Shapira, N.A.; Chaplin, W.; Pallanti, S.; Hollander, E. Double-blind, placebo-controlled trial of topiramate augmentation in treatment-resistant obsessive-compulsive disorder. J. Clin. Psychiatry, 2011, 72(5), 716-721. [http://dx.doi.org/10.4088/JCP.09m05266gre]. [PMID: 20816027].
[100]
Pakseresht, S.; Boostani, H.; Sayyah, M. Extract of valerian root (Valeriana officinalis L.) vs. placebo in treatment of obsessive-compulsive disorder: a randomized double-blind study. J. Complement. Integr. Med., 2011, 8(1), 32. [http://dx.doi.org/10.2202/1553-3840.1465]. [PMID: 22718671].
[101]
Sayyah, M.; Olapour, A.; Saeedabad, Ys.; Yazdan, P.R.; Malayeri, A. Evaluation of oral zinc sulfate effect on obsessive-compulsive disorder: a randomized placebo-controlled clinical trial. Nutrition, 2012, 28(9), 892-895. [http://dx.doi.org/10.1016/j.nut.2011.11.027]. [PMID: 22465904].
[102]
Sayyah, M.; Sayyah, M.; Boostani, H.; Ghaffari, S.M.; Hoseini, A. Effects of aripiprazole augmentation in treatment-resistant obsessive-compulsive disorder (a double blind clinical trial). Depress. Anxiety, 2012, 29(10), 850-854. [http://dx.doi.org/10.1002/da.21996]. [PMID: 22933237].
[103]
Afshar, H.; Roohafza, H.; Mohammad-Beigi, H.; Haghighi, M.; Jahangard, L.; Shokouh, P.; Sadeghi, M.; Hafezian, H. 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. [http://dx.doi.org/10.1097/JCP.0b013e318272677d]. [PMID: 23131885].
[104]
Bruno, A.; Micò, U.; Pandolfo, G.; Mallamace, D.; Abenavoli, E.; Di Nardo, F.; D’Arrigo, C.; Spina, E.; Zoccali, R.A.; Muscatello, M.R. Lamotrigine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. J. Psychopharmacol. (Oxford), 2012, 26(11), 1456-1462. [http://dx.doi.org/10.1177/0269881111431751]. [PMID: 22351381].
[105]
Askari, N.; Moin, M.; Sanati, M.; Tajdini, M.; Hosseini, S.M.; Modabbernia, A.; Najand, B.; Salimi, S.; Tabrizi, M.; Ashrafi, M.; Hajiaghaee, R.; Akhondzadeh, S. Granisetron adjunct to fluvoxamine for moderate to severe obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial. CNS Drugs, 2012, 26(10), 883-892. [http://dx.doi.org/10.2165/11635850-000000000-00000]. [PMID: 22873680].
[106]
Ghaleiha, A.; Entezari, N.; Modabbernia, A.; Najand, B.; Askari, N.; Tabrizi, M.; Ashrafi, M.; Hajiaghaee, R.; Akhondzadeh, S. Memantine add-on in moderate to severe obsessive-compulsive disorder: randomized double-blind placebo-controlled study. J. Psychiatr. Res., 2013, 47(2), 175-180. [http://dx.doi.org/10.1016/j.jpsychires.2012.09.015]. [PMID: 23063327].
[107]
Storch, E.A.; Bussing, R.; Small, B.J.; Geffken, G.R.; McNamara, J.P.; Rahman, O.; Lewin, A.B.; Garvan, C.S.; Goodman, W.K.; Murphy, T.K. Randomized, placebo-controlled trial of cognitive-behavioral therapy alone or combined with sertraline in the treatment of pediatric obsessive-compulsive disorder. Behav. Res. Ther., 2013, 51(12), 823-829. [http://dx.doi.org/10.1016/j.brat.2013.09.007]. [PMID: 24184429].
[108]
Haghighi, M.; Jahangard, L.; Mohammad-Beigi, H.; Bajoghli, H.; Hafezian, H.; Rahimi, A.; Afshar, H.; Holsboer-Trachsler, E.; Brand, S. 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(4), 633-640. [http://dx.doi.org/10.1007/s00213-013-3067-z]. [PMID: 23525525].
[109]
Storch, E.A.; Goddard, A.W.; Grant, J.E.; De Nadai, A.S.; Goodman, W.K.; Mutch, P.J.; Medlock, C.; Odlaug, B.; McDougle, C.J.; Murphy, T.K. Double-blind, placebo-controlled, pilot trial of paliperidone augmentation in serotonin reuptake inhibitor-resistant obsessive-compulsive disorder. J. Clin. Psychiatry, 2013, 74(6), e527-e532. [http://dx.doi.org/10.4088/JCP.12m08278]. [PMID: 23842022].
[110]
Rodriguez, C.I.; Kegeles, L.S.; Levinson, A.; Feng, T.; Marcus, S.M.; Vermes, D.; Flood, P.; Simpson, H.B. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology, 2013, 38(12), 2475-2483. [http://dx.doi.org/10.1038/npp.2013.150]. [PMID: 23783065].
[111]
Simpson, H.B.; Foa, E.B.; Liebowitz, M.R.; Huppert, J.D.; Cahill, S.; Maher, M.J.; McLean, C.P.; Bender, J., Jr; Marcus, S.M.; Williams, M.T.; Weaver, J.; Vermes, D.; Van Meter, P.E.; Rodriguez, C.I.; Powers, M.; Pinto, A.; Imms, P.; Hahn, C.G.; Campeas, R. Cognitive-behavioral therapy vs. risperidone for augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: a randomized clinical trial. JAMA Psychiatry, 2013, 70(11), 1190-1199. [http://dx.doi.org/10.1001/jamapsychiatry.2013.1932]. [PMID: 24026523].
[112]
Park, J.M.; Small, B.J.; Geller, D.A.; Murphy, T.K.; Lewin, A.B.; Storch, E.A. Does D-cycloserine augmentation of CBT improve therapeutic homework compliance for pediatric obsessive-compulsive disorder? J. Child Fam. Stud., 2014, 23(5), 863-871. [http://dx.doi.org/10.1007/s10826-013-9742-1]. [PMID: 24999301].
[113]
Grant, P.J.; Joseph, L.A.; Farmer, C.A.; Luckenbaugh, D.A.; Lougee, L.C.; Zarate, C.A., Jr; Swedo, S.E. 12-week, placebo-controlled trial of add-on riluzole in the treatment of childhood-onset obsessive-compulsive disorder. Neuropsychopharmacology, 2014, 39(6), 1453-1459. [http://dx.doi.org/10.1038/npp.2013.343]. [PMID: 24356715].
[114]
Mataix-Cols, D.; Turner, C.; Monzani, B.; Isomura, K.; Murphy, C.; Krebs, G.; Heyman, I. Cognitive-behavioural therapy with post-session D-cycloserine augmentation for paediatric obsessive-compulsive disorder: pilot randomised controlled trial. Br. J. Psychiatry, 2014, 204(1), 77-78. [http://dx.doi.org/10.1192/bjp.bp.113.126284]. [PMID: 24262813].
[115]
Afshar, H.; Akuchekian, S.; Mahaky, B.; Zarean, E. Topiramate augmentation in refractory obsessive-compulsive disorder: A randomized, double-blind, placebo-controlled trial. J. Res. Med. Sci., 2014, 19(10), 976-981. [PMID: 25538783].
[116]
Sarris, J.; Oliver, G.; Camfield, D.A.; Dean, O.M.; Dowling, N.; Smith, D.J.; Murphy, J.; Menon, R.; Berk, M.; Blair-West, S.; Ng, C.H. N-acetyl cysteine (NAC) in the treatment of obsessive-compulsive disorder: a 16-week, double-blind, randomised, placebo-controlled study. CNS Drugs, 2015, 29(9), 801-809. [http://dx.doi.org/10.1007/s40263-015-0272-9]. [PMID: 26374743].
[117]
Pittenger, C.; Bloch, M.H.; Wasylink, S.; Billingslea, E.; Simpson, R.; Jakubovski, E.; Kelmendi, B.; Sanacora, G.; Coric, V. Riluzole augmentation in treatment-refractory obsessive-compulsive disorder: a pilot randomized placebo-controlled trial. J. Clin. Psychiatry, 2015, 76(8), 1075-1084. [http://dx.doi.org/10.4088/JCP.14m09123]. [PMID: 26214725].
[118]
Jahanbakhsh, S.P.; Manteghi, A.A.; Emami, S.A.; Mahyari, S.; Gholampour, B.; Mohammadpour, A.H.; Sahebkar, A. Evaluation of the efficacy of Withania somnifera (Ashwagandha) root extract in patients with obsessive-compulsive disorder: A randomized double-blind placebo-controlled trial. Complement. Ther. Med., 2016, 27, 25-29. [http://dx.doi.org/10.1016/j.ctim.2016.03.018]. [PMID: 27515872].
[119]
Paydary, K.; Akamaloo, A.; Ahmadipour, A.; Pishgar, F.; Emamzadehfard, S.; Akhondzadeh, S. N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: randomized, double-blind, placebo-controlled trial. J. Clin. Pharm. Ther., 2016, 41(2), 214-219. [http://dx.doi.org/10.1111/jcpt.12370]. [PMID: 26931055].
[120]
Khalkhali, M.; Aram, S.; Zarrabi, H.; Kafie, M.; Heidarzadeh, A. Lamotrigine augmentation versus placebo in serotonin reuptake inhibitors-resistant obsessive-compulsive disorder: a randomized controlled trial. Iran. J. Psychiatry, 2016, 11(2), 104-114. [PMID: 27437007].
[121]
Rutrick, D.; Stein, D.J.; Subramanian, G.; Smith, B.; Fava, M.; Hasler, G.; Cha, J.H.; Gasparini, F.; Donchev, T.; Ocwieja, M.; Johns, D.; Gomez-Mancilla, B. Mavoglurant augmentation in OCD patients resistant to selective serotonin reuptake inhibitors: a proof-of-concept, randomized, placebo-controlled, phase 2 study. Adv. Ther., 2017, 34(2), 524-541. [http://dx.doi.org/10.1007/s12325-016-0468-5]. [PMID: 28044255].
[122]
Feng, B.; Zhang, Z.J.; Zhu, R.M.; Yuan, G.Z.; Luo, L.Y.; McAlonan, G.M.; Xu, F.Z.; Chen, J.; Liu, L.Y.; Lv, Y.Y.; Wong, H.K.; Zhang, Y.; Zhu, L.X. Transcutaneous electrical acupoint stimulation as an adjunct therapy for obsessive-compulsive disorder: A randomized controlled study. J. Psychiatr. Res., 2016, 80, 30-37. [http://dx.doi.org/10.1016/j.jpsychires.2016.05.015]. [PMID: 27281260].
[123]
de Leeuw, A.S.; van Megen, H.J.; Kahn, R.S.; Westenberg, H.G. d-cycloserine addition to exposure sessions in the treatment of patients with obsessive-compulsive disorder. Eur. Psychiatry, 2017, 40, 38-44. [http://dx.doi.org/10.1016/j.eurpsy.2016.06.011]. [PMID: 27837671].
[124]
Asnaani, A.; Kaczkurkin, A.N.; Alpert, E.; McLean, C.P.; Simpson, H.B.; Foa, E.B. The effect of treatment on quality of life and functioning in OCD. Compr. Psychiatry, 2017, 73, 7-14. [http://dx.doi.org/10.1016/j.comppsych.2016.10.004]. [PMID: 27838572].
[125]
Ahmadpanah, M.; Reihani, A.; Ghaleiha, A.; Soltanian, A.; Haghighi, M.; Jahangard, L.; Sadeghi Bahmani, D.; Holsboer-Trachsler, E.; Brand, S. Buprenorphine augmentation improved symptoms of OCD, compared to placebo - Results from a randomized, double-blind and placebo-controlled clinical trial. J. Psychiatr. Res., 2017, 94, 23-28. [http://dx.doi.org/10.1016/j.jpsychires.2017.06.004]. [PMID: 28647677].
[126]
Modarresi, A.; Sayyah, M.; Razooghi, S.; Eslami, K.; Javadi, M.; Kouti, L. Memantine augmentation improves symptoms in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder: a randomized controlled trial. Pharmacopsychiatry, 2017, 2018 51(6), 263-269. [http://dx.doi.org/10.1055/s-0043-120268] [PMID: 29100251]
[127]
Costa, D.L.C.; Diniz, J.B.; Requena, G.; Joaquim, M.A.; Pittenger, C.; Bloch, M.H.; Miguel, E.C.; Shavitt, R.G. Randomized, double-blind, placebo-controlled trial of N-acetylcysteine augmentation for treatment-resistant obsessive-compulsive disorder. J. Clin. Psychiatry, 2017, 78(7), e766-e773. [http://dx.doi.org/10.4088/JCP.16m11101]. [PMID: 28617566].
[128]
Arabzadeh, S.; Shahhossenie, M.; Mesgarpour, B.; Rezaei, F.; Shalbafan, M.R.; Ghiasi, Z.; Akhondzadeh, S. L-carnosine as an adjuvant to fluvoxamine in treatment of obsessive compulsive disorder: A randomized double-blind study. Hum. Psychopharmacol., 2017, 32(4) [http://dx.doi.org/10.1002/hup.2584]. [PMID: 28485008].
[129]
Alphs, L.; Benedetti, F.; Fleischhacker, W.W.; Kane, J.M. Placebo-related effects in clinical trials in schizophrenia: what is driving this phenomenon and what can be done to minimize it? Int. J. Neuropsychopharmacol., 2012, 15(7), 1003-1014. [http://dx.doi.org/10.1017/S1461145711001738]. [PMID: 22217384].
[130]
Khan, A.; Fahl, M.K.; Faucett, J.; Khan, S.S.; Brown, W.A. Has the rising placebo response impacted antidepressant clinical trial outcome? Data from the US Food and Drug Administration 1987-2013. World Psychiatry, 2017, 16(2), 181-192. [http://dx.doi.org/10.1002/wps.20421]. [PMID: 28498591].
[131]
Khan, A.; Fahl, M.K.; Schilling, J.; Brown, W.A. Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016. PLoS One, 2018, 13(2)e0193043 [http://dx.doi.org/10.1371/journal.pone.0193043]. [PMID: 29489874].
[132]
Rutherford, B.R.; Pott, E.; Tandler, J.M.; Wall, M.M.; Roose, S.P.; Lieberman, J.A. Placebo response in antipsychotic clinical trials: a meta-analysis. JAMA Psychiatry, 2014, 71(12), 1409-1421. [http://dx.doi.org/10.1001/jamapsychiatry.2014.1319]. [PMID: 25321611].
[133]
Sugarman, M.A.; Kirsch, I.; Huppert, J.D. Obsessive-compulsive disorder has a reduced placebo (and antidepressant) response compared to other anxiety disorders: A meta-analysis. J. Affect. Disord., 2017, 218, 217-226. [http://dx.doi.org/10.1016/j.jad.2017.04.068]. [PMID: 28477500].
[134]
Kasper, S.; Dold, M. Factors contributing to the increasing placebo response in antidepressant trials. World Psychiatry, 2015, 14(3), 304-306. [http://dx.doi.org/10.1002/wps.20245]. [PMID: 26407782].
[135]
Khin, N.A.; Chen, Y.F.; Yang, Y.; Yang, P.; Laughren, T.P. Exploratory analyses of efficacy data from schizophrenia trials in support of new drug applications submitted to the US Food and Drug Administration. J. Clin. Psychiatry, 2012, 73(6), 856-864. [http://dx.doi.org/10.4088/JCP.11r07539]. [PMID: 22687813].
[136]
Tuttle, A.H.; Tohyama, S.; Ramsay, T.; Kimmelman, J.; Schweinhardt, P.; Bennett, G.J.; Mogil, J.S. Increasing placebo responses over time in U.S. clinical trials of neuropathic pain. Pain, 2015, 156(12), 2616-2626. [http://dx.doi.org/10.1097/j.pain.0000000000000333]. [PMID: 26307858].
[137]
Mancini, M.; Wade, A.G.; Perugi, G.; Lenox-Smith, A.; Schacht, A. Impact of patient selection and study characteristics on signal detection in placebo-controlled trials with antidepressants. J. Psychiatr. Res., 2014, 51, 21-29. [http://dx.doi.org/10.1016/j.jpsychires.2014.01.001]. [PMID: 24462042].
[138]
Perugi, G.; Akiskal, H.S.; Gemignani, A.; Pfanner, C.; Presta, S.; Milanfranchi, A.; Lensi, P.; Ravagli, S.; Maremmani, I.; Cassano, G.B. Episodic course in obsessive-compulsive disorder. Eur. Arch. Psychiatry Clin. Neurosci., 1998, 248(5), 240-244. [http://dx.doi.org/10.1007/s004060050044]. [PMID: 9840370].
[139]
Lin, H.; Yeh, C.B.; Peterson, B.S.; Scahill, L.; Grantz, H.; Findley, D.B.; Katsovich, L.; Otka, J.; Lombroso, P.J.; King, R.A.; Leckman, J.F. Assessment of symptom exacerbations in a longitudinal study of children with Tourette’s syndrome or obsessive-compulsive disorder. J. Am. Acad. Child Adolesc. Psychiatry, 2002, 41(9), 1070-1077. [http://dx.doi.org/10.1097/00004583-200209000-00007]. [PMID: 12218428].
[140]
Hróbjartsson, A.; Gøtzsche, P.C. Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N. Engl. J. Med., 2001, 344(21), 1594-1602. [http://dx.doi.org/10.1056/NEJM200105243442106]. [PMID: 11372012].
[141]
Busch, A.B.; He, Y.; Zelevinsky, K.; O’Malley, A.J. Predicting Participation in Psychiatric Randomized Controlled Trials: Insights From the STEP-BD. Psychiatr. Serv., 2015, 66(8), 817-823. [http://dx.doi.org/10.1176/appi.ps.201300557]. [PMID: 25828873].
[142]
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th; (DSM-5®); Arlington, VA: American Psychiatric Publishing, Inc, 2013.
[143]
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, ; 4th; –Text Revision, (DSM-IV-TR™) Washington, DC: American Psychiatric Association, 2000.
[144]
Fountoulakis, K.N.; McIntyre, R.S.; Carvalho, A.F. From randomized controlled trials of antidepressant drugs to the meta-analytic synthesis of evidence: methodological aspects lead to discrepant findings. Curr. Neuropharmacol., 2015, 13(5), 605-615. [http://dx.doi.org/10.2174/1570159X13666150630174343]. [PMID: 26467410].
[145]
Kaptchuk, T.J.; Stason, W.B.; Davis, R.B.; Legedza, A.R.; Schnyer, R.N.; Kerr, C.E.; Stone, D.A.; Nam, B.H.; Kirsch, I.; Goldman, R.H. Sham device v inert pill: randomised controlled trial of two placebo treatments. BMJ, 2006, 332(7538), 391-397. [http://dx.doi.org/10.1136/bmj.38726.603310.55]. [PMID: 16452103].
[146]
Wartolowska, K.; Judge, A.; Hopewell, S.; Collins, G.S.; Dean, B.J.; Rombach, I.; Brindley, D.; Savulescu, J.; Beard, D.J.; Carr, A.J. Use of placebo controls in the evaluation of surgery: systematic review. BMJ, 2014, 348, g3253. [http://dx.doi.org/10.1136/bmj.g3253]. [PMID: 24850821].
[147]
Kaptchuk, T.J.; Goldman, P.; Stone, D.A.; Stason, W.B. Do medical devices have enhanced placebo effects? J. Clin. Epidemiol., 2000, 53(8), 786-792. [http://dx.doi.org/10.1016/S0895-4356(00)00206-7]. [PMID: 10942860].
[148]
Brunoni, A.R.; Lopes, M.; Kaptchuk, T.J.; Fregni, F. Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis. PLoS One, 2009, 4(3)e4824 [http://dx.doi.org/10.1371/journal.pone.0004824]. [PMID: 19293925].

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