Hostname: page-component-848d4c4894-hfldf Total loading time: 0 Render date: 2024-05-25T11:04:02.865Z Has data issue: false hasContentIssue false

Issues and Strategies in Treating Refractory Obsessive-Compulsive Disorder

Published online by Cambridge University Press:  07 November 2014


The World Health Organization has determined that obsessive-compulsive disorder (OCD) is the 10th leading medical cause of disability across the globe. Unfortunately, a substantial proportion of patients with OCD fail to respond to medication trials. In the pivotal double-blind, placebo-controlled trials that established the efficacy of clomipramine and the selective serotonin reuptake inhibitors (SSRIs), 40% to 60% of patients were nonresponders to a given drug. Moreover, patients who do not respond to their first medication trial may be less likely than treatment-naive patients to respond to subsequent trials. For example, only 33% of patients participating in double-blind trials who had failed trials of one or more serotonin reuptake inhibitors (SRIs) benefited from a subsequent trial of sertra-line, compared with 53% of those who were treatment naive (Rasmussen, Baer, Eisen, and Shera, unpublished data, 15th Annual Meeting, American Psychiatric Association, May 17-22, 1997).

At the Fourth International Obsessive-Compulsive Disorder Conference, held in February 2000 in St. Thomas, US Virgin Islands, an afternoon panel was devoted to considering issues and strategies related to treatment-refractory OCD. The panel presentations were divided into three groups: time to response and outcome after long-term followup; pharmacologic strategies for nonresponders; and new data concerning nonpharmacologic interventions.

Academic Supplement
Copyright © Cambridge University Press 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)



1.Murray, CL, Lopez, AD. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability From Diseases, Injuries, and Risk Factors in 1990 and Projected. Cambridge, Mass: Harvard University Press; 1996.Google Scholar
2.Greist, JH, Jefferson, JW, Kobak, KA, Katzelnick, DJ, Serline, RC. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. Arch Gen Psychiatry. 1995;52:5360.CrossRefGoogle ScholarPubMed
3.Guy, Y, ed. ECDEU Assessment Manual for Psychopharmacology. Publication ADM 76-338 Washington, DC: US Department of Health and Human Services; 1976:218222.Google Scholar
4.Koran, LM, Gelenberg, AJ, Kornstein, SK, et al.Sertraline versus imipramine to prevent relapse in chronic depression. J Affective Disord. Forthcoming, 2000.Google Scholar
5.Donovan, SJ, Quitkin, FM, Stewart, JS. Duration of antidepressant trials: clinical and research implications. J Clin Psychopharmacol. 1994;14:6466.CrossRefGoogle ScholarPubMed
6.Saxena, S, Brody, AL, Schwartz, JM, Baxter, LR. Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder. Br J Psychiatry. 1998;173(suppl 35):2638.CrossRefGoogle Scholar
7.Alexander, GE, DeLong, MR, Strick, PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci. 1986;9:357381.CrossRefGoogle ScholarPubMed
8.Baxter, LR, Saxena, S, Brody, AL, et al.Brain mediation of obsessive-compulsive disorder symptoms: evidence from functional brain imaging studies in the human and non-human primate. Sem Clin Neuropsychiatry. 1996;1:3247.Google Scholar
9.Zald, DH, Kim, SW. Anatomy and function of the orbital frontal cortex, I: anatomy, neurocircuitry, and obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 1996;8:125138.Google ScholarPubMed
10.Modell, JG, Mountz, JM, Curtis, GC, Greden, JF. Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 1989;1:2736.Google ScholarPubMed
11.Baxter, LR, Schwartz, JM, Bergman, KS, et al.Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry. 1992;49:681689.CrossRefGoogle ScholarPubMed
12.Graybiel, AM. Neurotransmitters and neuromodulators in the basal ganglia. TINS. 1990;13:244254.Google ScholarPubMed
13.Insel, TR. Toward a neuroanatomy of obsessive-compulsive disorder. Arch Gen Psychiatry. 1992;49:739744.CrossRefGoogle Scholar
14.Parent, A, Hazrati, L-N.Functional anatomy of the basal ganglia, I: the cortico-basal ganglia-thalamo-cortical loop. Brain Res Rev. 1995;20:91127.CrossRefGoogle ScholarPubMed
15.Lavoie, B, Parent, A. Immunohistochemical study of the serotoninergic innervation of the basal ganglia in the squirrel monkey. J Comp Neurol. 1990;299:116.CrossRefGoogle ScholarPubMed
16.Alexander, GE, Crutcher, MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. TINS. 1990;13:266271.Google ScholarPubMed
17.Gerfen, CR, Engber, TM, Mahan, LC, Susel, DL, Mansma, FJ Jr, Sibley, DA. Dl and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990;250:14291432.CrossRefGoogle Scholar
18.Mansari, ME, Bouchard, C, Blier, P. Alteration of serotonin release in the guinea pig orbito-frontal cortex by selective serotonin reuptake inhibitors. Neuropsychopharmacology. 1995;13:117127.CrossRefGoogle ScholarPubMed
19.Bergqvist, PB, Bouchard, C, Blier, P. Effect of long-term administration of antidepressant treatments on serotonin release in brain regions involved in obsessive-compulsive disorder. Biol Psychiatry. 1999;45: 164174.CrossRefGoogle ScholarPubMed
20.Moore, GJ, MacMaster, FP, Stewart, C, Rosenberg, DA. Case study: Glutamatergic changes with paroxetine therapy for pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 1998;37: 663667.CrossRefGoogle ScholarPubMed
21.Sizer, AR, Kilpatrick, GJ, & Roberts, MH. A post-synaptic depressant modulatory action of 5-hydroxytryptamine on excitatory amino acid responses in rat entorhinal cortex in vitro. Neuropharmacology 31(6):531–9, 1992.CrossRefGoogle ScholarPubMed
22.Sporn, J, Sachs, G. The anticonvulsant lamotrigine in treatment-resistant manic-depressive illness. J Clin Psychopharmacol. 1997;17:185189.CrossRefGoogle ScholarPubMed
23.Hall, H, Sedvall, G, Magnusson, O, Kopp, J, Halldin, C, Funde, L. Distribution of Dl- and D2-dopamine receptors, and dopamine and its metabolites in the human brain. Neuropsychopharmacology. 1994;11:245256.CrossRefGoogle Scholar
24.Warneke, L. A possible new treatment approach to obsessive-compulsive disorder. Can J Psychiatry. 1997;42:667668.CrossRefGoogle ScholarPubMed
25.Winsberg, ME, Cassic, KS, Koran, LM. Hoarding in obsessive-compulsive disorder: a report of 20 cases. Clin Psychiatry. 1999;60:591597.CrossRefGoogle ScholarPubMed
26.Ravizza, L, Barzega, G, Bellino, S, Bogetto, F, Maina, G. Therapeutic effect and safety of adjunctive risperidone in refractory obsessive-compulsive disorder. Psychopharmacol Bull. 1996;32:677682.Google ScholarPubMed
27.Pigott, T, Pato, MT, L'Heureux, F, et al.A controlled comparison of adjuvant lithium carbonate or thyroid hormone in clomipramine-treated patients with obsessive-compulsive disorder. J Clin Psychopharmacol. 1991;11:242248.CrossRefGoogle ScholarPubMed
28.McDougle, CJ, Price, LH, Goodman, WK, Charney, DS, Heninger, GR. A controlled trial of lithium augmentation in fluvoxamine-refractory obsessive-compulsive disorder: lack of efficacy. J Clin Psychopharmacol. 1991;11:175184.CrossRefGoogle ScholarPubMed
29.Pigott, T, L'Heureux, F, Hill, JL, Bihari, K, Bernstein, SE, Murphy, DL. A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder. J Clin Psychopharmacol. 1992;12:1118.CrossRefGoogle ScholarPubMed
30.Pallanti, S, Quercioli, L, Paiva, RS, Koran, LM. Citalopram for treatment-resistant obsessive-compulsive disorder. Eur Psychiatry. 1999;14:101106.CrossRefGoogle ScholarPubMed
31.Koran, LM, Sallee, FR, Pallanti, S. Rapid benefit of intravenous pulse loading of clomipramine in obsessive-compulsive disorder. Am J Psychiatry. 1997;154:396401.Google ScholarPubMed
32.Koran, LM, Pallanti, S, Paiva, RS, Quercioli, L. Pulse loading versus gradual dosing of intravenous clomipramine in obsessive-compulsive disorder. Eur Neuropsychopharmacol. 1998;8:121126.CrossRefGoogle ScholarPubMed
33.Koran, LM, Pallanti, S. Intravenous pulse-loaded clomipramine in body dysmorphic disorder: two case reports. CNS Spectrums. 1996;1:5457.Google Scholar
34.Frank, E, Kupfer, DJ, Siegel, LR. Alliance not compliance: a philosophy of outpatient care. J Clin Psychiatry. 1995;56(suppl 1):1116; discussion 16-17.Google Scholar
35.Marazziti, D, Gemignani, A, Dell'Osso, L. Trazodone aug-mentation in OCD: a case series report. CNS Spectrums. 1999;4(12):4849.CrossRefGoogle Scholar
36.Marazziti, D, Pallanti, S. Effectiveness of olanzapine treatment for severe obsessive-compulsive disorder [letter]. Am J Psychiatry. 1999;156:18341835.CrossRefGoogle ScholarPubMed
37.Weiss, EL, Potenza, MN, McDougle, CJ, Epperson, CN. Olanzapine addition in obsessive-compulsive disorder refractory to selective serotonin reuptake inhibitors: an open-label case series. J Clin Psychiatry. 1999;60:524527.CrossRefGoogle ScholarPubMed
38.Koran, LM, Ringold, AL, Elliott, MA. Olanzapine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry. 2000;61. In press.Google ScholarPubMed
39.Rauch, SL, O'Sullivan, RL, Jenike, MA. Open treatment of obsessive-compulsive disorder with venlafaxine: a series of ten cases [letter]. J Clin Psychopharmacol. 1996;16:8183.CrossRefGoogle ScholarPubMed
40.Cora-Locatelli, G, Greenberg, BD, Martin, JD, Murphy, DL. Rebound psychiatric and physical symptoms after gabapentin discontinuation [letter]. J Clin Psychiatry. 1998;59:131.CrossRefGoogle ScholarPubMed
41.Greenberg, BD, Ziemann, U, Harmon, A, Murphy, DL, Wassermann, EM. Decreased neuronal inhibition in cerebral cortex in obsessive-compulsive disorder on transcranial magnetic stimulation. Lancet. 1998;352:881882.CrossRefGoogle ScholarPubMed
42.Greenberg, BD, George, MS, Martin, JD, et al.Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study. Am J Psychiatry. 1997;154:867869.Google ScholarPubMed
43.Insel, TR, Pickar, D. Naloxone administration in obsessive-compulsive disorder: report of two cases. Am ] Psychiatry. 1983;140:12191220.Google ScholarPubMed
44.Shapira, NA, Keck, PE, Goldsmith, TD, McConville, BJ, Eis, M, McElroy, SL. Open-label pilot study of tramadol hydrochloride in treatment-refractory obsessive-compulsive disorder. Depression Anxiety. 1997;6:170173.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
45.Schlaepfer, TE, Strain, EC, Greenberg, BD, et al.Site of opioid action in the human brain: mu and kappa agonists' subjective and cerebral blood flow effects. Am J Psychiatry. 1998;155:470473.CrossRefGoogle ScholarPubMed
46.Blier, P, Bergeron, R. Sequential administration of augmentation strategies in treatment-resistant obsessive-compulsive disorder: preliminary findings. Int Clin Psychopharmacol. 1996;11:3744.CrossRefGoogle ScholarPubMed
47.Koran, LM, Mueller, K, Maloney, A. Will pindolol augment the response to a serotonin reuptake inhibitor in obsessive-compulsive disorder [letter]. J Clin Eur Neuropsychopharmacol. 1998;8:121126.CrossRefGoogle Scholar
48.Mundo, E, Guglielmo, E, Bellodi, L. Effect of adjuvant pindolol on the antiobsessional response to fluvoxamine: a double-blind, placebo-controlled study. Int Clin Psychopharmacol. 1998;13:219224.CrossRefGoogle ScholarPubMed
49.Kozak, M, Leibowitz, M, Foa, E. Cognitive behavior therapy and pharmacotherapy for OCD: the NIMH-sponsored collaborative study. In: WK, Goodman, Rudorfer, M, Maser, J, eds. Treatment Challenges in Obsessive Compulsive Disorder. Mahwah, NJ: Erlbaum; in press.Google Scholar
50.Cottraux, J, Mollard, E, Bouvard, M, et al.A controlled study of fluvoxamine and exposure in obsessive-compulsive disorder. Int Clin Psychopharmacol. 1990;5:1730.CrossRefGoogle ScholarPubMed
51.Foa, E, Kozak, M, Steketee, G, McCarthy, P. Treatment of depressive and obsessive-compulsive symptoms in OCD by imipramine and behavior therapy. Br J Clin Psychol. 1992;31:279292.CrossRefGoogle Scholar
52.Simpson, HB, Gorfinkle, KS, Liebowitz, MR. Cognitive-behavioral therapy as an adjunct to serotonin reuptake inhibitors in obsessive-compulsive disorder: an open trial. J Clin Psychiatry. 1999;60:584590.CrossRefGoogle ScholarPubMed
53.Von Balkom, A, de Haan, E, van Oppen, P, Spinhoven, P, Hoogduin, C, van Dyck, R. Cognitive-behavioral therapy versus the combination in the treatment of obsessive-compulsive disorder. J Nerv Ment Dis. In press.Google Scholar
54.Baer, L, Rauch, SL, Ballantine, HT, et al.Cingulotomy for intractable obsessive-compulsive disorder: prospective long-term follow-up of 18 patients. Arch Gen Psychiatry. 1995;52:384392.CrossRefGoogle ScholarPubMed
55.Tollefson, GD, Birkett, M, Koran, L, Genduso, L. Continuation treatment of OCD: double-blind and open-label experience with fluoxetine. J Clin Psychiatry. 1994;55(suppl 10):6976.Google ScholarPubMed
56.Koran, LM. Obsessive-Compulsive and Related Disorders in Adults: A Comprehensive Clinical Guide. Cambridge, England: Cambridge University Press; 1999: 6270.Google Scholar
57.Hermesh, H, Aizenberg, D, Munitz, H. Trazodone treatment in clomipramine-resistant obsessive-compulsive disorder. Clin Neuropharmacol. 1990;13:322328.CrossRefGoogle ScholarPubMed
58.Seedat, S, Stein, DJ. Inositol augmentation of serotonin reuptake inhibitors in treatment-refractory obsessive-compulsive disorder: an open trial. Int Clin Psychopharmacol. 1999;14:353356.CrossRefGoogle ScholarPubMed
59.Stern, L, Zohar, J, Cohen, R, Sasson, Y. Treatment of severe, drug resistant obsessive-compulsive disorder with the 5-HT1D agonist sumatriptan. Eur Neuropsychopharmacol. 1999;8:325328.CrossRefGoogle Scholar
60.Koran, LM, Quirk, T, Lorberbaum, JP, Elliott, MA. Mirtazapine treatment of obsessive-compulsive disorder. J Clin Psychopharmacol. In press.Google Scholar
61.Moreno, FA, Delgado, PL. Hallucinogen-induced relief of obsessions and compulsions [letter]. Am J Psychiatry. 1997;154:10371038.Google ScholarPubMed
62.Saxena, S, Wang, D, Bystritsky, A, Baxter, LR. Risperidone augmentation of SRI treatment for refractory obsessive-compulsive disorder. J Clin Psychiatry. 1996;57:303306.Google ScholarPubMed
63.Stein, DJ, Bouwer, C, Hawkridge, S, Emsley, RA. Risperidone augmentation of serotonin reuptake inhibitors in obsessive-compulsive and related disorders. J Clin Psychiatry. 1997;58:119122.CrossRefGoogle ScholarPubMed
64.McDougle, CJ, Goodman, WK, Price, LH, Delgado, PL, Krystal, JH, Charney, DS. Neuroleptic addition in fluvoxamine-refractory obsessive-compulsive disorder. Am J Psychiatry. 1990;147:652654.Google ScholarPubMed