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A Review of the Treatment for Refractory Obsessive-Compulsive Disorder: From Medicine to Deep Brain Stimulation

Published online by Cambridge University Press:  07 November 2014

Abstract

This article provides an overview of the etiology, epidemiology, and first-line treatment options for obsessive-compulsive disorder (OCD). The subject of treatment-resistant and treatment-refractory OCD is the discussed, including a definition of these often-debated terms, and the latest treatment options delineated. This includes a review of the latest research concerning the pharmacological agents that have been studied as monotherapy or augmenting agents for the treatment of OCD, the use of experimental medications and procedures, treatment with reversible, minimally invasive procedure, such as vagal nerve stimulation and transcranial magnetic stimulation, invasive but the potentially reversible deep brain stimulation, and irreversible lesioning with ablative psychosurgery. A discussion of the role of psychotherapy in the treatment of OCD is also included.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2004

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References

REFERENCES

1. Stein, DJ, Stone, MH. Essential Papers on Obsessive-Compulsive Disorders. New York, NY: New York University Press; 1997.Google Scholar
2. Karno, M, Goldin, JM, Sorenson, SB et al. , The epidemiology of obsessive compulsive disorder in five US communities. Arch Gen Psychiatry. 1988;45:10941099.CrossRefGoogle ScholarPubMed
3. Bebbington, PE. Epidemiology of obsessive-compulsive disorder. Br J Psychiatry. 1998;35(suppl):26.CrossRefGoogle Scholar
4. Eichstedt, JA, Arnold, SL. Childhood-onset obsessive-compulsive disorder: a tic-related subtype of OCD? Clin Psychol Rev. 2001;21:137157.CrossRefGoogle ScholarPubMed
5. Geller, PA, Klier, CM, Neugebauer, R. Anxiety disorders following miscarriage. J Clin Psychiatry. 2001;62:432438.CrossRefGoogle ScholarPubMed
6. Williams, KE, Koran, LM. Obsessive-compulsive disorder in pregnancy, the puerperium, and the premenstruum. J Clin Psychiatry. 1997;58:330334.CrossRefGoogle ScholarPubMed
7. Swedo, SE, Leonard, HL, Garvey, M et al. , Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998;155:264271.CrossRefGoogle ScholarPubMed
8. Skoog, G, Skoog, I. A 40-year follow-up of patients with obsessive-compulsive disorder. Arch Gen Psychiatry. 1999;56:121127.CrossRefGoogle ScholarPubMed
9. Hollander, E, Greenwald, S, Neville, D, Johnson, J, Homig, CD, Weissman, MM. Uncomplicated and comorbid obsessive-compulsive disorder in an epidemiologic sample. Depress Anxiety. 1997;4:111119.3.0.CO;2-J>CrossRefGoogle Scholar
10. Hollander, E. Obsessive-Compulsive Relaxed Disorders. Washington, DC: American Psychiatric Press; 1993.Google Scholar
11. Dupont, RL, Rice, DP, Shiraki, S et al. , Economic costs of obsessive-compulsive disorder. Med Interface. 1995;8:102109.Google ScholarPubMed
12. Newth, S, Rachman, S. The concealment of obsessions. Behav Res Ther. 2001;39:457464.CrossRefGoogle ScholarPubMed
13. Goodman, WK, Price, LH, Rasmussen, SA et al. , The Yale-Brown obsessive compulsive scale. I: development, use, and reliability. Arch Gen Psychiatry. 1989;46:10061011.CrossRefGoogle ScholarPubMed
14. Goodman, WK, Price, LH, Rasmussen, SA et al. , The Yale-Brown obsessive compulsive scale. II: validity. Arch Gen Psychiatry. 1989;46:10121016.CrossRefGoogle ScholarPubMed
15. Scahill, L, Riddle, MA, McSwiggin-Hardin, M et al. , Children's Yale-Brown bsessive compulsive scale: reliability and validity. J Am Acad Child Adolesc Psychiatry. 1997;36:844852.CrossRefGoogle ScholarPubMed
16. Stein, DJ, Hollander, E, and Cohen, L. Neuropsychiatry of obsessive-compulsive disorder. In: Hollander, E, Zohar, J, Marazziti, D, Olivier, B, eds. Current Insists in Obsessive-Compulsive Disorder. Chicester, UK: Wiley; 1994:167182.Google Scholar
17. Rauch, SL, Baxter, LR Jr. Neuroimaging in obsessive-compulsive disorder and related disorders. In: Jenicke, MA, Baer, L, Minichiello, WE, eds. Obsessive-Compulsive Disorders: Practical Management. 3rd ed. St Louis, Mo: Mosby; 1998:289317.Google Scholar
18. Rosenberg, DR, Keshavan, MS. Toward a neurodevelopmental model of obsessive-compulsive disorder. Biol Psychiatry. 1998;43:623640.CrossRefGoogle Scholar
19. Hugo, F, van Heerden, BB, Zungu-Dirwayi, N, Stein, DJ. Functional brain imaging in obsessive-compulsive disorder secondary to neurological lesions. Depress Anxiety. 1999;10:129136.3.0.CO;2-B>CrossRefGoogle ScholarPubMed
20. Zungu-Dirwayi, N, Hugo, F, van Heerden, BB, Stein, DJ. Are musical obsessions a temporal lobe phenomenon? J Neuropsychiatry Clin Neurosci. 1999;11:398400.CrossRefGoogle ScholarPubMed
21. Szeszko, PR, Robinson, D, Alvir, JMJ et al. , Orbital frontal and amygdala volume reductions in obsessive-compulsive disorder. Arch Gen Psychiatry. 1999;56:913–19.CrossRefGoogle ScholarPubMed
22. Baxter, LR, Schwartz, JM, Bergman, KS et al. , Caudate glucose metabolic rate changes with both drug and behavior therapy for OCD. Arch Gen Psychiatry. 1992;49:681689.CrossRefGoogle Scholar
23. Tot, S, Ozge, A, Comelekoglu, U et al. , Association of QEEG findings with clinical characteristics of OCD: evidence of left frontotemporal dysfunction. Can J Psychiatry. 2002;47:538545.CrossRefGoogle ScholarPubMed
24. Bergqvist, PB, Dong, J, Blier, P. Effect of atypical antipsychotic drugs on 5-HT2 receptors in the rat orbito-frontal cortex: an in vivo electrophysiological study. Psychopharmacology. 1999;143:8996.CrossRefGoogle ScholarPubMed
25. Koran, LM, Pallanti, S, Quercioli, L. Sumatriptan, 5-HT(1D) receptors and obsessive-compulsive disorder. Eur Neuropsychopharmacol. 2001;11:169172.CrossRefGoogle ScholarPubMed
26. Stem, L, Zohar, J, Cohen, R, Sasson, Y. Treatment of severe, drug resistant obsessive compulsive disorder with the 5-HT(1D) agonist sumatriptan. Eur Neuropsychopharmacol. 1998;8:325328.Google Scholar
27. Mundo, E, Richter, MA, Sam, F, Macciardi, F, Kennedy, JL. Is the 5-HT(1Dbeta) receptor gene implicated in the pathogenesis of obsessive-compulsive disorder? Am J Psychiatry. 2000:157:11601161.CrossRefGoogle ScholarPubMed
28. Stein, DJ, van Heerden, BB, Wessels, CJ et al. , Single photon emission computed tomography of the brain with tc-99m HMPA O during sumatriptan challenge in obsessive-compulsive disorder: investigating die functional role of the serotonin auto-receptor. Prog Neuropsychopharm Biol Psychiatry. 1999;23:10791099.CrossRefGoogle Scholar
29. El Mansari, M, 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
30. Goodman, WK, McDougle, CJ, Lawrence, LP. Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive-compulsive disorder. J Clin Psychiatry. 1990;51(suppl):3643.Google ScholarPubMed
31. Swedo, SE, Rapaport, JL, Cheslow, DL et al. , High prevalence of obsessive-compulsive symptoms in patients with Sydenham's chorea. Am J Psychiatry. 1989;146:246249.Google ScholarPubMed
32. Leonard, HL, Swedo, SE. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Int J Neuropsychopharmacol. 2001;4:191198.CrossRefGoogle ScholarPubMed
33. Eisen, JL, Leonard, HL, Swedo, SE et al. , The use of antibody D8/17 to identify B cells in adults with obsessive-compulsive disorder. Psychiatry Res. 2001;104:221225.CrossRefGoogle ScholarPubMed
34. Stein, DJ, Goodman, WK, Rauch, SL. The cognitive-affective neuroscience of obsessive-compulsive disorder. Curr Psychiatry Rep. 2000;2:341346.CrossRefGoogle ScholarPubMed
35. Perlmutter, SJ, Leitman, SF, Garvey, MA et al. , Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorder in childhood. Lancet. 1999;354:11531158.CrossRefGoogle ScholarPubMed
36. Goodman, WK, Ward, HE, Kablinger, AS, Murphy, TK. Biological approaches to treatment-resistant obsessive-compulsive disorder. In: Goodman, WK, Rudorfer, MV, and Maser, JD, eds. Obsessive-Compulsive Disorder: Contemporary Issues in Management. London, UK: Lawrence Erlbaum Associates; 2000:333369.Google Scholar
37. Grados, MA, Riddle, MA. Pharmacological treatment of childhood obsessive-compulsive disorder: from theory to practice. J Clin Child Psychol. 2001;30:6779.CrossRefGoogle ScholarPubMed
38. Dougherty, DD, Rauch, SL, Jenike, MA. Pharmacological treatments for obsessive compulsive disorder. In: Nathan, PE, Gorman, JM, eds. A Guide to Treatments That Work. 2nd ed. London, UK: Oxford University Press; 2002:387410.Google Scholar
39. Greist, J, Chouinard, G, DuBoff, E et al. , Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder. Arch Gen Psychiatry. 1995;52:289295.CrossRefGoogle ScholarPubMed
40. Tollefson, G, Birkett, M, Koran, L, Genduso, L. Continuation treatment of OCD: double-blind and open-label experience with fiuoxetine. J Clin Psychiatry. 1994;55:6978.Google Scholar
41. Wheadon, DE, Bushnell, WD, Steiner, M. A fixed-dose comparison of 20, 40, or 60 mg paroxetine to placebo in the treatment of OCD. Paper presented at: Annual Meeting of the American College of Neuropsychopharmacology; December 7-11, 1993; Honolulu, Hawaii.Google Scholar
42. Goodman, WK, Price, LH, Rasmussen, SA et al. , Efficacy of fluvoxamine in obsessive-compulsive disorder. A double-blind comparison of fluvoxamine and placebo. Arch Gen Psychiatry. 1989;46:3640.CrossRefGoogle Scholar
43. Geller, DA, Biederman, J, Stewart, SE et al. , Which SSR? A meta-analysis of pharmacotherapy in pediatric obsessive-compulsive disorder. Am J Psychiatry. 2003;160:19191928.CrossRefGoogle Scholar
44. March, JS, Frances, A, Carpenter, D, Kahn, D. Treatment of obsessive-compulsive disorder: The Expert Consensus Panel for obsessive-compulsive disorder. J Clin Psychiatry. 1997;58(suppl):172.Google Scholar
45. American Academy of Child and Adolescent Psychiatry. Practice parameters for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 1998;37(suppl):2745.CrossRefGoogle Scholar
46. Ballenger, JC. Treatment of anxiety disorders to temission. J Clin Psychiatry. 2001;62(suppl):59.Google Scholar
47. McDougle, CJ, Goodman, WK, Leckman, JF et al. , Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder: a double-blind, placebo-controlled study in patients with and without tics. Arch Gen Psychiatry. 1994;51:302308.CrossRefGoogle ScholarPubMed
48. Albert, U, Bergesio, C, Pessina, E et al. , Management of treatment resistant obsessive-compulsive disorder: algorithms for pharmacotherapy. Panminerva Med. 2002;44:8391.Google ScholarPubMed
49. Marek, GJ, Carpenter, LL, McDougle, CJ, Price, LH. Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders. Neuropsychopharmacology. 2003;28:402–41.CrossRefGoogle ScholarPubMed
50. McDougle, CJ, Epperson, CN, Pelton, GH et al. , A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder. Arch Gen Psychiatry. 2000;57:794802.CrossRefGoogle ScholarPubMed
51. Hollander, E, Ross, NB, Sood, E, Pallanti, S. Risperidone augmentation in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo controlled study. Int J Neuropsychopharmacol. 2003;6:397401.CrossRefGoogle ScholarPubMed
52. Arias, F, Soto, JA, Garcia, MJ et al. , Efficacy and tolerance of risperidone addition in serotonin reuptake inhibitors (SRI) treatment for refractory obsessive-compulsive disorder. Eur Neuropsychopharmacol. 2002;12(suppl 3):S341.CrossRefGoogle Scholar
53. D'Amico, G, Cedro, C, Muscatello, MR et al. , Olanzapine augmentation of paroxetine-refractory obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:619623.CrossRefGoogle ScholarPubMed
54. Crocq, MA, Leclercq, P, Guillon, MS, Bailey, PE. Open-label olanzapine in obsessive-compulsive disorder refractory to antidepressant treatment. Eur Psychiatry. 2002;17:296297.CrossRefGoogle ScholarPubMed
55. Bystritsky, A, Ackerman, DL, Rosen, RM et al. , Augmentation of SSRI response in refractory OCD using adjunct olanzapine: a placebo-controlled trial. APA Annual Meeting, New Research Abstracts; 2001; New Orleans, LA:171172.Google Scholar
56. Shapira, NA, Ward, HE, Mandoki, M et al. , Placebo-controlled trial of fluoxetine versus fiuoxetine plus olanzapine in obsessive-compulsive disorder. Paper presented at: Annual Meeting of the New Clinical Drug Evaluation Unit; May 29, 2003; Boca Raton, FL.Google Scholar
57. Denys, D, Van Megen, H, Westenberg, HGM. Quetiapine addition to serotonin reuptake inhibitor treatment in patients with treatment-refractory obsessive-compulsive disorder: an open-label study. J Clin Psychiatry. 2002;63:700702.CrossRefGoogle ScholarPubMed
58. Atmaca, M, Kuloglu, M, Tezcan, E, Gecici, O. Quetiapine augmentation in patients with treatment resistant obsessive-compulsive disorder: a single-blind, placebocontrolled study. Int Clin Psychophormacol. 2002;17:115119.CrossRefGoogle Scholar
59. McDougle, CJ, Barr, LC, Goodman, WK et al. , Lack of efficacy of clozapine monotherapy in refractory obsessive-compulsive disorder. Am J Psychiatry. 1995;152:18121814.Google ScholarPubMed
60. Lykouras, L, Alevizos, B, Michalopoulou, P, Rabavilas, A. Obsessive-compulsive symptoms induced by atypical antipsychotics: a review of the reported cases. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:333346.CrossRefGoogle ScholarPubMed
61. de Haan, L, Beuk, N, Hoogenboom, B et al. , Obsessive-compulsive symptoms during treatment with olanzapine and risperidone: a prospective study of 113 patients with recent-onset schizophrenia or related disorders. J Clin Psychiatry. 2002;63:104107.CrossRefGoogle ScholarPubMed
62. Jenike, MA, Baer, L, Minichiello, WE et al. , Placebo-controlled trial of fiuoxetine and phenelzine for obsessive-compulsive disorder. Am J Psychiatry. 1997;154:12611264.Google ScholarPubMed
63. Pigott, TA, 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
64. McDougle, CJ, Price, LH, Goodman, WK et al. , A controlled trial of lithium augmentation in fluvoxamine-refractory obsessive compulsive disorder: lack of efficacy. J Clin Psychopharmacol. 1991;11:175184.CrossRefGoogle ScholarPubMed
65. Pigott, TA, L'Heureux, F, Hill, JL et al. , A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder. J Clin Psychopharmocol. 1992;12:1118.Google ScholarPubMed
66. McDougle, CJ, Goodman, WK, Leckman, JF et al. , Limited therapeutic effect of addition of buspirone in fluvoxamine-refractory obsessive-compulsive disorder. Am J Psychiatry. 1993;150:647649.Google ScholarPubMed
67. Grady, TA, Pigott, TA, L'Heureux, F et al. , Double-blind study of adjuvant buspirone for fluoxetine-treated patients with obsessive-compulsive disorder. Am J Psychiatry. 1993;150:819821.Google ScholarPubMed
68. Pigott, TA, L'Heureux, F, Rubenstein, CS et al. , A double-blind, placebo-controlled study of trazodone in patients with obsessive-compulsive disorder. J Clin Psychopharmacol. 1992;12:156162.Google ScholarPubMed
69. Dannon, PN, Sasson, Y, Hirschmann, S et al. , Pindolol augmentation in treatment-resistant obsessive compulsive: double-blind placebo controlled trial. Eur Neuropsychopharmacol. 2000;10:165169.CrossRefGoogle ScholarPubMed
70. Koran, LM, Mueller, K, Maloney, A. Will pindolol augment the response to a serotonin reuptake inhibitor in obsessive-compulsive disorder? J Clin Psychopharmacol. 1996;16:253254.CrossRefGoogle ScholarPubMed
71. 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
72. Jenike, MA. Drug treatment of obsessive-compulsive disorder. In: Jenike, MA, Baer, L, Minichiello, WE, eds. Obsessive Compulsive Disorders: Theory and Management. 2nd ed. Chicago, IL: Year Book Medical; 1990:249282.Google Scholar
73. Pigott, TA, L'Heureux, FL, Rubenstein, CS. A controlled trial of clonazepam augmentation in OCD patients treated with clomipramine or fiuoxetine. New Research Abstract. 144, 145th Annual Meeting of the American Psychiatric Association, Washington, DC, 1992;82.Google Scholar
74. Hollander, E, DeCaria, CM, Schneier, FR et al. , Fenfluramine augmentation of serotonin reuptake blockade antiobsessional treatment. J Clin Psychiatry. 1990;51:119123.Google ScholarPubMed
75. Hollander, E, Friedberg, J, Wasserman, S et al. , Venlafaxine in treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry. 2003;64:546550.CrossRefGoogle ScholarPubMed
76. Albert, U, Aguglia, E, Maina, G, Bogetto, F. Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: a preliminary single-blind, 12-week, controlled study. J Clin Psychiatry. 2002;63:10041009.CrossRefGoogle ScholarPubMed
77. Denys, D, Van Der Wee, N, Van Megen, HJ, Westenberg, HG. A double-blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder. J Clin Psychopharmacol. 2003;23:568575.CrossRefGoogle ScholarPubMed
78. Deltito, JA. Valproate pretreatment for the difficult-to-treat patient with OCD [letter]. J Clin Psychiatry. 1994;55:500.Google ScholarPubMed
79. Joffe, RT, Swinson, RP. Carbamazepine in obsessive-compulsive disorder. Biol Psychiatry. 1987;45:122124.Google Scholar
80. Cora-Locatelli, G, Greenberg, BD, Martin, J, Murphy, DL. Gabapentin augmentation for fluoxetine-treated patients with obsessive-compulsive disorder [letter]. J Clin Psychiatry. 1998;59:480481.CrossRefGoogle ScholarPubMed
81. Sporn, J, Smith, M, Jersino, JM et al. , A double-blind, placebo-controlled trial of gabapentin augmentation of fluoxetine for treatment of obsessive-compulsive disorder (OCD) Poster presented at: New Clinical Drug Evaluation Unit Program May 28-31, 2001; Phoenix, Ariz.Google Scholar
82. Iwata, Y, Kotani, Y, Hoshino, R et al. , Carbamazepine augmentation of clomipramine in the treatment of refractory obsessive-compulsive disorder [letter]. J Clin Psychiatry. 2000;61:528529.CrossRefGoogle ScholarPubMed
83. McMeekin, H. Successful treatment of obsessive-compulsive disorder with oxcarbazepine: a case report. JSC Med Assoc. 2003;98:316320.Google Scholar
84. Ramesh, TC, Khanna, S. Lamotrigine augmentation of serotonin re-uptake inhibitors in obsessive-compulsive disorder [letter]. Aust N Z J Psychiatry. 2000;34:527528.Google Scholar
85. Fallon, BA, Liebowitz, MR, Campeas, R et al. , Intravenous clomipramine for obsessive-compulsive disorder refractory to oral clomipramine: a placebo-controlled study. Arch Gen Psychiatry. 1998;55:918924.CrossRefGoogle ScholarPubMed
86. Pallanti, S, Quercioli, L, Koran, LM. Citalopram intravenous infusion in resistant obsessive-compulsive disorder: an open trial. J Clin Psychiatry 2002;63:796801.CrossRefGoogle ScholarPubMed
87. 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
88. Fux, M, Levine, J, Aviv, A, Belmaker, RH. Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry. 1996;153:12191221.Google ScholarPubMed
89. Fux, M, Benjamin, J, Belmaker, RH. Inositol versus placebo augmentation of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: a double-blind cross-over study. Int J Neuropsychopharmacol. 1999;2:193195.CrossRefGoogle ScholarPubMed
90. Harvey, BH, Brink, CB, Seedat, S, Stein, DJ. Defining the neuromolecular action of myo-inositol: application to obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:2132.CrossRefGoogle ScholarPubMed
91. Shapira, NA, Keck, PE, Goldsmith, TD et al. , Open-label pilot study of tramadol hydrochloride in treatment-refractory obsessive-compulsive disorder. Depress Anxiety. 1997;6:170173.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
92. Koran, LM, Bullock, KD, Franz, BE et al. , Double-blind oral morphine in treatment-resistant OCD. Presented at: Annual Meeting of the American Psychiatric Association. May 17-22, 2003; San Francisco, Calif.Google Scholar
93. Tao, R, Auerbach, SR. Increased extracellular serotonin in rat brain after systemic or intraraphe administration of morphine. J Neurochem. 1994;63:517524.CrossRefGoogle ScholarPubMed
94. Spampinato, U. Serotonin agonists reduce dopamine synthesis in the striatum only when the impulse flow of nigro-striatal neurons is intact. Brain Res. 1985;328:8995.CrossRefGoogle Scholar
95. Koran, LM, Quirk, T, Lorberbaum, JP, Elliott, M. Mirtazapine treatment of obsessive-compulsive disorder [letter]. J Clin Psychopharmacol. 2001;21:537539.CrossRefGoogle ScholarPubMed
96. Koran, LM, Chuong, HW. Mirtazapine treatment for adult OCD. Poster presented at: Annual Meeting of the American Psychiatric Association. May 17-22, 2003; San Francisco, Calif.Google Scholar
97. Maina, G, Albert, U, and Bogetto, F. Relapses after discontinuation of drug associated with increased resistance to treatment in obsessive-compulsive disorder. Int J Neuropsychopharmacol. 2001;16:3338.CrossRefGoogle ScholarPubMed
98. Freud, S. Two case histores: little Hans and the rat man. In: Strachey, J, ed. The Standard Edition of the Complete Psychological Works of Sigmund Freud. Vol 10. London, UK: Hogarth Press; 1953.Google Scholar
99. Keijsers, G, Hoogduin, C, Shaap, C. Predictors of treatment outcome in the behavioural treatment of obsessive-compulsive disorder. Br J Psychiatry. 1994;165:781786.CrossRefGoogle ScholarPubMed
100. Marks, I. Behavior therapy for obsessive-compulsive disorder: a decade of progress. Can J Psychiatry. 1997;42:1021–27.CrossRefGoogle ScholarPubMed
101. Foa, EB, Kozak, MJ. Psychological treatment for obsessive-compulsive disorder. In: Mavissakalian, MR, Prien, RF, eds. Long-term Treatments of Anxiety Disorders. Washington, DC: American Psychiatric Press; 1996:285309.Google Scholar
102. Christensen, H, Hadzi-Pavlovic, D, Andrews, G, Mattick, R. Behavior therapy and tricyclic medication in the treatment of obsessive-compulsive disorder: a quantitative review. J Consult Clin Psychol. 1987:55:701711.CrossRefGoogle ScholarPubMed
103. Cox, BJ, Swinson, RP, Morrison, B, Lee, PS. Clomipramine, fluoxetine, and behavior therapy in the treatment of obsessive-compulsive disorder: a meta-analysis. J Behav Ther Exp Psychiatry. 1993;24:149153.CrossRefGoogle ScholarPubMed
104. van Balkom, AJ, van Oppen, P, Vermeulen, AW et al. , A meta-analysis on the treatment of obsessive-compulsive disorder: comparison of antidepressants, behavior, and cognitive therapy. Clin Psychol Rev. 1994;5:359381.CrossRefGoogle Scholar
105.Hembree, EA, Riggs, DS, Kozak, MJ et al. , Long-term efficacy of exposure and ritual prevention therapy and serotonergic medications for obsessive-compulsive disorder. CNS Spectr. 2003;8:363–371,381.CrossRefGoogle ScholarPubMed
106. Albert, U, Maina, G, Forner, F, Bogetto, F. Cognitive-behavioral therapy in obsessive-compulsive disorder patients partially unresponsive to SRIs [abstract]. Eur Neuropsychopharmacol 2003;13(suppl 4):S357–S358.CrossRefGoogle Scholar
107. James, IA, Blackburn, IM. Cognitive therapy with obsessive-compulsive disorder. Br J Psychiatry. 1995; 166:444450.CrossRefGoogle ScholarPubMed
108. Fals-Stewart, W, Marks, AP, Schafer, J. A comparison of behavioral group therapy and individual behavior therapy in treating obsessive-compulsive disorder. J Nerv Ment Dis. 1993;181:189193.CrossRefGoogle ScholarPubMed
109. van Noppen, BL, Pato, MT, Marsland, R, Rasmussen, SA. A time-limited behavioral group for treatment of obsessive-compulsive disorder. J Psychother Pract Res. 1998;7:272280.Google Scholar
110. Rauch, SL, Jenike, MA, Alpert, NM et al. , Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using 15-0 labeled CO2 and positron emission tomography. Arch Gen Psychiatry. 1994;1:6270.CrossRefGoogle Scholar
111. Saxena, S, Brody, AL, Schwartz, JM, Baxter, LR. Neuorimaging and frontal-subcortical circuitry in obsessive compulsive disorder. Br J Psychiatry. 1998;173(suppl 35):2638.CrossRefGoogle Scholar
112. Vogt, BA, Pandya, DN. Cingulate cortex of the rhesus monkey. II: Cortical afferents. J Comp Neurol. 1987;262:271289.CrossRefGoogle ScholarPubMed
113. Cavada, C, Company, T, Tejedor, J et al. , The anatomical connections of the macaque monkey orbitofrontal cortex. Cereb Cortex. 2000;10:220242.CrossRefGoogle ScholarPubMed
114. Kemp, JM, Powell, TPS. The cortico-striate projections in the monkey. Brain. 1970;93:525546.CrossRefGoogle ScholarPubMed
115. Martuza, RL, Chiocca, EA, Jenike, MA et al. , Stereotactic radiofrequency thermal cingulotomy for obsessive compulsive disorder. J Neuropsychiatry Clin Neurosci. 1990;2:331336.Google ScholarPubMed
116. Cosgrove, GR, Rauch, SL. Psychosurgery. Neurosurg Clin N Am. 1995;6:167176.CrossRefGoogle ScholarPubMed
117. Kelly, D, Richardson, A, Mitchell-Heggs, N. Stereotactic limbic leucotomy: neuro-physiological aspects and operative technique. Br J Psychiatry. 1973;123:133140.CrossRefGoogle Scholar
118. Rauch, SL, Markris, N, Cosgrove, GR et al. , A magnetic resonance imaging study of regional cortical volumes following sterotactic anterior cingulotomy. CNS Spectr. 2001;6:214222.CrossRefGoogle Scholar
119. Sachdev, P, Trollor, J, Walker, A et al. , Bilateral orbitomedial leuocotomy for obsessive-compulsive: a single-case study using positron emission tomography. Aust N ZJ Psychiatry. 2001;35:684690.CrossRefGoogle ScholarPubMed
120. Cosgrove, GR, Ballantine, HT Jr. Cingulotomy in psychosurgery. In: Goldenberg, PL, Tasker, RR, eds. Textbook of Sterotoctic and Functional Neurosurgery. New York, NYMcGraw-Hill; 1998:19651970.Google Scholar
121. Dougherty, DD, Baer, L, Cosgrove, GR et al. , Update on cingulotomy for intractable obsessive-compulsive disorder: prospective long-term follow-up of 44 patients. Am J Psychiatry. 2002;159:269275.CrossRefGoogle Scholar
122. Baer, L, Rauch, SL, Ballantine, HT Jr et al. , Cingulotomy for intractable obsessive-compulsive disorder. Prospective long-term follow-up of 18 patients. Arch Gen Psychiatry. 1995;52:384392.CrossRefGoogle ScholarPubMed
123. Marin, RS. Apathy: Concept, syndrome, neural mechanisms, and treatment. Semin Clin Neuropsychiatry. 1996;1:304314.Google ScholarPubMed
124. Athwal, BS, Berkley, KJ, Hussain, I et al. , Brain responses to changes in bladder volume and urge to void in healthy men. Brain. 2001;124:369377.CrossRefGoogle ScholarPubMed
125. Devinsky, O, Morrell, MJ, Vogt, BA. Contributions of the anterior cingulated cortex to behavior. Brain. 1995;118:279306.CrossRefGoogle Scholar
126. Ballantine, HT Jr. Neurosurgery for behavioral disorders. In: Wilkins, RH, Rengachary, SS, eds. Neurosurgery. New York, NY: Etsevier/North Holland Biomedical Press;1985:25272537.Google Scholar
127. Kim, CH, Chang, JW, Koo, MS et al. , Anterior cingulotomy for refractory obsessive-compulsive disorder. Acta Psychiarr Scand. 2003;107:283290.CrossRefGoogle ScholarPubMed
128. Spangler, WJ, Cosgrove, GR, Ballantine, HT et al. , Magnetic resonance image-guided stereotactic cingulotomy for intractable psychiatric disease. Neurosurgery. 1996;38:10711078.CrossRefGoogle ScholarPubMed
129. Jenike, MA, Baer, L, Ballantine, HT Jr et al. , Cingulotomy for refractory obsessive-compulsive disorder: A long-term follow-up of 33 patients. Arch Gen Psychiatry. 1991;48:548555.CrossRefGoogle ScholarPubMed
130. Rauch, SL, Dougherty, DD, Cosgrove, GR et al. , Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder. Biol Psychiatry. 2001;50:659667.CrossRefGoogle ScholarPubMed
131. Montoya, A, Weiss, AP, Price, BH et al. , Magnetic resonance imaging-guided stereotactic limbic leucotomy for treatment of intractable psychiatric disease. Neurosurgery. 2002;50:10431052.Google ScholarPubMed
132. Hay, P, Sachdev, P, Cumming, S et al. , Treatment of obsessive-compulsive disorder by psychosurgery. Acta Psychiatr Scand. 1993;87:197207.CrossRefGoogle ScholarPubMed
133. Kim, MC, Lee, TK, Choi, CR. Review of long-term results of stereotactic psychosurgery. Neurol Med Chir (Tokyo). 2002;42:365371.CrossRefGoogle ScholarPubMed
134. George, MS, Post, RM, Ketter, TA et al. , Neural mechanisms of mood disorders. Curr Rev Mood Anxiety Disord. 1997;1:7183.Google Scholar
135. Van Bockstaele, EJ, Peoples, J, Valentino, RJ. Anatomic basis for differential regulation of the rostrolateral peri-locus coeruleus region by limbic afferents. Biol Psychiatry. 1999;46:13521363.CrossRefGoogle ScholarPubMed
136. Malhi, GS, Sachdev, P. Novel physical treatments for the management of neuro-psychiatric disorders. J Psychosom Res. 2002;53:709719.CrossRefGoogle Scholar
137. Harden, CL, Pulver, MC, Ravdin, CL et al. , A pilot study of mood in epilepy patients treated with vagus nerve stimulation. Epilepsy Behav. 2002;1:9399.CrossRefGoogle Scholar
138. Jobe, PC, Dailey, JW, Wernicke, JF. A noradrenergic and serotonergic hypothesis of the linkage between epilepsy and affective disorders. Orit Rev Neurobiol. 1999;13:317356.CrossRefGoogle ScholarPubMed
139. Rush, AJ, George, MS, Sackeim, HA et al. , Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study. Biol Psychiatry. 2000;47:276286.CrossRefGoogle ScholarPubMed
140. Ward, H, Ninan, PT, Pollack, M et al. , Treatment-refractory obsessive-compulsive disorder: potential benefit of VNS therapy. Poster presented at: Annual Meeting of the Anxiety Disorders Association of America. March 27-30, 2003; Toronto, Canada.Google Scholar
141. George, MS, Lisanby, SH, Sackeim, HA. Transcranial magnetic stimulation: applications in psychiatry. Arch Gen Psychiatry. 1999;56:300311.CrossRefGoogle Scholar
142. Greenberg, BD, Rezai, AR. Mechanisms and the current state of deep brain stimulation in neuropsychiatry. CNS Spectr. 2003;8:522526.CrossRefGoogle ScholarPubMed
143. Nuttin, BJ, Gabriels, LA, Cosyns, PR et al. , Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery. 2003;52:12631274.CrossRefGoogle ScholarPubMed
144. Barker, AT, Jalinous, R, Freeston, IL. Non-invasive stimulation of the human motor cortex. Lancet. 1985;1:11061107.CrossRefGoogle ScholarPubMed
145. Greenberg, BD, George, MS, Dearing, J et al. , Effect of prefrontal repetitive transcranial magnetic stimulation (rTMS) in obsessive-compulsive disorder: a preliminary study. Am J Psychiatry. 1997;154:867869.Google ScholarPubMed
146. Alonso, P, Pujol, J, Cardoner, N et al. , Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: A double-blind, placebo-controlled study. Am J Psychiatry. 2001;158:11431145.CrossRefGoogle ScholarPubMed
147. Martin, JLR, Barbanoj, MJ, Clos, S. Transcranial magnetic stimulation (TMS) for the treatment of obsessive-compulsive disorder (OCD). Cochrane Database Syst Rev 2003;3:CD003387.Google Scholar
148. Wasserman, EM. Risk and safety of repetitive transcranial magnetic stimulation (report and suggested guidelines from the International Workshop in the Safety of Repetitive Trnascranial Magnetic Stimulation, June 5-7, 1996). Electroencephalogr Clin Neurophysiol. 1998;108:116.CrossRefGoogle Scholar
149. Wasserman, EM, Cohen, LG, Flitman, SS et al. , Seizures in healthy people with repeated “safe” trains of transcranial magnetic stimuli. Lancet. 1996;347:825826.CrossRefGoogle Scholar
150. Rudorfer, MV. Electroconvulsive therapy in treatment-refractory obsessive-compulsive disorder. In: Goodman, WK, Rudorfer, MV, Maser, JD, eds. Obsessive-Compulswe Disorder: Contemporary Issues in Management. London, UK: Lawrence Erlbaum Associates; 2000:431455.Google Scholar