Skip to main content
SpringerLink
Log in

Treatment Resistance in Obsessive-Compulsive Disorder

  • Chapter
  • First Online:
Treatment Resistance in Psychiatry

Abstract

Obsessive-compulsive disorder (OCD) impacts 2–3% of the population and can be disabling when severe. First-line treatments for OCD include (a) pharmacotherapy with serotonin reuptake inhibitors (SRIs), (b) cognitive behavioral therapy consisting of exposure and ritual prevention, and (c) their combination. However, many patients do not respond to these treatments and are commonly referred to as “treatment-resistant.” This chapter will review the many factors that can contribute to treatment resistance in OCD, as well as current treatment options for these individuals.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Arlington; 2013.

    Google Scholar 

  2. Goodman Wayne K, Price Lawrence H, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, et al. Yale-Brown obsessive compulsive scale: development, use, and reliability. Arch Gen Psychiatry. 1989;46:1006–11.

    Article  Google Scholar 

  3. Pittenger C, Kelmendi B, Bloch M, Krystal JH, Coric V. Clinical treatment of obsessive compulsive disorder. Psychiatry. 2005;2:34–43.

    PubMed  PubMed Central  Google Scholar 

  4. Foa E, Yadin E, Lichner T. Exposure and response (ritual) prevention for obsessive-compulsive disorder: therapist guide (treatments that work). 2nd ed. New York: Oxford University Press; 2012.

    Book  Google Scholar 

  5. Simpson HB. Pharmacotherapy for obsessive-compulsive disorder in adults. Up to date. 2015.

    Google Scholar 

  6. Foa EB, Liebowitz MR, Kozak MJ, et al. Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder. Am J Psychiatry. 2005;162:151–61.

    Article  PubMed  Google Scholar 

  7. Simpson HB, Foa EB, Liebowitz MR, et al. Cognitive-behavioral therapy vs risperidone for augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder. JAMA Psychiat. 2013;70:1190.

    Article  CAS  Google Scholar 

  8. Simpson HB, Huppert JD, Petkova E, Foa EB, Liebowitz MR. Response versus remission in obsessive-compulsive disorder. J Clin Psychiatry. 2006;67:269–76.

    Article  CAS  PubMed  Google Scholar 

  9. Simpson HB, Foa EB, Liebowitz MR, Ledley R, Huppert JD, Cahill S, et al. A randomized, controlled trial of cognitive-behavioral therapy for augmenting pharmacotherapy in obsessive-compulsive disorder. Am J Psychiatry. 2008;165:621–30.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Gershkovich M, Wheaton M, Simpson H. Management of treatment-resistant obsessive-compulsive disorder. Curr Treat Options Psychiatry. 2017;4:357–70.

    Article  Google Scholar 

  11. Haverkampf J. Treatment-resistant OCD. J Psychiatry Psychother Commun. 2014;3:91–4.

    Google Scholar 

  12. Mataix-Cols D, Rauch SL, Manzo PA, Jenike MA, Baer L. Use of factor-analyzed symptom dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive-compulsive disorder. Am J Psychiatry. 1999;156:1409–16.

    CAS  PubMed  Google Scholar 

  13. Farris SG. NIH Public Access. 2014;74:685–90.

    Google Scholar 

  14. Soomro GM, Altman DG, Rajagopal S, Oakley Browne M. Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database Syst Rev. 2008; https://doi.org/10.1002/14651858.CD001765.pub3.

  15. R a H, Saxena S, Rauch SL, Hoehn-Saric R, Taber KH. Predicting treatment response in obsessive-compulsive disorder. J Neuropsychiatr Clin Neurosci. 2002;14:249–53.

    Article  Google Scholar 

  16. Blair Simpson H. Pharmacotherapy for obsessive-compulsive disorder in adults. Uptodate. 2015.

    Google Scholar 

  17. Koran LM, Hollander E, Nestadt G, Simpson HB. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;64:5–53.

    Google Scholar 

  18. Bloch M, McGuire J, Landeros-Weisenberger A, Leckman JF, Pittenger C. Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder. Mol Psychiatry. 2010;15:850–5.

    Article  CAS  PubMed  Google Scholar 

  19. Tukel R, Bozkurt O, Polat A, Genc A, Atli H. Clinical predictors of response to pharmacotherapy with selective serotonin reuptake inhibitors in obsessive-compulsive disorder. Psychiatry Clin Neurosci. 2006;60:404–9.

    CAS  PubMed  Google Scholar 

  20. Stein D, Montgomery S, Kasper S, Tanghoi P. Predictors of response to pharmacotherapy with citalopram in obsessive-compulsive disorder. Int Clin Psychopharmacol. 2001;16:357–61.

    Article  CAS  PubMed  Google Scholar 

  21. Miguel EC, Shavitt RG, Ferrão YA, Brotto SA, Diniz JB. How to treat OCD in patients with Tourette syndrome. J Psychosom Res. 2003;55:49–57.

    Article  PubMed  Google Scholar 

  22. March JS, Franklin ME, Leonard H, Garcia A, Moore P, Freeman J, et al. Tics moderate treatment outcome with sertraline but not cognitive-behavior therapy in pediatric obsessive-compulsive disorder. Biol Psychiatry. 2007;61:344–7.

    Article  PubMed  Google Scholar 

  23. Geller D, Biederman J, Stewart S, Mullin B, Farrell C, Wagner K, et al. 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:S19–29.

    Article  PubMed  Google Scholar 

  24. Arumugham SS, Reddy JY. Augmentation strategies in obsessive-compulsive disorder. Expert Rev Neurother. 2013;13:187–203.

    Article  CAS  PubMed  Google Scholar 

  25. Kellner M. Drug treatment of obsessive-compulsive disorder. Dialogues Clin Neurosci. 2010;12:187–97.

    PubMed  PubMed Central  Google Scholar 

  26. Shetti C, Reddy Y, Kandavel T, Kashyap K, Singisetti S, Hiremath A, et al. Clinical predictors of drug nonresponse in obsessive-compulsive disorder. J Clin Psychiatry. 2005;66:1517–23.

    Article  PubMed  Google Scholar 

  27. Ravizza L, Barzega G, Bellino S, Bogetto F, Maina G. Predictors of drug treatment response in obsessive-compulsive disorder. J Clin Psychiatry. 1995;56:368–73.

    CAS  PubMed  Google Scholar 

  28. Erzegovesi S, Cavallini M, Cavallini M, Diaferia G, Locatelli M, Bellodi L. Clinical predictors of drug response in obsessive-compulsive disorder. J Clin Psychiatry. 2001;21:488–92.

    CAS  Google Scholar 

  29. Rosario-Campos M, Leckman J, Mercadante M, Shavitt R, Prado H, Sada P, et al. Adults with early-onset obsessive-compulsive disorder. Am J Psychiatry. 2001;158:1899–903.

    Article  CAS  PubMed  Google Scholar 

  30. Fenske JN, Petersen K. Obsessive-compulsive disorder: diagnosis and Management. Am Fam Physician. 2015;92(10):896–903.

    PubMed  Google Scholar 

  31. Koran LM, Simpson HB. Guideline watch (March 2013): practice guideline for the treatment of patients with obsessive-compulsive disorder. Arlington: American Psychiatric Association; 2013.

    Google Scholar 

  32. Carrasco J, Hollander E, Schneier F, Leibowitz M. Treatment outcome of obsessive compulsive disorder with comorbid social phobia. J Clin Psychiatry. 1992;53:387–91.

    CAS  PubMed  Google Scholar 

  33. Shavitt RG, Valério C, Fossaluza V, Da Silva EM, Cordeiro Q, Diniz JB, et al. The impact of trauma and post-traumatic stress disorder on the treatment response of patients with obsessive-compulsive disorder. Eur Arch Psychiatry Clin Neurosci. 2010;260:91–9.

    Article  PubMed  Google Scholar 

  34. Fontenelle LF, Cocchi L, et al. Towards a post-traumatic subtype of obsessive–compulsive disorder. J Anxiety Disord. 2012;26:377–83.

    Article  PubMed  Google Scholar 

  35. Kelly K, Posternak M, Alpert JE. Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues Clin Neurosci. 2008;10:409–18.

    PubMed  PubMed Central  Google Scholar 

  36. Pallanti S, Grassi G, Sarrecchia ED, Cantisani A, Pellegrini M. Obsessive-compulsive disorder comorbidity: clinical assessment and therapeutic implications. Front Psychol. 2011;2:1–11.

    Google Scholar 

  37. Erzegovesi S, Cavallini M, Cavedini P, Diaferia G, Locatelli M, Bellodi L. Clinical predictors of drug response in obsessive-compulsive disorder. J Clin Psychopharmacol. 2001;21:488–92.

    Article  CAS  PubMed  Google Scholar 

  38. Catapano F, Perris F, Fabrazzo M, Cioffi V, Giacco D, De Santis V, et al. Obsessive-compulsive disorder with poor insight: a three-year prospective study. Prog Neuro-Psychopharmacology Biol Psychiatry. 2010;34:323–30.

    Article  Google Scholar 

  39. Reid J, Reghunandanan S, Roberts A, Fineberg NA. Standard evidence-based pharmacological treatment for OCD. In: Pittenger C, editor. Obsessive-compulsive disorder: Phenomenology, pathophysiology, and treatment. 1st ed. New York: Oxford University Press; 2017. p. 443–61.

    Google Scholar 

  40. Wheaton MG, Galfalvy H, Steinman SA, Wall MM, Foa EB, Simpson HB. Patient adherence and treatment outcome with exposure and response prevention for OCD: which components of adherence matter and who becomes well? Behav Res Ther. 2016;85:6–12.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Dold M, Aigner M, Lanzenberger R, Kasper S. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials. Int J Neuropsychopharmacol. 2013;16:557–74.

    Article  CAS  PubMed  Google Scholar 

  42. Veale D, Miles S, Smallcombe N, Ghezai H, Goldacre B, Hodsoll J. Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis. BMC Psychiatry. 2014;14:317.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Komossa K, Depping AM, Meyer M, Kissling W, Leucht S. Second-generation antipsychotics for obsessive compulsive disorder. Cochrane Database Syst Rev. 2010; https://doi.org/10.1002/14651858.CD008141.pub2.

  44. Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006;11:622–32.

    Article  CAS  PubMed  Google Scholar 

  45. Dold M, Aigner M, Lanzenberger R, Kasper S. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: an update meta-analysis of double-blind, randomized, placebo-controlled trials. Int J Neuropsychopharmacol. 2015;18:1–11.

    Article  CAS  Google Scholar 

  46. Simpson HB. Overview of the treatment of obsessive-compulsive disorder. 1st ed. New York: Oxford University Press; 2017.

    Google Scholar 

  47. Fineberg NA, Gale TM. Evidence-based pharmacotherapy of obsessive – compulsive disorder. Int J Neuropsychopharmacol. 2005;8:107–29.

    Article  CAS  PubMed  Google Scholar 

  48. Koran LM, Gamel NN, Choung HW, Smith EH, Aboujaoude EN. Mirtazapine for obsessive-compulsive disorder: an open trial followed by double-blind discontinuation. J Clin Psychiatry. 2005;66:515–20.

    Article  CAS  PubMed  Google Scholar 

  49. McKay D, Sookman D, Neziroglu F, Wilhelm S, Stein DJ, Kyrios M, et al. Efficacy of cognitive-behavioral therapy for obsessive-compulsive disorder. Psychiatry Res. 2015;227:104–13.

    Article  PubMed  Google Scholar 

  50. Simpson HB, Maher MJ, Wang Y, Bao Y, Foa EB, Franklin M. Patient adherence predicts outcome from cognitive behavioral therapy in obsessive-compulsive disorder. J Consult Clin Psychol. 2011;79:247–52.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Albert U, Aguglia A, Bogetto F, Cieri L, Daniele M, Maina G, et al. Effectiveness of cognitive-behavioral therapy addition to pharmacotherapy in resistant obsessive-compulsive disorder: a multicenter study. Psychother Psychosom. 2012;81:383–5.

    Article  PubMed  Google Scholar 

  52. Zitterl W, Demal U, Aigner M, Lenz G, Urban C, Zapotoczky H-G, et al. Naturalistic course of obsessive compulsive disorder and comorbid depression. Psychopathology. 2000;33:75–80.

    Article  CAS  PubMed  Google Scholar 

  53. Olatunji BO, Davis ML, Powers MB, Smits JAJ. Cognitive-behavioral therapy for obsessive-compulsive disorder: a meta-analysis of treatment outcome and moderators. J Psychiatr Res. 2013;47:33–41.

    Article  PubMed  Google Scholar 

  54. Foa EB, Abramowitz JS, Franklin ME, Kozak MJ. Feared consequences, fixity of belief, and treatment outcome in patients with obsessive-compulsive disorder. Behav Ther. 1999;30:717–24.

    Article  Google Scholar 

  55. Eisen JL, Rasmussen SA, Phillips KA, Price LH, Davidson J, Lydiard RB, et al. Insight and treatment outcome in obsessive-compulsive disorder. Compr Psychiatry. 2001;42:494–7.

    Article  CAS  PubMed  Google Scholar 

  56. Abramowitz J. The psychological treatment of obsessive compulsive disorder. Can J Psychiatr. 2006;51:407–16.

    Article  Google Scholar 

  57. Gillihan SJ, Williams MT, Malcoun E, Yadin E, Foa EB. Journal of obsessive-compulsive and related disorders common pitfalls in exposure and response prevention (EX/RP) for OCD. J Obsessive Compuls Relat Disord. 2012;1:251–7.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Maher M, Ph D, Huppert JD, Chen H, Foa EB, Liebowitz MR, et al. Compulsive Disord. 2014;40:2013–23.

    Google Scholar 

  59. Marks IM, Lelliott P, Basoglu M, Noshirvani H, Monteiro W, Cohen D, et al. Clomipramine, self-exposure and therapist-aided exposure for obsessive-compulsive rituals. Br J Psychiatry. 1988;152:522. LP-534

    Article  CAS  PubMed  Google Scholar 

  60. Wheaton MG, Rosenfield D, Foa EB, Simpson HB. Augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: what moderates improvement? J Consult Clin Psychol. 2015;83:926–37.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Knopp J, Knowles S, Bee P, Lovell K, Bower P. A systematic review of predictors and moderators of response to psychological therapies in OCD: do we have enough empirical evidence to target treatment? Clin Psychol Rev. 2013;33:1067–81.

    Article  PubMed  Google Scholar 

  62. Abramowitz J, Foa E, Franklin M. Exposure and ritual prevention for obsessive-compulsive disorder: effects of intensive versus twice-weekly sessions. J Consult Clin Psychol. 2003;71:394–8.

    Article  PubMed  Google Scholar 

  63. Leonard RC, Franklin ME, Wetterneck CT, Riemann BC, Simpson HB, Kinnear K, et al. Residential treatment outcomes for adolescents with obsessive-compulsive disorder. Psychother Res. 2016;26:727–36.

    Article  PubMed  Google Scholar 

  64. Stewart SE, Stack DE, Farrell C, Pauls DL, Jenike MA. Effectiveness of intensive residential treatment (IRT) for severe, refractory obsessive-compulsive disorder. J Psychiatr Res. 2005;39:603–9.

    Article  PubMed  Google Scholar 

  65. Stewart E. Obsessive-compulsive disorder. In: Camprodon J, Rauch S, Greenberg B, Dougherty D, editors. Psychiatric neurotherapeutics. New York: Humana Press; 2016. p. 23–50.

    Chapter  Google Scholar 

  66. Whittal M. Cognitive Therapy for OCD. In: Pittenger C, editor. Obsessive-compulsive disorder: Phenomenology, pathophysiology, and treatment. 1st ed. New York: Oxford University Press; 2017. p. 421–9.

    Google Scholar 

  67. Wilhelm S, Berman N, Keshaviah A, Schwartz R, Steketee G. Mechanisms of change in cognitive therapy for obsessive compulsive disorder: role of maladaptive beliefs and schemas. Behav Res Ther. 2015;65:5–10.

    Article  PubMed  Google Scholar 

  68. Jaafari N, Rachid F, Rotge JY, Polosan M, El-Hage W, Belin D, et al. Safety and efficacy of repetitive transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder: a review. World J Biol Psychiatry. 2012;13:164–77.

    Article  PubMed  Google Scholar 

  69. Berlim MT, Van Den Eynde F, Daskalakis ZJ. Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (RTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials. Depress Anxiety. 2013;30:614–23.

    Article  PubMed  Google Scholar 

  70. Lapidus KAB, Stern ER, Berlin HA, Goodman WK. Neuromodulation for obsessive-compulsive disorder. Neurotherapeutics. 2014;11:485–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Bourne SK, Eckhardt CA, Sheth SA, Eskandar EN. Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits. Front Integr Neurosci. 2012;6:1–14.

    Article  Google Scholar 

  72. Cleary DR, Ozpinar A, Raslan AM, Ko AL. Deep brain stimulation for psychiatric disorders: where we are now. Neurosurg Focus. 2015;38:E2.

    Article  PubMed  Google Scholar 

  73. Alonso P, Cuadras D, Gabriëls L, et al. Deep brain stimulation for obsessive-compulsive disorder: a meta-analysis of treatment outcome and predictors of response. PLoS One. 2015;10:1–16.

    Google Scholar 

  74. Greenberg BD, Price LH, Rauch SL, Friehs G, Noren G, Malone D, et al. Neurosurgery for intractable obsessive-compulsive disorder and depression: critical issues. Neurosurg Clin N Am. 2003;14:199–212.

    Article  PubMed  Google Scholar 

  75. Brown LT, Mikell CB, Youngerman BE, Zhang Y, Ii GMM, Sheth SA. System Rev Observational Stud. 2015;124:77–89.

    Google Scholar 

  76. Sheth SA, Neal J, Tangherlini F, Mian MK, Gentil A, Rees Cosgrove G, et al. Limbic system surgery for treatment-refractory obsessive-compulsive disorder: a prospective long-term follow-up of 64 patients. J Neurosurg. 2013;118:491–7.

    Article  PubMed  Google Scholar 

  77. Lopes AC, Greenberg BD, Canteras MM, et al. Gamma ventral capsulotomy for obsessive-compulsive disorder: a randomized clinical trial. JAMA Psychiat. 2014;71:1066–76.

    Article  Google Scholar 

  78. Keen E, Widge A, Dougherty DD. Functional neurosurgery in severe and treatment-refractory OCD. In: Pittenger C, editor. Obsessive-compulsive disorder: Phenomenology, pathophysiology, and treatment. 1st ed. New York: Oxford University Press; 2017. p. 507–16.

    Google Scholar 

  79. Rück C, Karlsson A, Steele J, et al. Capsulotomy for obsessive-compulsive disorder: long-term follow-up of 25 patients. Arch Gen Psychiatry. 2008;65:914–21.

    Article  PubMed  Google Scholar 

  80. Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012;16:43–51.

    Article  PubMed  Google Scholar 

  81. Milad MR, Rosenbaum BL, Simon NM. Neuroscience of fear extinction: implications for assessment and treatment of fear-based and anxiety related disorders. Behav Res Ther. 2014;62:17–23.

    Article  PubMed  Google Scholar 

  82. Gillan CM, Papmeyer M, Morein-Zamir S, Sahakian BJ, Fineberg NA, Robbins TW, et al. Disruption in the balance between goal-directed behavior and habit learning in obsessive-compulsive disorder. Am J Psychiatry. 2011;168:718–26.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Gillan CM, Robbins TW. Goal-directed learning and obsessive – compulsive disorder. Philos Trans R Soc Lond Ser B Biol Sci. 2014;369:20130475.

    Article  Google Scholar 

  84. Stern ER, Taylor SF. Cognitive neuroscience of obsessive-compulsive disorder. Psychiatr Clin NA. 2014;37:337–52.

    Article  Google Scholar 

  85. Van Den Heuvel OA, Van Wingen G, Soriano-Mas C, Alonso P, Chamberlain SR, Nakamae T, et al. Brain circuitry of compulsivity. Eur Neuropsychopharmacol. 2016;26:810–27.

    Article  CAS  Google Scholar 

  86. Fullana MA, Zhu X, Alonso P, et al. Basolateral amygdala-ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive-compulsive disorder. J Psychiatry Neurosci. 2017;42:378–85.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Boedhoe PSW, Schmaal L, Mataix-Cols D, et al. Association and causation in brain imaging in the case of OCD: response to McKay et al. Am J Psychiatry. 2017;174:597–9.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Attwells S, Setiawan E, AA W, et al. Inflammation in the neurocircuitry of obsessive-compulsive disorder. JAMA Psychiat. 2017;74:833–40.

    Article  Google Scholar 

  89. (OCGAS) IOCDFGC (IOCDF-G and OCDCGAS). Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis. Mol Psychiatry. 2017;5:1181–8.

    Google Scholar 

  90. Taylor S. Molecular genetics of obsessive–compulsive disorder: a comprehensive meta-analysis of genetic association studies. Mol Psychiatry. 2013;18:799–805.

    Article  CAS  PubMed  Google Scholar 

  91. Cappi C, Oliphant ME, Péter Z, et al. De novo damaging coding mutations are strongly associated with obsessive-compulsive disorder and overlap with autism. 2017. https://doi.org/10.1101/127712.

  92. Cappi C, Brentani H, Lima L, et al. Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways. Transl Psychiatry. 2016; https://doi.org/10.1038/tp.2016.30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hayes S, Strosahl K, Wilson K. Acceptance and commitment therapy: an experiential approach to behavior change. New York: Guilford Press; 1999.

    Google Scholar 

  94. Twohig MP, Hayes SC, Plumb JC, Pruitt LD, Collins AB, Hazlett-Stevens H, et al. A randomized clinical trial of acceptance and commitment therapy versus progressive relaxation training for obsessive compulsive disorder. J Consult Clin Psychol. 2010;78:705–16.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Strauss C, Rosten C, Hayward M, Lea L, Forrester E, Jones AM. Mindfulness-based exposure and response prevention for obsessive compulsive disorder: study protocol for a pilot randomised controlled trial. Trials. 2015; https://doi.org/10.1186/s13063-015-0664-7.

  96. Gasnier M, Pelissolo A, Bondolfi G, Pelissolo S, Tomba M, Mallet L, et al. Mindfulness-based interventions in obsessive-compulsive disorder: mechanisms of action and presentation of a pilot study. Encéphale. 2017;43:594–9.

    Article  CAS  PubMed  Google Scholar 

  97. Lafleur D, Pittenger C, Klemendi B, Gardner T, Wasylink S, Malison R, et al. N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology. 2006;164:254–6.

    Article  CAS  Google Scholar 

  98. Stewart SE, Jenike EA, Hezel DM, Stack DE, Dodman NH, Shuster L, et al. A single-blinded case-control study of memantine in severe obsessive-compulsive disorder. J Clin Psychopharmacol. 2010;30:34–9.

    Article  PubMed  Google Scholar 

  99. Rodriguez C, Bender J, Marcus S, Snape M, Rynn M, Simpson HB. Minocycline augmentation of pharmacotherapy in Obsessive Compulsive Disorder: an open-label trial. J Clin Psychiatry. 2010;71:1247–9.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013;38:2475–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Pittenger C, Bloch MH, Wasylink S, Billingslea E, Simpson R, Jakubovski E, et al. Riluzole augmentation in treatment-refractory obsessive-compulsive disorder: a pilot randomized placebo-controlled trial. J Clin Psychiatry. 2015;76:1075–84.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Gremel CM, Chancey J, Atwood B, et al. Habit formation. 2017;90:1312–24.

    Google Scholar 

  103. Lutz B, Marsicano G, Maldonado R, Hillard C. The endocannabinoid system in guarding against fear, anxiety and stress. Nat Rev Neurosci. 2015;16:705–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Nardo M, Casarotto P, Gomes F, Guimarães F. Cannabidiol reverses the mCPP-induced increase in marble-burying behavior. Fundam Clin Pharmacol. 2014;28:544–50.

    Article  CAS  PubMed  Google Scholar 

  105. Deiana S, Watanabe A, Yamasaki Y, et al. Plasma and brain pharmacokinetic profile of cannabidiol (BD), cannabidivarine (CBDV), Δ9-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behavio. Pychopharmacology (Berl). 2019;219:859–73.

    Article  CAS  Google Scholar 

  106. Casarotto P, Gomes F, Resstel L, Guimaraes F. Cannabidiol inhibitory effect on marble-burying behavior: involvement of CB1 receptors. Behav Pharmacol. 2010;21:353–8.

    Article  CAS  PubMed  Google Scholar 

  107. Gomes F, Casarotto P, Resstel L, Guimarães F. Facilitation of CB1 receptor-mediated neurotransmission decreases marble burying behavior in mice. Prog Neuro-Psychopharmacology Biol Psychiatry. 2011;35:434–8.

    Article  CAS  Google Scholar 

  108. Schindler F, Anghelescu I, Regen F, Jockers-Scherubl M. Improvement in refractory obsessive compulsive disorder with dronabinol. 2Am J Psychiatr. 2008;165:536–7.

    Google Scholar 

  109. 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;41:214–9.

    Article  CAS  PubMed  Google Scholar 

  110. Shalbafan M, Mohammadinejad P, Shariat S-V, Alavi K, Zeinoddini A, Salehi M, et al. Celecoxib as an adjuvant to fluvoxamine in moderate to severe obsessive-compulsive disorder: a double-blind, placebo-controlled. Randomized Trial Pharmacopsychiatr. 2015;48:136–40.

    CAS  Google Scholar 

  111. Narayanaswamy JC, Jose D, Chhabra H, Agarwal SM, Shrinivasa B, Hegde A, et al. Successful application of add-on transcranial direct current stimulation (tDCS) for treatment of SSRI resistant OCD. Brain Stimul. 2015; https://doi.org/10.1016/j.brs.2014.12.003.

    Article  PubMed  Google Scholar 

  112. Sundar Arumugham S, Ravi M, Sharma E, Thirthalli J, Janardhan Reddy Y. Augmentation effect of low frequency-repetitive transcranial magnetic stimulation over pre-supplementary motor area in obsessive compulsive disorder: a randomized controlled trial. Brain Stimul. 2015;8:391.

    Article  Google Scholar 

  113. Mantione M, Nieman DH, Figee M, Denys D. Cognitive–behavioural therapy augments the effects of deep brain stimulation in obsessive–compulsive disorder. Psychol Med. 2014;44:3515–22.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. New York State Psychiatric Institute/Columbia Psychiatry, Columbia University Medical Center, New York, NY, USA

    Rachel Middleton, Michael G. Wheaton, Reilly Kayser & H. Blair Simpson

  2. Barnard College, Columbia University, New York, NY, USA

    Michael G. Wheaton

Authors
  1. Rachel Middleton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael G. Wheaton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reilly Kayser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Blair Simpson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Blair Simpson .

Editor information

Editors and Affiliations

  1. Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea (Republic of)

    Yong-Ku Kim

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Middleton, R., Wheaton, M.G., Kayser, R., Simpson, H.B. (2019). Treatment Resistance in Obsessive-Compulsive Disorder. In: Kim, YK. (eds) Treatment Resistance in Psychiatry. Springer, Singapore. https://doi.org/10.1007/978-981-10-4358-1_11

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-4358-1_11

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-4357-4

  • Online ISBN: 978-981-10-4358-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation