Seattle Anxiety Specialists - Psychiatry, Psychology, and Psychotherapy

Exposure and Response Prevention (ERP)

Overview

One component of cognitive behavioral therapy (CBT), exposure and response prevention (ERP) is considered the treatment of choice for obsessive-compulsive disorder (OCD). ERP is also utilized in the treatment of various other mental health conditions, including: eating disorders; phobias; panic disorders; generalized anxiety disorders and social anxieties.[1]

Under the guidance of a therapist, clients learn the fundamental tenants of ERP. Clients “expose” themselves to the thoughts, images, objects and situations that spur anxious feelings and/or prompt one’s obsessions. During ERP, once one’s anxiety and obsessions are triggered, clients aim to make the conscious choice not to perform a compulsive behavior – this would be the “response prevention” aspect of ERP.[2]

Within the processes of ERP, one must make a commitment to not relent and engage their compulsive behaviors. While this approach may be uncomfortable until the process has been mastered by clients, over time habituation occurs, as there is a natural drop in anxiety levels when one remains exposed to their triggers while preventing their compulsive response(s).[3]

History/Development

A leading debilitating psychiatric illness,[4,5] obsessive-compulsive disorder (OCD) is characterized by distressing thoughts and repetitive behaviors that are interfering, time-consuming, and difficult to control.[6] While traditional talk therapy (i.e., psychotherapy) seeks to improve psychological conditions by helping clients gain insights into their problems, it has yet to demonstrate efficacy in treating the active symptoms of OCD.[7] In this regard, OCD was once thought to be untreatable, as clients did not respond well to traditional psychodynamic psychotherapy, medication, or behavioral interventions such as systematic desensitization or aversion therapy.[8]

In the 1970s-80s, a treatment approach dubbed “flooding” was commonly used to try to combat OCD. In the process of flooding, a person would be exposed to their worst fears very early on in therapeutic treatments. The basic principle behind flooding was the notion that anxiety levels would eventually be reduced by immersing someone in the situation one fears most, and having them stay in that situation over a period of time. While flooding has been shown to be effective if tolerated by the client, the process of forced/abrupt acclimation can be incredibly challenging mentally and physically, whereas a more-gradual introduction to one’s fears are less taxing and more tolerable to clients.[9]

In 1966, the first significant nonpharmacological advance in treatment occurred; Meyer reported OCD symptoms improved when patients were exposed to feared stimuli while simultaneously refraining from performing compulsive behaviors.[10] Further studies conducted by Foa et al. and Marks et al. indicated that this method utilizing exposure and response prevention (ERP) proved effective in both the hospital and outpatient settings, with the majority of patients experiencing significant improvement; many of whom maintained the treatment success for up to two years post-treatment.[11-13] Subsequently, ERP has become the first-line psychotherapeutic treatment for OCD.[14]

Components

An influential framework for understanding the etiology of OCD, Mowrer's two-factor theory of fear and avoidance inspired the development of behavioral treatments for the disorder, including ERP. Mowrer’s theory asserted that individuals are prone to experience anticipatory anxiety in the presence of environmental stimuli that are associated with painful or aversive experiences through classical conditioning.[15] Avoidance of feared stimuli alleviates people's anxiety, reinforcing the avoidant behavior through operant conditioning. Similarly, individuals with OCD experience anxiety-provoking obsessions triggered by various situations, thus perform compulsions and/or engage in avoidance behaviors in an effort to decrease the anxiety associated with those thoughts. Paradoxically, ritual and avoidance behaviors reinforce a one’s fear, strengthening both obsessions and compulsions.[16] The principle goal of ERP is to break the cycle of symptoms by eliminating rituals and avoidance, teaching clients methods to tolerate distress without engaging in counterproductive behaviors, further providing “corrective information” to challenge existing fear responses.[17]

Various theories have arisen regarding ERP’s mechanism of action. Early cognitive models of OCD proposed that people develop the disorder due to the misinterpretation of the significance of normal, intrusive thoughts most people experience at some point in their lives.[18,19] Group (1997) notes that varied dysfunctional thoughts have also been identified as potential etiological and maintaining factors for OCD, as these factors cause individuals to interpret intrusive thoughts as significant and potentially dangerous. Examples of such thoughts include: an inflated sense of responsibility for preventing harm to oneself and others, overestimation of threat, intolerance of uncertainty, a need for perfectionism, and over-importance of and need to control thoughts.[20] According to this perspective, ERP works by disconfirming distorted beliefs through exposure. The cognitive theory of OCD has received empirical support,[21] including from studies showing that decrements in dysfunctional thinking mediate symptom improvement post-treatment.[22] However, other studies have found that OCD severity predicts changes in dysfunctional thinking, calling into question the causal direction of change.[23] Specifically, in 2013, Olatunji et al. found that changes in OCD symptoms preceded one’s altered beliefs about their inflated responsibility, as opposed to the converse.[24]

A behavioral perspective finds that ERP breaks the conditioned response between obsessions and compulsions. Within this model, compulsions temporarily alleviate one's anxiety triggered by obsessive thoughts. By decreasing one’s distress, rituals and conditions become strengthened through continued use when one is confronted with subsequent intrusive thoughts. However, the absence of one’s feared outcome leads to the natural decrease in distress when individuals confront triggering situations while simultaneously refraining from engaging in rituals. This repeated exposure leads to a subsided fear response and diminished symptoms of OCD.[25,26]

Emotion processing theory (EPT) finds that fear and other emotions are stored in memory structures, containing information about stimuli eliciting the emotional response, as well as the response itself. EPT states that exposure therapy provides information that is contradictory to the existing fear structure when one’s dreaded outcomes do not occur. Individuals subsequently form new, more realistic memory structures without a pathological fear response. Repeated practice and exposure confronting one’s distressing situations strengthen the activation of this competing structure, weakening the occurrence of one’s fear response.[27]

More recently, a proposal has arisen indicating inhibitory learning is central to extinction through exposure therapy. This theory purports that the initial conditioned association between stimulus and the unconditioned fear response does not disappear, but that a new association is learned, competing with the former response. Therefore, the newly formed association inhibits the memory of the original excitatory response with repeated practice. Further, continued exposure to the once-feared stimuli is necessary to prevent it from being reactivated at some point again in the future.[28-30]

There has been increasing interest in the neural mechanisms underlying the etiology and treatment of psychiatric disorders, including OCD. Utilizing a neurobiological framework, Gillan and Robbins (2014) propose that compulsions are the result of excessive habit formation, as obsessions develop as one makes inferences about their behavior. When one refrains from engaging in compulsions during ERP, they begin to learn how to break habitual ritualistic behavior, thus reducing obsessions.[31] Studies examining neural mechanisms of change have identified differences in the brain from pre- to post-treatment utilizing psychotherapy.[32-34] Research has yet to identify how these changes are directly related to processes that lead to clinical improvement.[35]

Treatment Techniques

Depending on the severity of one’s symptoms, ERP can be conducted at varying levels of intensity: as outpatient; with partial hospitalization; or within residential treatment settings. Irrespective of the symptom severity, ERP is comprised of the following processes. An initial assessment is conducted, during which the clinician provides psychoeducation about OCD and treatment, and collects information about the patient's symptoms. Working in tandem, the client and clinician identify the external (situations, objects, people, etc.) and internal (thoughts and physiological reactions) stimuli that trigger a person's obsessive thoughts and corelated distress. Cataloging the specific content of one’s obsessions and compulsions, the functional relationship between the two are discussed to identify the feared outcome if one’s rituals are not performed. Working collaboratively, the client and clinician then rank different feared situations in order from least to most distressing. These situations are ranked by SUDs, or subjective units of distress, resulting in one’s fear hierarchy.[36]

As sessions progress, the clinician coaches the client as they repeatedly confront the situations comprising their fear hierarchy while simultaneously refraining from engaging in compulsions.[37] Clients will not be asked to engage in a behavior that is dangerous, that the therapist would not personally engage in, or violates their religious or moral beliefs.[38] Clients may perform physical activities and/or engage in imaginal exposures during which they envision their feared outcome triggered by obsessive thoughts. By practicing both in vivo and imaginal exposures, clients begin to learn that the consequences they fear do not occur; this leads to one more readily tolerating distress and uncertainty without engaging in compulsions.[39] If fear and anxiety remains, despite behavioral exercises, it may mean there is a neutralizing compulsion occurring, which should be discussed between the therapist and client in regards to the cognitive aspect of therapy.[40]

Following each in-session exposure, the therapist and client engage in post-exposure processing. The client's experience, expectations and what they learned are discussed during this time. Clients will also be asked to practice exposures on their own for homework, attempting to eliminate all rituals in day-to-day life. As clients habituate to various scenarios, they gradually progress up their fear hierarchy, confronting increasingly distressing situations. Following a course of ERP, relapse prevention planning typically occurs.[41,42]

Efficacy

ERP has been found to be a highly efficacious treatment for those who suffer from OCD. While a number of explanations for its mechanism of action exist, Wheaton et al. note it is still unclear exactly how this process works or why some people respond to it, whereas others do not.[43]

Early studies have demonstrated ERPs superiority in reducing clients’ OCD symptoms relative to relaxation therapy, anxiety management, or a wait-list condition. Subsequent reports further attest to its effectiveness across multiple countries, treatment settings, and intensity.[44-49] In 2004, a meta-analysis by Eddy et al. indicated that approximately two-thirds of clients receiving ERP experienced improvement in symptoms, with approximately one-third deemed recovered. Additionally, although the majority of clients treated with cognitive therapy or cognitive-behavioral therapy (without ERP) experienced a reduction in symptoms post-treatment, ERP outperformed the other treatments.[50] Specifically, Olatunji et al. noted there was a slightly stronger effect size for ERP, resulting in lower OCD severity scores post-treatment relative to the other two modalities.[51]

Research indicates that ERP is effective across a variety of settings. Its efficacy has been demonstrated in highly controlled study samples of OCD as well as in less-restricted samples with comorbidities, complicated treatment histories and those concurrently taking medication.[52,53] ERP’s generalizability is demonstrated as clients in a representative outpatient treatment setting experienced significant symptom improvement after a course of treatment. Further, a review by Storch et al. provides additional support for ERP’s utility across a variety of settings, delivered in different intensities (e.g., weekly vs. intensive treatment), as well as with pediatric and adolescent populations.[54] Moreover, ERP has been shown to reduce symptoms, decrease sleep disturbances and improve general quality of life.[55-57]

Studies have also examined the efficacy of ERP relative to and in combination with pharmacological medication. Foa et al. noted a review of four studies indicated that medication neither enhanced nor impeded treatment with ERP.[58] However, while individuals taking a combination of medication with ERP had similar outcomes to individuals in ERP alone, those solely taking medication did not improve to the degree as those on medication in combination with ERP.[59] In a subsequent study examining the combined effects of ERP with selective serotonin reuptake inhibitors, Foa et al. randomized OCD participants into one of four treatment conditions: ERP only, clomipramine only, ERP plus clomipramine, and placebo. At the end of 12 weeks, participants treated with ERP or a combination of ERP plus medication showed a greater decrease in symptoms relative to those treated with clomipramine alone. Moreover, those in the ERP plus medication condition did not differ in post-treatment symptom severity from those treated with ERP alone, indicating that medication did not bolster ERP’s efficacy.[60-62]

Additional studies have similarly tested the effectiveness of ERP as an augmentation approach for those benefitting from serotonin reuptake inhibitors (SRIs) but continue to suffer from clinically significant OCD symptoms. Simpson et al. found that patients on a stable dose of SRIs experienced greater symptom reduction after 17 weeks of ERP, compared to those who received augmentation with stress management training.[63]

Similar findings occurred when comparing augmentation with ERP to that with risperidone. Individuals taking SRIs had lower OCD severity scores immediately[64] and 6 months[65] following additional treatment with ERP than those who had additional treatment with risperidone or placebo. Further, the OCD severity of those receiving risperidone or placebo did not significantly differ from one another post-treatment.[66]

Although the current guidelines recommend ERP as the first-line treatment for OCD, only half will reach complete symptom remission.[67] Middleton et al. (2019) note a number of factors associated with poor response, including: lack of adherence to treatment; poor insight; comorbid depression and OCD severity.[68] Given the challenging and time-consuming nature of the treatment, approximately 20–30% of patients drop out of ERP prematurely.[69] Moreover, variation exists in the extent to which clients adhere to treatment recommendations, even if they do complete a full course of ERP. A 2012 study by Simpson et al. found that low adherence to completing exposures assigned between ERP sessions predicted higher symptom severity post-treatment.[70] Similarly, efficacy may be compromised if a clinician errs in the delivery of treatment.[71] Thus, ERP is most-effective when greatest fidelity to ERP occurs in both client and clinician.

Comorbid conditions have been found to impact the efficacy of ERP in the treatment of OCD. Research investigating the relationship between outcomes and factors such as insight, depression and symptom severity has yielded mixed results. While some studies have indicated that individuals with poor insight have a lower response to ERP than do those with good or fair insight, other studies found no association between the two.[72] The discrepancy in findings may be due to a restricted range of insight in OCD study samples (e.g., those with very low insight may be less likely to seek treatment for symptoms than do those with better insight.)[73]

Further, some studies have found that people suffering from severe symptoms and those with comorbid depression have worse treatment outcomes than people with no or mild depression and those with less severe OCD. Conversely, a 2013 meta-analysis by Olatunji et al.[74] reported no differences in treatment outcome effect sizes regarding depression and symptom severity. Hezel and Simpson (2019) note that one explanation for these inconsistent findings is that factors may impact treatment adherence, rather than direct outcomes. For example, individuals with poor insight may be less likely to adhere to treatment and exposure engagement compared to one who recognizes that their fears and behaviors are excessive and unrealistic.[75]

Technological advances have been used to both disseminate ERP and improve its effects. In 2010, Najmi and Amir recruited individuals with subclinical OCD contamination concerns to complete attention bias modification (ABM) before a subsequent behavioral approach task. In the attention task, half of the participants were placed in an active condition, in which they were trained to shift their attention away from perceived threatening words (e.g., related to contamination), whereas respondents in the nonactive condition did not receive such training. The authors found that individuals in the active ABM group were relatively less avoidant of contaminated objects during a subsequent behavioral approach task. They noted that reducing attention to a threat may diminish avoidance behaviors, thus leading to greater willingness to engage in exposures.[76] However, a subsequent study using a clinical population found that ABM alone did not reduce OCD symptoms; therefore, it should be utilized in addition to ERP, rather than in place of it.[77]

Although up to half of people will achieve minimal symptoms after acute treatment with ERP as either a monotherapy[78] or in combination with medication,[79,80] many who undergo ERP will remain symptomatic, with some indicating no benefit. These shortcomings highlight the possible room for improvement of ERP through enhancement of new methods, incorporation of genetic and neurobiological approaches, and development of alternative treatments.[81]

Discussion

Despite the success of ERP as a front-line treatment of OCD, the process can be improved. As afore-mentioned, many clients end treatment prematurely while a substantial number of those who do complete a course of ERP do not achieve a clinically significant reduction of symptoms. Notable challenges in the treatment of OCD include addressing the limited access to evidence-based treatments, finding novel ways to improve upon ERP to increase its efficacy, and integrating biological and psychological frameworks to adjust treatment.[82]

Regarding the numerous barriers to treatment, one solution to improve access to care is the development of an internet-based ERP program that individuals can use to guide themselves through treatment with the support of a therapist online.[83,84] Results from studies implementing ERP internet programs are promising; individuals who completed these online programs experienced a clinically significant decrease in OCD symptoms[85-87] which were maintained at follow-up.[88,89]

Virtual reality is another platform being studied as a way to enhance exposure therapy for a number of disorders, including post-traumatic stress disorder and anxiety disorders.[90,91] Although it has not been tested extensively with OCD patients, a preliminary study demonstrated its effectiveness in triggering and measuring anxiety in people through reproduced in vivo exposures.

Further, some studies have investigated possible advantages of enhancing ERP with medication implicated in facilitated extinction learning. Specifically, relative to those given a placebo pill, patients taking d-cycloserine before engaging in exposure therapy experienced a faster rate of symptom improvement in the first few weeks of receiving ERP.[92] However, a lack of group differences in symptom improvement by the end of treatment suggests that the drug's utility lies primarily in speeding up treatment response.[93]

Research on the biological underpinnings has also been sought, identifying genetic factors and abnormalities in neurocircuitry that are associated with the OCD.[94] Research has yet to bridge the gap between biological and psychological approaches in psychopathology. A notable exception would be a 2017 study by Lester et al. that identified gene variants of brain-derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH), mediating the outcome to psychotherapeutic treatment. BDNF gene codes for a protein promoting neuron development and growth, helping regulate the neurophysiological response to stress, make it especially relevant to better understand mood and anxiety disorders.[95]

FAAH, a gene in the endocannabinoid system, plays an important role in regulating anxiety and facilitating fear extinction, which is central to ERP.[96] Dincheva et al. found an association between a variant of FAAH and accelerated fear extinction in late stages of an extinction learning task as well as reduced levels of anxiety.[97] Lester et al. note this suggests the possibility to identify individuals who would be more responsive to treatments entailing extinction learning. However, a more recent study in children with anxiety disorders found limited evidence of a correlation between gene variants in the endocannabinoid system and response to CBT.[98] The assertion, therefore, is that further research on the endocannabinoid system is worthwhile.

Additionally, surgical and noninvasive neurological interventions are available to those who have not had success with psychotherapy or medication. Transcranial direct-current stimulation (tDCS) and transcranial magnetic stimulation (TMS), as well as surgical procedures such as deep brain stimulation, work to decrease symptoms by targeting the underlying neurocircuitry implicated in OCD’s pathophysiology.[99-102] Berlim et al. conducted a meta-analysis that found repetitive TMS was an effective augmentation for medication when treating refractory OCD.[103] However, none of the studies included in the meta-analysis examined TMS in combination with ERP.[104]

Since OCD is caused by a complex interaction among genetic, neurocircuitry, environmental, and developmental factors, it is essential that researchers continue to integrate psychological and biological approaches to more effectively treat this debilitating disease.[105]

Contributed by: Jennifer (Ghahari) Smith, Ph.D.

References

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2 “Exposure and Response Prevention (ERP),” International OCD Foundation. (accessed 3-26-21) iocdf.org/about-ocd/ocd-treatment/erp/

3 Ibid.

4 Baxter AJ, Vos T, Scott KM, Ferrari AJ, Whiteford HA. The global burden of anxiety disorders in 2010. Psychol Med. 2014;44:2363–74. 

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6 Association AP. Association AP. Diagnostic and Statistical Manual of Mental Disorders (DSM-5®) Arlington, VA: American Psychiatric Publishing; 2013. 

7 “Exposure and Response Prevention (ERP),” International OCD Foundation.

8 Foa EB, Yadin E, Lichner TB. Exposure and Response (Ritual) Prevention for Obsessive Compulsive Disorder: Therapist Guide. USA: Oxford University Press; 2012. 

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10 Meyer V. Modification of expectations in cases with obsessional rituals. Behav Res Ther. 1966;4:273–80.

11 Foa EB, Goldstein A. Continuous exposure and complete response prevention in the treatment of obsessive-compulsive neurosis. Behav Ther. 1978;9:821–9. 

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14 Hezel, D. M., & Simpson, H. B. (2019). Exposure and response prevention for obsessive-compulsive disorder: A review and new directions. Indian journal of psychiatry, 61(Suppl 1), S85–S92.

15 Mowrer OH. A stimulus-response analysis of anxiety and its role as a reinforcing agent. Psychol Rev. 1939;46:553–65. 

16 Hezel, D. M., & Simpson, H. B. (2019).

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25 Meyer V. (1966)

26 Hezel, D. M., & Simpson, H. B. (2019).

27 Foa EB, McLean CP. (2016)

28 Craske MG, Kircanski K, Zelikowsky M, Mystkowski J, Chowdhury N, Baker A, et al. Optimizing inhibitory learning during exposure therapy. Behav Res Ther. 2008;46:5–27. 

29 Craske MG, Treanor M, Conway CC, Zbozinek T, Vervliet B. Maximizing exposure therapy: An inhibitory learning approach. Behav Res Ther. 2014;58:10–23.

30 Hezel, D. M., & Simpson, H. B. (2019).

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

32 Linden DE. How psychotherapy changes the brain – The contribution of functional neuroimaging. Mol Psychiatry. 2006;11:528–38. 

33 Porto PR, Oliveira L, Mari J, Volchan E, Figueira I, Ventura P, et al. Does cognitive behavioral therapy change the brain? A systematic review of neuroimaging in anxiety disorders. J Neuropsychiatry Clin Neurosci. 2009;21:114–25. 

34 Saxena S, Gorbis E, O’Neill J, Baker SK, Mandelkern MA, Maidment KM, et al. Rapid effects of brief intensive cognitive-behavioral therapy on brain glucose metabolism in obsessive-compulsive disorder. Mol Psychiatry. 2009;14:197–205

35 Wheaton MG, Schwartz MR, Pascucci O, Simpson BH. Cognitive-behavior therapy outcomes for obsessive-compulsive disorder: Exposure and response prevention. Psychiatr Ann. 2015;45:303–7. 

36 Foa EB, Yadin E, Lichner TB. (2012)

37 Ibid.

38 “Exposure with Response Prevention (ERP),” Sheppard Pratt. (accessed 3-29-21) www.sheppardpratt.org/care-finder/ocd-anxiety-center/exposure-therapy-for-ocd/

39 Foa EB, Yadin E, Lichner TB. (2012)

40 “What is Exposure Response Prevention (ERP)?” OCD UK.

41 Foa EB, Yadin E, Lichner TB. (2012)

42 Hezel, D. M., & Simpson, H. B. (2019).

43 Wheaton MG, Schwartz MR, Pascucci O, Simpson BH. Cognitive-behavior therapy outcomes for obsessive-compulsive disorder: Exposure and response prevention. Psychiatr Ann. 2015;45:303–7. 

44 Abramowitz JS. Effectiveness of psychological and pharmacological treatments for obsessive-compulsive disorder: A quantitative review. J Consult Clin Psychol. 1997;65:44–52. 

45 Abramowitz JS. The psychological treatment of obsessive-compulsive disorder. Can J Psychiatry. 2006;51:407–16.

46 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;181:189–93.

47 Freeston MH, Ladouceur R, Gagnon F, Thibodeau N, Rhéaume J, Letarte H, et al. Cognitive-behavioral treatment of obsessive thoughts: A controlled study. J Consult Clin Psychol. 1997;65:405–13. 

48 Lindsay M, Crino R, Andrews G. Controlled trial of exposure and response prevention in obsessive-compulsive disorder. Br J Psychiatry. 1997;171:135–9. 

49 Storch EA, Mariaskin A, Murphy TK. Psychotherapy for obsessive-compulsive disorder. Curr Psychiatry Rep. 2009;11:296–301. 

50 Eddy KT, Dutra L, Bradley R, Westen D. A multidimensional meta-analysis of psychotherapy and pharmacotherapy for obsessive-compulsive disorder. Clin Psychol Rev. 2004;24:1011–30. 

51 Olatunji BO, Cisler JM, Deacon BJ. Efficacy of cognitive behavioral therapy for anxiety disorders: A review of meta-analytic findings. Psychiatr Clin North Am. 2010;33:557–77. 

52 Abramowitz JS. (2006)

53 Franklin ME, Abramowitz JS, Kozak MJ, Levitt JT, Foa EB. Effectiveness of exposure and ritual prevention for obsessive-compulsive disorder: Randomized compared with nonrandomized samples. J Consult Clin Psychol. 2000;68:594–602.

54 Storch EA, Mariaskin A, Murphy TK. (2009)

55 Ibid.

56 Diefenbach GJ, Abramowitz JS, Norberg MM, Tolin DF. Changes in quality of life following cognitive-behavioral therapy for obsessive-compulsive disorder. Behav Res Ther. 2007;45:3060–8. 

57 Storch EA, Murphy TK, Lack CW, Geffken GR, Jacob ML, Goodman WK, et al. Sleep-related problems in pediatric obsessive-compulsive disorder. J Anxiety Disord. 2008;22:877–85. 

58 Foa EB, Franklin ME, Moser J. Context in the clinic: How well do cognitive-behavioral therapies and medications work in combination? Biol Psychiatry. 2002;52:987–97.

59 Hezel, D. M., & Simpson, H. B. (2019).

60 Foa EB, Liebowitz MR, Kozak MJ, Davies S, Campeas R, Franklin ME, 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. 

61 Hezel, D. M., & Simpson, H. B. (2019).

62 Foa EB, McLean CP. (2016)

63 Simpson HB, Foa EB, Liebowitz MR, Ledley DR, 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.

64 Simpson HB, Foa EB, Liebowitz MR, Huppert JD, Cahill S, Maher MJ, et al. Cognitive-behavioral therapy vs risperidone for augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: A randomized clinical trial. JAMA Psychiatry. 2013;70:1190–9.

65 Foa EB, Simpson HB, Rosenfield D, Liebowitz MR, Cahill SP, Huppert JD, et al. Six-month outcomes from a randomized trial augmenting serotonin reuptake inhibitors with exposure and response prevention or risperidone in adults with obsessive-compulsive disorder. J Clin Psychiatry. 2015;76:440–6. 

66 Hezel, D. M., & Simpson, H. B. (2019).

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

68 Middleton R, Wheaton MG, Kayser R, Simpson HB. Treatment resistance in obsessive-compulsive disorder. In: Kim YK, editor. Treatment Resistance in Psychiatry. Singapore: Springer Singapore; 2019.

69 Abramowitz JS. (2006)

70 Simpson HB, Marcus SM, Zuckoff A, Franklin M, Foa EB. Patient adherence to cognitive-behavioral therapy predicts long-term outcome in obsessive-compulsive disorder. J Clin Psychiatry. 2012;73:1265–6. 

71 Gillihan SJ, Williams MT, Malcoun E, Yadin E, Foa EB. Common pitfalls in exposure and response prevention (EX/RP) for OCD. J Obsessive Compuls Relat Disord. 2012;1:251–7.

72 Middleton R, Wheaton MG, Kayser R, Simpson HB. (2019)

73 Hezel, D. M., & Simpson, H. B. (2019).

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

75 Hezel, D. M., & Simpson, H. B. (2019).

76 Najmi S, Amir N. The effect of attention training on a behavioral test of contamination fears in individuals with subclinical obsessive-compulsive symptoms. J Abnorm Psychol. 2010;119:136–42. 

77 Moritz S, Wess N, Treszl A, Jelinek A. The attention training technique as an attempt to decrease intrusive thoughts in obsessive-compulsive disorder (OCD): From cognitive theory to practice and back. J Contemp Psychother. 2011;41:135–43.

78 Foa EB, Liebowitz MR, Kozak MJ, Davies S, Campeas R, Franklin ME, et al. (2005)

79 Simpson HB, Foa EB, Liebowitz MR, Ledley DR, Huppert JD, Cahill S, et al. (2008)

80 Simpson HB, Foa EB, Liebowitz MR, Huppert JD, Cahill S, Maher MJ, et al. (2013)

81 Hezel, D. M., & Simpson, H. B. (2019).

82 Ibid.

83 Andersson E, Ljótsson B, Hedman E, Kaldo V, Paxling B, Andersson G, et al. Internet-based cognitive behavior therapy for obsessive compulsive disorder: A pilot study. BMC Psychiatry. 2011;11:125. 

84 Wootton BM, Dear BF, Johnston L, Terides MD, Titov N. Self-guided internet-delivered cognitive behavior therapy (iCBT) for obsessive-compulsive disorder: 12 month follow-up. Internet Interv. 2015;2:243–7. 

85 Patel SR, Wheaton MG, Andersson E, Rück C, Schmidt AB, La Lima CN, et al. Acceptability, feasibility, and effectiveness of internet-based cognitive-behavioral therapy for obsessive-compulsive disorder in new york. Behav Ther. 2018;49:631–41. 

86 Wootton BM, Dear BF, Johnston L, Terides MD, Titov N. (2015) 

87 Andersson E, Enander J, Andrén P, Hedman E, Ljótsson B, Hursti T, et al. (2012)

88 Wootton BM, Dear BF, Johnston L, Terides MD, Titov N. (2015)  

89 Andersson E, Steneby S, Karlsson K, Ljótsson B, Hedman E, Enander J, et al. Long-term efficacy of internet-based cognitive behavior therapy for obsessive-compulsive disorder with or without booster: A randomized controlled trial. Psychol Med. 2014;44:2877–87. 

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92 Wilhelm S, Buhlmann U, Tolin DF, Meunier SA, Pearlson GD, Reese HE, et al. Augmentation of behavior therapy with D-cycloserine for obsessive-compulsive disorder. Am J Psychiatry. 2008;165:335–41. 

93 Chasson GS, Buhlmann U, Tolin DF, Rao SR, Reese HE, Rowley T, et al. Need for speed: Evaluating slopes of OCD recovery in behavior therapy enhanced with d-cycloserine. Behav Res Ther. 2010;48:675–9. 

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96 Ibid.

97 Dincheva I, Drysdale AT, Hartley CA, Johnson DC, Jing D, King EC, et al. FAAH genetic variation enhances fronto-amygdala function in mouse and human. Nat Commun. 2015;6:6395.

98 Lester KJ, Coleman JR, Roberts S, Keers R, Breen G, Bögels S, et al. (2017)

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100 Greenberg BD, Malone DA, Friehs GM, Rezai AR, Kubu CS, Malloy PF, et al. Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology. 2006;31:2384–93. 

101 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.

102 Senço NM, Huang Y, D’Urso G, Parra LC, Bikson M, Mantovani A, et al. Transcranial direct current stimulation in obsessive-compulsive disorder: Emerging clinical evidence and considerations for optimal montage of electrodes. Expert Rev Med Devices. 2015;12:381–91. 

103 Berlim MT, Neufeld NH, Van den Eynde F. Repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD): An exploratory meta-analysis of randomized and sham-controlled trials. J Psychiatr Res. 2013;47:999–1006. 

104 Hezel, D. M., & Simpson, H. B. (2019).

105 Ibid.