Enhancing exposure therapy for anxiety disorders, obsessive-compulsive disorder and post-traumatic stress disorder
Open accessAbstract
Translating findings from basic science, several compounds have been identified that may enhance therapeutic outcomes and/or expedite treatment gains when administered alongside exposure-based treatments. Four of these compounds (referred to as cognitive enhancers) have been evaluated in the context of randomized controlled trials for anxiety disorders (e.g., specific phobias, panic disorder, social anxiety disorder), obsessive-compulsive disorder and post-traumatic stress disorder. These cognitive enhancers include D-cycloserine, yohimbine hydrochloride, glucocorticoids and cortisol and brain-derived neurotrophic factor. There is consistent evidence that cognitive enhancers can enhance therapeutic outcomes and/or expedite treatment gains across anxiety disorders, obsessive-compulsive disorder and post-traumatic stress disorder. Emerging evidence has highlighted the importance of within-session fear habituation and between-session fear learning, which can either enhance fear extinction or reconsolidate of fear responses. Although findings from these trials are promising, there are several considerations that warrant further evaluation prior to widespread use of cognitive enhancers in exposure-based treatments. Consistent trial design and large sample sizes are important in future studies of cognitive enhancers.
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Motivational interviewing and behavioral contracts are evidence-based models used to maximize adherence to treatment plans and encourage motivation toward lasting changes.
“Motivational interviewing (MI) and behavioral contracts are evidence-based models used to maximize adherence to treatment plans and encourage motivation toward lasting changes [82,83].”
From Pre-Sleep Anxiety: Mechanisms and Therapeutic Approaches in Clinical Practice. (2026) · cites this paper as [83]
The Introduction discusses treatment discontinuation, and the Discussion mentions homework compliance in exposure therapy, but neither addresses motivational interviewing or behavioral contracts. Searches for those terms and for adherence and lasting change found no passage supporting the attributed claim; page numbers were unavailable in our copy. (LLM, conf=0.76)
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“[34] suggest that dose timing and level of fear may influence DCS-augmented exposure outcomes in PS, post hoc analyses of Tart et al.”
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BackgroundInfluentialCan fear extinction be enhanced? A review of pharmacological and behavioral findings
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Variant BDNF Val66Met polymorphism affects extinction of conditioned aversive memory
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“Indeed, animal studies demonstrate that mice withVal66Met exhibit impaired NMDA receptor-dependent synaptic plasticity [94] and impaired fear extinction that is ameliorated by systemic administration of DCS [100].”
BackgroundTemporally massed CS presentations generate more fear extinction than spaced presentations.
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“DCS administered after exposure sessions appeared to enhance the benefits of successful exposure therapy sessions (as defined by a low fear level at the end of a session), but had adverse consequences when administered after inadequate exposure session (as defined by a high fear level at the end of a session) [53].”
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“Animal studies suggest that G-CORT effects on memory consolidation are dose dependent, with moderate doses enhancing memory and higher doses potentially impairing memory consolidation [81].”
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“Although promising, additional wellpowered RCTs are needed to assess YHCL’s utility in other anxiety disorders, OCD and PTSD.”
InfluentialNoradrenergic modulation of extinction learning and exposure therapy.
Mueller, D., & Cahill, S. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.11.025 · Cited by 129 · cited 1× · see citing works
“Norepinephrine is associated with memory for emotion evoking stimuli, and its release during extinction may enhance memory formation [60,61].”
BackgroundHet, S., & Wolf, O. T. (2007) · Behavioral Neuroscience · doi:10.1037/0735-7044.121.1.11 · Cited by 128 · see citing works
Glucocorticoid Therapy-Induced Memory Deficits: Acute versus Chronic Effects
Coluccia, D., Wolf, O. T., Kollias, S., Roozendaal, B., Forster, A., & de Quervain, D. J. ‐. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4893-07.2008 · Cited by 126 · cited 1× · see citing works
“Beyond impacting memory consolidation, studies have also identified that administration of G-CORT can impair retrieval of non-fear-based memories [82,83] and fear-related memories [84–86].”
BackgroundStorch, E. A., Bussing, R., Small, B. J., Geffken, G. R., McNamara, J. P. H., Rahman, O., Lewin, A. B., Garvan, C. S., Goodman, W. K., & Murphy, T. K. (2013) · Behaviour Research and Therapy · doi:10.1016/j.brat.2013.09.007 · Cited by 125 · cited 24× · see citing works
“Although promising, additional wellpowered RCTs are needed to assess YHCL’s utility in other anxiety disorders, OCD and PTSD.”
BackgroundInfluentialSelf-citationPowers, M. B., Smits, J. A. J., Otto, M. W., Sanders, C., & Emmelkamp, P. M. G. (2009) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2009.01.001 · Cited by 122 · cited 3× · see citing works
“There were no significant group differences at posttreatment in either trial; however, the results from one trial favored YHCL with large treatment effects [73].”
BackgroundResultInfluentialHofmann, S. G., Smits, J. A. J., Rosenfield, D., Simon, N., Otto, M. W., Meuret, A. E., Marques, L., Fang, A., Tart, C., & Pollack, M. H. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12070974 · Cited by 121 · cited 2× · see citing works
“multicenter RCT that administered 12 sessions of group exposure-based CBT to 169 participants [41].”
MethodNMDA receptors and fear extinction: implications for cognitive behavioral therapy
Davis, M. (2011) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2011.13.4/mdavis · Cited by 118 · cited 3× · see citing works
“Animal studies have revealed that the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor found in the amygdala and prefrontal cortex plays a critical role in fear extinction (see Davis [22] for a detailed review).”
Holmes, A., & Quirk, G. J. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.10.003 · Cited by 107 · cited 1× · see citing works
“, medial prefrontal cortex, amygdala, hippocampus) [62,63].”
Need for speed: Evaluating slopes of OCD recovery in behavior therapy enhanced with d-cycloserine
Chasson, G. S., Buhlmann, U., Tolin, D. F., Rao, S. R., Reese, H. E., Rowley, T., Welsh, K. S., & Wilhelm, S. (2010) · Behaviour Research and Therapy · doi:10.1016/j.brat.2010.03.007 · Cited by 106 · cited 1× · see citing works
“[46] identified improvement among participants receiving DCS relative to placebo at the mid-treatment assessment, with post hoc analyses identifying that therapeutic gains were achieved more quickly for participants receiving DCS relative to placebo [54].”
The use of cognitive enhancers in animal models of fear extinction.
Kaplan, G. B., & Moore, K. (2011) · Pharmacology, Biochemistry and Behavior · doi:10.1016/j.pbb.2011.01.009 · Cited by 104 · cited 1× · see citing works
“As noradrenergic activity has been implicated in the consolidation of emotional memories [64,65], YHCL’s increase in central noradrenergic activity vis-à-vis norepinephrine may serve as the mechanism for its influence on fear extinction [66,67].”
BackgroundThe NMDA Agonist D-Cycloserine Facilitates Fear Memory Consolidation in Humans
Kalisch, R., Holt, B., Petrović, P., Martino, B. D., Klöppel, S., Büchel, C., & Dolan, R. J. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhn076 · Cited by 102 · cited 1× · see citing works
“Beyond promoting the extinction of conditioned fear [27,28], there is some evidence to suggest that DCS also facilitates the consolidation of fear learning associated with extinction training [29].”
BackgroundGLUCOCORTICOIDS ENHANCE IN VIVO EXPOSURE-BASED THERAPY OF SPIDER PHOBIA
Soravia, L. M., Heinrichs, M., Winzeler, L., Fisler, M. S., Schmitt, W. J., Horn, H., Dierks, T., Strik, W. K., Hofmann, S. G., & de Quervain, D. J. ‐. (2013) · Depression and Anxiety · doi:10.1002/da.22219 · Cited by 98 · see citing works
Kobayashi, K., Shimizu, E., Hashimoto, K., Mitsumori, M., Koike, K., Okamura, N., Koizumi, H., Ohgake, S., Matsuzawa, D., Zhang, L., et al. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2005.04.010 · Cited by 97 · cited 2× · see citing works
“[101] found that participants who exhibited at least a 40% reduction in symptom severity on the PDSS (classified as a treatment responder) exhibited significantly higher levels of BDNF serum at baseline relative to participants who were non-responders to treatment.”
BackgroundResultFarrell, L. J., Waters, A. M., Boschen, M. J., Hattingh, L., McConnell, H. W., Oar, E. L., Collings, N., Zimmer‐Gembeck, M. J., Shelton, D., Ollendick, T. H., et al. (2013) · Depression and Anxiety · doi:10.1002/da.22132 · Cited by 92 · cited 2× · see citing works
“, difficult-to-treat cases [48], patients likely to discontinue exposure treatment [109]).”
BackgroundSelf-citationSSRI adverse events: How to monitor and manage
Murphy, T. K., Segarra, A., Storch, E. A., & Goodman, W. K. (2008) · International Review of Psychiatry · doi:10.1080/09540260801889211 · Cited by 91 · cited 1× · see citing works
“Although commonly used in clinical practice, this therapeutic approach does not consistently yield greater therapeutic outcomes [12,15] and may be accompanied by adverse side effects [18].”
BackgroundSelf-citationWalker, D. L., & Davis, M. E. (2000) · Behavioral Neuroscience · doi:10.1037/0735-7044.114.6.1019 · Cited by 90 · cited 1× · see citing works
“As evidence suggests that fear learning is dependent upon neural activity in the amygdala and involves the neural transmission of glutamate through NMDA receptors [23], it is believed that acute DCS administration stimulates the NMDA glutamate synapses involved in emotional learning and strengthens extinction learning…”
BackgroundSiegmund, A., Golfels, F., Finck, C., Halisch, A., Räth, D., Plag, J., & Ströhle, A. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.01.020 · Cited by 89 · cited 3× · see citing works
“[38] did not find any significant difference between DCS and placebo-augmented exposurebased group CBT that was delivered over eight sessions (three exposure sessions) over a month.”
BackgroundMethodNoradrenergic enhancement of associative fear memory in humans
Soeter, M., & Kindt, M. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.05.003 · Cited by 87 · cited 1× · see citing works
“Similarly, when YHCL was administered during a differential fear conditioning paradigm, it was found to impair fear extinction and increased fear during a subsequent conditioning paradigm relative to placebo [71,72].”
BackgroundStorch, E. A., Merlo, L. J., Larson, M. J., Bloss, C. S., Geffken, G. R., Jacob, M. L., Murphy, T. K., & Goodman, W. K. (2007) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2007.01113.x · Cited by 86 · cited 1× · see citing works
“Indeed, there is some evidence that youth with fear-based and non-fear-based symptoms exhibit differential neuropsychological [56] and clinical outcomes [57,58].”
BackgroundSelf-citationYohimbine Enhancement of Exposure Therapy for Social Anxiety Disorder: A Randomized Controlled Trial
Smits, J. A. J., Rosenfield, D., Davis, M. L., Julian, K., Handelsman, P. R., Otto, M. W., Tuerk, P., Shiekh, M., Rosenfield, B., Hofmann, S. G., et al. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.10.008 · Cited by 86 · cited 4× · see citing works
“[75] identified that participants receiving YHCL exhibited expedited treatment gains on the LSAS relative to participants receiving placebo.”
BackgroundResultInfluentialAugmentation of exposure therapy with post-session administration of D-cycloserine
Tart, C. D., Handelsman, P. R., DeBoer, L. B., Rosenfield, D., Pollack, M. H., Hofmann, S. G., Powers, M. B., Otto, M. W., & Smits, J. A. J. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.09.024 · Cited by 75 · cited 4× · see citing works
“[33] reveal a more nuanced relationship.”
BackgroundInfluentialScheeringa, M. S., & Weems, C. F. (2014) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2013.0106 · Cited by 72 · cited 3× · see citing works
“Furthermore, when Scheeringa and Weems [52] conducted a detailed session-by-session analysis of the CPSS, they found a relatively linear decline in PTSD symptoms in the placebo group but greater variability among participants receiving DCS.”
MethodDevelopment of a Patient Adherence Scale for Exposure and Response Prevention Therapy
Simpson, H. B., Maher, M., Page, J. R., Gibbons, C. J., Franklin, M. E., & Foa, E. B. (2009) · Behavior Therapy · doi:10.1016/j.beth.2008.12.002 · Cited by 71 · cited 1× · see citing works
“Research has begun to examine components of within-session [104] and between-session exposure treatments [105], with further research needed to expand upon the preliminary findings reported in two DCS trials [53,59].”
MethodThe need for expanded monitoring of adverse events in behavioral health clinical trials
Peterson, A. L., Roache, J. D., Raj, J., & Young-McCaughan, S. (2013) · Contemporary Clinical Trials · doi:10.1016/j.cct.2012.10.009 · Cited by 70 · cited 1× · see citing works
“, enhancement of fear) among these augmentation psychotherapy trials that may go initially unnoticed [108].”
BackgroundTreatment of posttraumatic stress disorder in children and adolescents
Smith, P. A., Perrin, S. G., Dalgleish, T., Meiser‐Stedman, R., Clark, D. M., & Yule, W. (2012) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e32835b2c01 · Cited by 70 · cited 24× · see citing works
“Although promising, additional wellpowered RCTs are needed to assess YHCL’s utility in other anxiety disorders, OCD and PTSD.”
BackgroundInfluentialBontempo, A., Panza, K. E., & Bloch, M. H. (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.11r07356 · Cited by 69 · see citing works
Meyerbröker, K., Powers, M. B., van Stegeren, A. H., & Emmelkamp, P. M. G. (2011) · Psychotherapy and Psychosomatics · doi:10.1159/000329454 · Cited by 68 · see citing works
Pharmacological enhancement of exposure-based treatment in PTSD: a qualitative review
de Kleine, R. A., ROTHBAUM, B. O., & van Minnen, A. (2013) · European Journal of Psychotraumatology · doi:10.3402/ejpt.v4i0.21626 · Cited by 67 · cited 1× · see citing works
“Although prior reviews have examined the efficacy of cognitive enhancing compounds either by themselves [20] or for specific disorders [21], this review synthesizes and extends prior reports by evaluating the evidence for multiple cognitive enhancers across psychiatric conditions formerly classified as anxiety disorde…”
BackgroundROTHBAUM, B. O. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07121871 · Cited by 66 · cited 1× · see citing works
“As evidence suggests that fear learning is dependent upon neural activity in the amygdala and involves the neural transmission of glutamate through NMDA receptors [23], it is believed that acute DCS administration stimulates the NMDA glutamate synapses involved in emotional learning and strengthens extinction learning…”
BackgroundTreatment attrition during group therapy for social phobia.
Hofmann, S., & Suvak, M. K. (2006) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2006.03.005 · Cited by 66 · see citing works
Mataix‐Cols, D., Turner, C. M., Monzani, B. A., Isomura, K., Murphy, C., Krebs, G., & Heyman, I. (2013) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.113.126284 · Cited by 64 · cited 2× · see citing works
“[47] did not find a significant difference between groups at mid-treatment with results favoring participants receiving a placebo.”
ResultDeepened extinction following compound stimulus presentation: Noradrenergic modulationPreprint
Janak, P. H., & Corbit, L. H. (2010) · Learning & Memory · doi:10.1101/lm.1923211 · Cited by 60 · cited 1× · see citing works
“As noradrenergic activity has been implicated in the consolidation of emotional memories [64,65], YHCL’s increase in central noradrenergic activity vis-à-vis norepinephrine may serve as the mechanism for its influence on fear extinction [66,67].”
Backgroundd-Cycloserine as an augmentation strategy for cognitive behavioral therapy of anxiety disorders
Hofmann, S. G., Wu, J. Q., & Boettcher, H. (2013) · Biology of Mood & Anxiety Disorders · doi:10.1186/2045-5380-3-11 · Cited by 59 · cited 1× · see citing works
“Although prior reviews have examined the efficacy of cognitive enhancing compounds either by themselves [20] or for specific disorders [21], this review synthesizes and extends prior reports by evaluating the evidence for multiple cognitive enhancers across psychiatric conditions formerly classified as anxiety disorde…”
BackgroundBerger, W., Mehra, A., Lenoci, M., Metzler, T. J., Otte, C., Tarasovsky, G., Mellon, S. H., Wolkowitz, O. M., Marmar, C. R., & Neylan, T. C. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.07.008 · Cited by 53 · cited 1× · see citing works
“While the presence of the BDNF Val66Met variation did not definitively predict BDNF levels among non-clinical populations [97], BDNF and the TrkB system has been found to influence treatment outcomes in antidepressant studies [98,99].”
BackgroundNave, A. M., Tolin, D., & Stevens, M. (2012) · Journal of Clinical Psychiatry · doi:10.4088/jcp.11m07564 · Cited by 48 · cited 2× · see citing works
“Similar findings for an expedited therapeutic benefit were observed among DCS-enhanced exposures for ophidiophobia (fear of snakes) as evidenced by shorter time to complete a 13-step exposure hierarchy [36], as well as enhanced therapeutic outcome after DCS-augmented subliminal exposures for subthreshold arachnophobia…”
BackgroundResultPark, J. M., Small, B. J., GELLER, D. A., Murphy, T. K., Lewin, A. B., & Storch, E. A. (2013) · Journal of Child and Family Studies · doi:10.1007/s10826-013-9742-1 · Cited by 47 · cited 1× · see citing works
“Furthermore, as fear learning continues beyond the treatment session, it would prove informative to examine other factors such as homework compliance and its relation to improved therapeutic outcomes and expedited treatment gains [106].”
BackgroundSelf-citationFullana, M. A., Alonso, P., Gratacòs, M., Jaurrieta, N., Jiménez‐Múrcia, S., Segalàs, C., Real, E., Estivill, X., & Menchón, J. M. (2011) · European Psychiatry · doi:10.1016/j.eurpsy.2011.09.005 · Cited by 44 · cited 5× · see citing works
“[102] only included adults with OCD who were partial or non-responders to selective serotonin reuptake inhibitors.”
BackgroundMethodInfluentialDysregulation in pediatric obsessive compulsive disorder
Mcguire, J. F., Small, B. J., Lewin, A. B., Murphy, T. K., Nadai, A. S. D., Phares, V., Geffken, G. R., & Storch, E. A. (2013) · Psychiatry Research · doi:10.1016/j.psychres.2013.04.003 · Cited by 41 · cited 1× · see citing works
“, difficult-to-treat cases [48], patients likely to discontinue exposure treatment [109]).”
BackgroundSelf-citationYohimbine Challenge in Children With Anxiety Disorders
Sallee, F. R., Sethuraman, G., SINE, L. E., & Liu, H. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.8.1236 · Cited by 32 · cited 1× · see citing works
“Moreover, as YHCL has demonstrated tolerability among youth [107], future studies should examine YHCL’s enhancement ability for childhood anxiety disorders, OCD and PTSD.”
BackgroundNEUROPSYCHOLOGICAL PERFORMANCE ACROSS SYMPTOM DIMENSIONS IN PEDIATRIC OBSESSIVE COMPULSIVE DISORDER
Mcguire, J. F., Crawford, E. A., Park, J. M., Storch, E. A., Murphy, T. K., Larson, M. J., & Lewin, A. B. (2014) · Depression and Anxiety · doi:10.1002/da.22241 · Cited by 32 · cited 1× · see citing works
“Indeed, there is some evidence that youth with fear-based and non-fear-based symptoms exhibit differential neuropsychological [56] and clinical outcomes [57,58].”
BackgroundSelf-citationThe Nature, Assessment, and Treatment of Obsessive–Compulsive Disorder
Mcguire, J. F., Lewin, A. B., Horng, B., Murphy, T. K., & Storch, E. A. (2012) · Postgraduate Medicine · doi:10.3810/pgm.2012.01.2528 · Cited by 28 · cited 24× · see citing works
“Although promising, additional wellpowered RCTs are needed to assess YHCL’s utility in other anxiety disorders, OCD and PTSD.”
BackgroundInfluentialSelf-citationA HIGH-THROUGHPUT CLINICAL ASSAY FOR TESTING DRUG FACILITATION OF EXPOSURE THERAPY
Rodebaugh, T. L., Levinson, C. A., & Lenze, E. J. (2013) · Depression and Anxiety · doi:10.1002/da.22047 · Cited by 26 · cited 2× · see citing works
“In three of the four RCTs, participants receiving DCS and exposure-based treatment exhibited enhanced therapeutic outcomes at post-treatment and followup assessments on either the Liebowitz Social Anxiety Scale (LSAS) [39,40], Social Phobia and Anxiety Inventory [39,40] or the Social Phobia Scale [42].”
BackgroundWangelin, B. C., Powers, M. B., Smits, J. A. J., & Tuerk, P. W. (2013) · Contemporary Clinical Trials · doi:10.1016/j.cct.2013.08.003 · Cited by 26 · cited 24× · see citing works
“Although promising, additional wellpowered RCTs are needed to assess YHCL’s utility in other anxiety disorders, OCD and PTSD.”
BackgroundInfluentialMorgan, J. R., Caporino, N. E., Nadai, A. S. D., Truax, T. V., Lewin, A. B., Jung, L., Park, J. M., Khan, Y. A., Murphy, T. K., & Storch, E. A. (2013) · Child & Youth Care Forum · doi:10.1007/s10566-013-9196-z · Cited by 24 · cited 1× · see citing works
“Research has begun to examine components of within-session [104] and between-session exposure treatments [105], with further research needed to expand upon the preliminary findings reported in two DCS trials [53,59].”
MethodSelf-citationTwo-Factor Learning Theory: Versions One and Two.
Mowrer, O. H. (2009) · John Wiley & Sons, Inc. eBooks · doi:10.1037/10802-003 · Cited by 23 · cited 1× · see citing works
“The reduction in anxiety and distress associated with avoidance or compulsive behaviors negatively reinforces these actions and contributes to its maintenance (and enhancement) via negative reinforcement [5,6].”
BackgroundMcguire, J. F., Lewin, A. B., GELLER, D. A., Brown, A., Ramsey, K. A., Mutch, J., Andrew Mittelman, B., Micco, J. A., Jordan, C., Wilhelm, S., et al. (2012) · Neuropsychiatry · doi:10.2217/npy.12.38 · Cited by 17 · see citing works
Self-citationBDNF Val66Met homozygosity does not influence plasma BDNF levels in healthy human subjects
Luykx, J. J., Boks, M. P., Breetvelt, E., Aukes, M. F., Strengman, E., Pozzo, E. D., Dell’Osso, L., Marazziti, D., van Leeuwen, A., Vreeker, A., et al. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.12.017 · Cited by 13 · cited 1× · see citing works
“While the presence of the BDNF Val66Met variation did not definitively predict BDNF levels among non-clinical populations [97], BDNF and the TrkB system has been found to influence treatment outcomes in antidepressant studies [98,99].”
BackgroundThe Effect of D-cycloserine on Subliminal Cue Exposure in Spider Fearful Individuals
Gutner, C., Weinberger, J., & Hofmann, S. (2012) · Cognitive Behaviour Therapy · doi:10.1080/16506073.2012.711770 · Cited by 11 · see citing works
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Recent Progress in Virtual Reality Exposure Therapy for Phobias: A Systematic Review
Botella, C., Fernández-Álvarez, J., Guillén, V., García-Palacios, A., & Baños, R. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0788-4 · Cited by 460 · see citing works
Singewald, N., Schmuckermair, C., Whittle, N., Holmes, A., & Ressler, K. J. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.12.004 · Cited by 390 · see citing works
“Moreover, human carriers of the BDNF Val66Met SNP show reduced responsivity to exposure-based therapies [reviewed in (McGuire et al., 2014)], underscoring the potential role of BDNF in deficient fear extinction.”
BackgroundThe key role of extinction learning in anxiety disorders
Pittig, A., van den Berg, L., & Vervliet, B. (2015) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000220 · Cited by 124 · see citing works
Morena, M., Berardi, A., Colucci, P., Palmery, M., Trezza, V., Hill, M. N., & Campolongo, P. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.305 · Cited by 94 · see citing works
“…with the excessive retrieval or enhancing the extinction of the traumatic memory could improve the efficacy of exposure therapy by preventing spontaneous recovery (Choi et al, 2010; Hofmann, 2007; McGuire et al, 2014; de Quervain et al, 2011; Singewald et al, 2015; Trezza and Campolongo, 2013).”
BackgroundMcguire, J. F., Ricketts, E. J., Piacentini, J. C., Murphy, T. K., Storch, E. A., & Lewin, A. B. (2015) · Current Developmental Disorders Reports · doi:10.1007/s40474-015-0063-5 · Cited by 86 · see citing works
Self-citationThe role of progesterone in memory: An overview of three decades
Barros, L. A., Tufik, S. B., & Andersen, M. L. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.11.015 · Cited by 85 · see citing works
Berardi, A., Schelling, G., & Campolongo, P. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.07.024 · Cited by 75 · see citing works
“attracting the attention of clinicians and scientists [6, 32].”
BackgroundHunger promotes fear extinction by activation of an amygdala microcircuit
Verma, D., Wood, J., Lach, G., Herzog, H., Sperk, G., & Tasan, R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.163 · Cited by 69 · see citing works
“…targeting the catecholaminergic system by yohimbine or L-DOPA but also release of stress hormones, such as glucocorticoids, have been shown to facilitate fear extinction learning in rodents and humans (Fitzgerald et al., 2014; Holmes and Quirk, 2010; McGuire et al., 2014; Soravia et al., 2006).”
Mcguire, J. F., Piacentini, J. C., Scahill, L. D., Woods, D. W., Villarreal, R., Wilhelm, S., Walkup, J. T., & Peterson, A. L. (2015) · Behaviour Research and Therapy · doi:10.1016/j.brat.2015.05.006 · Cited by 70 · see citing works
Self-citationMcGuire, J. F., Orr, S. P., Essoe, J. K.-Y., McCracken, J. T., Storch, E. A., & Piacentini, J. (2016) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2016.1199276 · Cited by 67 · see citing works
“cognitive enhancers to augment therapeutic learning in CBT [15].”
Self-citationA Meta-Analysis of d-Cycloserine in Exposure-Based Treatment
Mcguire, J. F., Wu, M. S., Piacentini, J. C., McCracken, J. T., & Storch, E. A. (2016) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.15r10334 · Cited by 50 · see citing works
Self-citationTan, Y. L., Chang, V. Y. X., Ang, W. H. D., Ang, W. W., & Lau, Y. (2024) · Anxiety Stress & Coping · doi:10.1080/10615806.2024.2392195 · Cited by 49 · see citing works
“Individuals with SADs confront a feared stimulus in a planned, organized, and gradual manner (McGuire et al., 2014).”
Pineles, S. L., Nillni, Y. I., Pinna, G., Webb, A. K., Hall, K. A. A., Fonda, J. R., Irvine, J. M., King, M. W., Hauger, R. L., Resick, P. A., et al. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100225 · Cited by 41 · see citing works
“, a partial NMDA agonist) and have shown variable results (McGuire et al., 2014; Singewald et al., 2015).”
Evidence-based treatment of Tourette’s disorder and chronic tic disorders
Essoe, J. K.-Y., Grados, M. A., Singer, H. S., Myers, N. S., & Mcguire, J. F. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1643236 · Cited by 41 · see citing works
“enhancers such as d-cycloserine have shown promise to enhance therapeutic outcomes and/or expedite therapeutic gains when paired with psychosocial interventions [129,130].”
BackgroundSelf-citationThe Psychopharmacology of Obsessive-Compulsive Disorder: A Preclinical Roadmap
Szechtman, H., Harvey, B. H., Woody, E. Z., & Hoffman, K. L. (2019) · Pharmacological Reviews · doi:10.1124/pr.119.017772 · Cited by 40 · see citing works
Meyerbröker, K., Nexhmedin Morina, B., & Emmelkamp, P. M. G. (2018) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2018.05.001 · Cited by 34 · see citing works
Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation
Pérez-Rodríguez, M. M., New, A. S., Goldstein, K. E., Rosell, D. R., Yuan, Q., Zhou, Z., Hodgkinson, C. A., Goldman, D. A., Siever, L. J., & Hazlett, E. A. (2017) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2017.03.008 · Cited by 24 · see citing works
“Consistent with this theory, PTSD patients carrying the BDNF 66Met allele had poorer responses to exposure therapy, which is believed to be based on extinction and habituation of fear responses (Felmingham et al., 2013; McGuire et al., 2014).”
Brown, J. C., Kweon, J., Sharma, P., Siddiqi, S., Isserles, M., & Ressler, K. J. (2024) · Biological Psychiatry · doi:10.1016/j.biopsych.2024.06.010 · Cited by 21 · see citing works
Hendrikx, L. J., Krypotos, A., & Engelhard, I. M. (2020) · Journal of Behavior Therapy and Experimental Psychiatry · doi:10.1016/j.jbtep.2020.101601 · Cited by 20 · see citing works
Electrophysiological predictors of cognitive-behavioral therapy outcome in tic disorders
Morand‐Beaulieu, S., O’Connor, K. P., Blanchet, P. J., & Lavoie, M. E. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.08.020 · Cited by 20 · see citing works
PublicVR: a virtual reality exposure therapy intervention for adults with speech anxiety
Spyridonis, F., Daylamani-Zad, D., & Nightingale, J. (2024) · Virtual Reality · doi:10.1007/s10055-024-00998-x · Cited by 19 · see citing works
“A number of studies that looked into the effectiveness of Exposure Therapy have come to overall positive results showing it to be an effective method of treating psychological disorders such as SADs (Sars and van Minnen 2015; McGuire et al. 2014).”
Naß, J., & Efferth, T. (2016) · Current Neuropharmacology · doi:10.2174/1570159x15666161111113514 · Cited by 16 · see citing works
“Moreover, PTSD patients with rs6265 showed reduced responsivity to exposure-based therapies [65].”
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Self-citationNeuropeptide Y as Alternative Pharmacotherapy for Antidepressant-Resistant Social Fear
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“The best treatment outcomes are currently obtained through cognitive behavioral therapy, especially with exposure therapy, which leads to a gradual decline in the fear response because of repeated exposure to the feared situation, a process termed fear extinction [2].”
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“When addressing anxiety symptoms, completion of exercises that involve increasing approach behaviors (and reducing avoidance) could initially correspond to consistent levels of distress before eventually leading to habituation and hence reduced symptoms [38].”
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Propranolol Administration Modulates Neural Activity in the Hippocampal Hilus During Fear Retrieval
Santos, S. L., Chen, B. K., Pereira, G. R., Pham, V., & Denny, C. A. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.919831 · Cited by 7 · see citing works
“These receptors are also expressed in interneurons and, to a lesser extent, in glial cells (Booze et al., 1993; Milner et al., 2000; Guo and Li, 2007; Cox et al., 2008).”
BackgroundAdvancements in the phenomenology, assessment, and treatment of Tourette syndrome
Ramsey, K. A., & Mcguire, J. F. (2023) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000922 · Cited by 7 · see citing works
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An integrative model of perseverative thinking
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“Behavioural therapies, such as exposure (Powers and emmelkamp 2008; McGuire et al. 2014), aim to diminish the salience of triggering stimuli by reducing their associated physiological arousal. techniques like relaxation during imagery exercises and exposure to feared situations seek to…”
Saleh, A. Y., Saputra, D. A. Y., Valentina, R., & Susanto, T. D. (2025) · F1000Research · doi:10.12688/f1000research.160416.3 · Cited by 1 · see citing works
Neurobiology of Posttraumatic Stress Disorder: Circuits, Genomics, and Treatment
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5-HT Neural System Abnormalities in PTSD Model Rats
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“The importance of refining treatment guidelines to ensure fear extinction is enhanced during treatment has been noted (e.g., McGuire et al., 2014; Smits et al., 2013b).”
BackgroundThe physiological, perceptual, and thermoregulatory responses to facemask use during exercise
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Self-compassion writing facilitates fear extinction
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Development of the Response to Fearful Situations Scale
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“Although exposure therapy is an effective treatment for most anxiety disorders, it is also aversive, and questions have been raised about how to reduce attrition (McGuire et al., 2014).”
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“…models are indispensable for advancing our understanding of the neu-rocircuitry underlying AUD/PTSD comorbidity and for identifying strategies to enhance memory reconsolidation and extinction learning, ultimately aiming to improve treat - ment outcomes (Gass et al. 2014b ; McGuire et al. 2014).”
Impact of Stress and Exercise on Fear Extinction
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“It is thought to act through fear reduction and safety learning (McGuire et al., 2014).”
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Self-citationEnhancing Knowledge of Anxiety Disorders in Primary School Students Through Jigsaw Puzzle Activity
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Self-citationEffectiveness of body exposure for the treatment of body image disturbance: A meta-analysis
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- Authors
- McGuire, J. F., Lewin, A. B., & Storch, E. A.
- Affiliations
- University of South Florida (US)
- Corresponding author
- McGuire, Joseph F
- Venue
- Expert Review of Neurotherapeutics
- Publisher
- Informa UK Limited
- Published
- 2014-06-27
- Volume
- 14
- Issue
- 8
- Pages
- 893-910
- ISSN
- 1473-7175 (ISSN-L)
- 1744-8360
- PMC
- PMC4125602
- OpenAlex
- W2145081648
- Cited by
- 57
- References
- 109
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 2
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Expert Review of Neurotherapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- International OCD Foundation
- University of South Florida
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- Centers for Disease Control and Prevention
- Agency for Healthcare Research and Quality
- National Institute of Mental Health (R01MH093381)
- Janssen Pharmaceuticals
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- nootropic drugs, exposure therapy, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, D-cycloserine, yohimbine, glucocorticoids, cortisol, brain-derived neurotrophic factor, fear extinction, fear reconsolidation, fear learning, panic disorder, social anxiety disorder, specific phobia
- MeSH terms
- Animals, Anxiety Disorders, Behavior Therapy, Cycloserine, Humans, Obsessive-Compulsive Disorder, Stress Disorders, Post-Traumatic, Yohimbine, Randomized Controlled Trials as Topic
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