Combined pharmacotherapy and cognitive-behavioral therapy for anxiety disorders: medication effects, glucocorticoids, and attenuated treatment outcomes.

Otto, Michael W.; McHugh, R. Kathryn; Kantak, Kathleen M.

doi:10.1111/j.1468-2850.2010.01198.x

Cited by 87Anxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesMemory and Neural MechanismsPsychotherapy Techniques and Applications

Combined pharmacotherapy and cognitive-behavioral therapy for anxiety disorders: medication effects, glucocorticoids, and attenuated treatment outcomes.

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Otto, Michael W., McHugh, R. Kathryn, Kantak, Kathleen M.·2010·Clinical Psychology Science and Practice

DOI 10.1111/j.1468-2850.2010.01198.xPMC PMC4743901

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Abstract

Despite the success of both pharmacologic and cognitive-behavioral interventions for the treatment of anxiety disorders, the combination of these modalities in adults has not resulted in substantial improvements in outcome relative to either strategy alone, raising questions about whether there are interfering effects that attenuate the magnitude of combination treatment benefits. In this article, we introduce an accounting of potential interference effects that expands upon arguments asserting the necessity of arousal for successful fear exposure. Specifically, recent advances in the study of the effects of cortisol on memory--suggesting that glucocorticoids are crucial to the learning of emotional material--have led us to posit that the attenuation of glucocorticoid activity by anxiolytic medications may interfere with extinction learning in exposure-based therapies. Implications for the efficacy of combination treatments for the anxiety disorders are discussed.

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Pharmacological therapies (benzodiazepine and antidepressant medications) result in response rates of 50.8-58.3% in adults with anxiety disorders.
“pharmacological therapies (benzodiazepine and antidepressant medications) resulting in response rates (typically defined as >50% decrease in symptoms relative to baseline) of 50.8–58.3% (4, 5)”
From Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees (2022) · cites this paper as [5]
The Abstract (page unavailable) reports a 50.8% response rate for fluoxetine alone in a trial involving adults with social anxiety disorder. It does not report a 58.3% rate or establish the stated range for benzodiazepine and antidepressant therapies generally; nor does the cited passage define response as a greater-than-50% symptom decrease. (LLM, conf=0.86)
Experimental — accuracy not yet measured
The combination of pharmacological and CBT approaches has not been found to result in more promising outcomes, with a response rate of 54.2%.
“Additionally, the combination of the two approaches has not been found to result in more promising outcomes, with a response rate of 54.2% (5).”
From Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees (2022) · cites this paper as [5]
The Abstract reports a 54.2% response rate for combined fluoxetine and CBT in one social-anxiety-disorder trial, compared with 51.7% for CBT alone and 50.8% for fluoxetine alone. It characterizes the broader advantage of combined treatment as modest, not absent. The claim presents the trial-specific rate without that qualification and implies no improvement. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Cognitive behavioral therapies result in response rates of 51.7-53.6% in adults with anxiety disorders.
“cognitive behavioral therapies (CBT) resulting in response rates of 51.7–53.6% (5, 6) in adults with anxiety disorders.”
From Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees (2022) · cites this paper as [5]
The Abstract reports a 51.7% response rate for CBT alone in a trial of adults with social anxiety disorder. It does not report 53.6% or establish the stated range for adults with anxiety disorders generally (searched: 53.6% and CBT response rate). (LLM, conf=0.88)
Experimental — accuracy not yet measured

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Patient Preference for Psychological vs Pharmacologic Treatment of Psychiatric Disorders: A Meta-Analytic Review
McHugh, R. K., Whitton, S. W., Peckham, A. D., Welge, J. A., & Otto, M. W. (2013) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.12r07757 · Cited by 800 · see citing works
Memory reconsolidation, emotional arousal, and the process of change in psychotherapy: New insights from brain science
Lane, R. D., Ryan, L., Nadel, L., & Greenberg, L. S. (2014) · Behavioral and Brain Sciences · doi:10.1017/s0140525x14000041 · Cited by 572 · see citing works
Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders
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
“Panic disorder patients (Otto et al., 2010c; Siegmund et al., 2011) also show faster symptom alleviation after DCS-augmented CBT. Reflecting the preclinical findings, negative outcomes were associated with short CBT sessions (Litz et al., 2012), insufficient within-session fear inhibition (Smits et…”
BackgroundMethodInfluential
D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data
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D-cycloserine Deters Reacquisition of Cocaine Self-Administration by Augmenting Extinction Learning
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Chronic Antidepressant Treatment Impairs the Acquisition of Fear Extinction
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Enhancement of psychosocial treatment with D-cycloserine: Models, moderators, and future directions
Otto, M. W., Kredlow, M. A., Smits, J. A. J., Hofmann, S. G., Tolin, D. F., de Kleine, R. A., van Minnen, A., Evins, A. E., & Pollack, M. H. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.09.007 · Cited by 70 · see citing works
RANDOMIZED TRIAL OF D-CYCLOSERINE ENHANCEMENT OF COGNITIVE-BEHAVIORAL THERAPY FOR PANIC DISORDER
Otto, M. W., Pollack, M. H., Dowd, S. M., Hofmann, S. G., Pearlson, G. D., Szuhany, K. L., Gueorguieva, R. V., Krystal, J. H., Simon, N. M., & Tolin, D. F. (2016) · Depression and Anxiety · doi:10.1002/da.22531 · Cited by 69 · see citing works
Cognitive enhancers for anxiety disorders
Hofmann, S. G., Smits, J. A. J., Asnaani, A., Gutner, C. A., & Otto, M. W. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.11.020 · Cited by 67 · see citing works
GABAergic implications in anxiety and related disorders
Arora, I., Mal, P., Arora, P., Paul, A., & Kumar, M. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150218 · Cited by 68 · see citing works
Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder
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Pharmacological enhancement of fear reduction: preclinical models
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Prevention of Recurrence After Recovery From a Major Depressive Episode With Antidepressant Medication Alone or in Combination With Cognitive Behavioral Therapy: Phase 2 of a 2-Phase Randomized Clinical Trial
DeRubeis, R. J., Zajecka, J., Shelton, R. C., Amsterdam, J. D., Fawcett, J., Xu, C., Young, P. R., Gallop, R., & Hollon, S. D. (2020) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.3900 · Cited by 48 · see citing works
De Novo Fear Conditioning Across Diagnostic Groups in the Affective Disorders: Evidence for Learning Impairments
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Do Benzodiazepines Reduce the Effectiveness of Exposure Therapy for Posttraumatic Stress Disorder?
Rosen, C. S., Greenbaum, M. A., Schnurr, P. P., Holmes, T. H., Brennan, P. L., & Friedman, M. J. (2013) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13m08592 · Cited by 44 · see citing works
The Efficacy of Psychotherapy: Focus on Psychodynamic Psychotherapy as an Example
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Neuroenhancement of Exposure Therapy in Anxiety Disorders
Hofmann, S. G., Mundy, E. A., & Curtiss, J. E. (2015) · AIMS neuroscience · doi:10.3934/neuroscience.2015.3.123 · Cited by 27 · see citing works
Therapist Behavior During Exposure Tasks Predicts Habituation and Clinical Outcome in Three Randomized Controlled Trials for Pediatric OCD
Benito, K., Machan, J. T., Freeman, J. B., Garcia, A. M., Walther, M. R., Frank, H. E., Wellen, B. C. M., Stewart, E., Edmunds, J., Sapyta, J. J., et al. (2020) · Behavior Therapy · doi:10.1016/j.beth.2020.07.004 · Cited by 27 · see citing works
Reward learning as a potential target for pharmacological augmentation of cognitive remediation for schizophrenia: a roadmap for preclinical development
Acheson, D. T., Twamley, E. W., & Young, J. W. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00103 · Cited by 26 · see citing works
Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees
Kiraga, M. K., Kuypers, K. P. C., Uthaug, M. V., Ramaekers, J. G., & Mason, N. L. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.883869 · Cited by 26 · see citing works
Cognitive enhancers for the treatment of anxiety disorders
Hofmann, S. G., Fang, A., & Gutner, C. A. (2014) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-139002 · Cited by 26 · see citing works
Memory creation and modification: Enhancing the treatment of psychological disorders.
Kredlow, M. A., Eichenbaum, H., & Otto, M. W. (2018) · American Psychologist · doi:10.1037/amp0000185 · Cited by 25 · see citing works
Pretreatment cortisol levels predict posttreatment outcomes among older adults with depression in cognitive behavioral therapy
Holland, J. M., Schatzberg, A. F., O'Hara, R. M., Marquett, R. M., & Gallagher-Thompson, D. E. (2013) · Psychiatry Research · doi:10.1016/j.psychres.2013.07.033 · Cited by 22 · see citing works
Moderators and predictors of treatment outcome in transdiagnostic group cognitive‐behavioral therapy for primary care patients with emotional disorders
González‐Blanch, C., Muñoz‐Navarro, R., Medrano, L. A., Moriana, J. A., Ruiz‐Rodríguez, P., & Vindel, A. C. (2021) · Depression and Anxiety · doi:10.1002/da.23164 · Cited by 23 · see citing works
New Developments in Cognitive-Behavioral Therapy for Social Anxiety Disorder
Stangier, U. (2016) · Current Psychiatry Reports · doi:10.1007/s11920-016-0667-4 · Cited by 20 · see citing works
Zur Rolle der Exposition bei der Therapie von Angststörungen
Mohr, C., & Schneider, S. (2015) · Verhaltenstherapie · doi:10.1159/000376614 · Cited by 19 · see citing works
Cognitive Therapy versus Fluvoxamine as a Second-Step Treatment in Obsessive-Compulsive Disorder Nonresponsive to First-Step Behavior Therapy
van Balkom, A. J. L. M., Emmelkamp, P. M. G., Eikelenboom, M., Hoogendoorn, A. W., Smit, J. H., & van Oppen, P. (2012) · Psychotherapy and Psychosomatics · doi:10.1159/000339369 · Cited by 24 · see citing works
Enhancing Psychological Interventions for Post-Traumatic Stress Disorder (PTSD) Treatment with Memory Influencing Drugs
Marchetta, E., Mancini, G. F., Morena, M., & Campolongo, P. (2022) · Current Neuropharmacology · doi:10.2174/1570159x21666221207162750 · Cited by 17 · see citing works
Antianxiety medications for the treatment of complex agoraphobia: pharmacological interventions for a behavioral condition
Perna, G., Daccò, S., Menotti, R., & Caldirola (2011) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s12979 · Cited by 18 · see citing works
Pessimistically biased perception in panic disorder during risk learning
Kim, M., Kim, S., Lee, K., & Jeong, B. (2020) · Depression and Anxiety · doi:10.1002/da.23007 · Cited by 17 · see citing works
Cognitive behavioral treatments for posttraumatic stress disorder: Empirical foundation and new directions
Koucky, E. M., Dickstein, B. D., & Chard, K. M. (2013) · CNS Spectrums · doi:10.1017/s1092852912000995 · Cited by 16 · see citing works
Combining a stellate ganglion block with prolonged exposure therapy for posttraumatic stress disorder: A nonrandomized clinical trial
Peterson, A. L., Straud, C. L., Young‐McCaughan, S., McCallin, J. P., Hoch, M. B., Roux, N. P., Koch, L. M., Lara‐Ruiz, J., Roache, J. D., Hein, J. M., et al. (2022) · Journal of Traumatic Stress · doi:10.1002/jts.22873 · Cited by 14 · see citing works
Exposure Therapy
Telch, M. J., Cobb, A. R., & Lancaster, C. L. (2014) · Wiley eBooks · doi:10.1002/9781118775349.ch35 · Cited by 14 · see citing works
The Future of D-Cycloserine and Other Cognitive Modifiers in Obsessive- Compulsive and Related Disorders
Sulkowski, M. L., GELLER, D. A., Lewin, A. B., Murphy, T. K., Andrew Mittelman, B., A., B., Brown, A., A., B., & Storch, E. (2014) · Current Psychiatry Reviews · doi:10.2174/1573400510666140619224942 · Cited by 11 · see citing works
d-Cycloserine does not enhance the effects of in vivo exposure among young people with broad-based anxiety disorders
Rapee, R. M., Jones, M. P., Hudson, J. L., Malhi, G. S., Lyneham, H. J., & Schneider, S. C. (2016) · Behaviour Research and Therapy · doi:10.1016/j.brat.2016.10.004 · Cited by 12 · see citing works
Anxiety Disorders - Assessment and Management in General Practice
Kyrios, M., Mouding, R., & Nedeljkovic, M. (2021) · The Singapore Family Physician · doi:10.33591/sfp.47.4.u1 · Cited by 12 · see citing works
A placebo-controlled randomized trial of D-cycloserine augmentation of cue exposure therapy for smoking cessation
Otto, M. W., Pachas, G. N., Cather, C., Hoeppner, S. S., Moshier, S. J., Hearon, B. A., Ward, H. B., Laffer, A., Smits, J. A. J., & Evins, A. E. (2018) · Cognitive Behaviour Therapy · doi:10.1080/16506073.2018.1476908 · Cited by 11 · see citing works
Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol
Shiroma, P. R., THURAS, P. D., Polusny, M. A., Kehle‐Forbes, S., Disner, S. G., Pardo, J. V., Gilmore, C. S., Tolly, B., Voller, E. K., McManus, E. S., et al. (2024) · Contemporary Clinical Trials · doi:10.1016/j.cct.2024.107569 · Cited by 10 · see citing works
Augmenting Treatment for Posttraumatic Stress Disorder and Co-Occurring Conditions with Oxytocin
Flanagan, J. C., & Mitchell, J. (2019) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-019-00171-1 · Cited by 10 · see citing works
Cognitive behavioral therapy for depressive disorders: Outcomes from a multi-state, multi-site primary care practice
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Authors: Otto, M. W., McHugh, R. K., & Kantak, K. M.
Affiliations: Boston University (US)
ORCID: Otto, Michael W.
McHugh, R. Kathryn
Kantak, Kathleen M.
Venue: Clinical Psychology Science and Practice
Publisher: American Psychological Association (APA)
Published: 2010-06
Volume: 17
Issue: 2
Pages: 91-103
ISSN: 0969-5893 (ISSN-L)
1468-2850
DOI: 10.1111/j.1468-2850.2010.01198.x
PMC: PMC4743901
OpenAlex: W1957546264
Cited by: 87
References: 114
Citations by year: 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 8 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 8 · 2015: 3 · 2014: 14 · 2013: 7 · 2012: 5
FWCI: 8.37
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1918 d)
Locations: Clinical Psychology Science and Practice (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R01MH081116)
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 › Psychotherapy Techniques and Applications
Keywords: anxiety disorders, glucocorticoids, cortisol, anxiolytics, extinction learning, fear extinction, exposure therapy, interference effects, emotional memory, treatment outcomes

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Combined pharmacotherapy and cognitive-behavioral therapy for anxiety disorders: medication effects, glucocorticoids, and attenuated treatment outcomes.

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