Efficacy of CBT for Benzodiazepine Discontinuation in Patients with Panic Disorder: Further Evaluation
Open accessAbstract
Despite its acute efficacy for the treatment of panic disorder, benzodiazepines (BZs) are associated with a withdrawal syndrome that closely mimics anxiety sensations, leading to difficulty with treatment discontinuation and often disorder relapse. An exposure-based cognitive-behavioral treatment for BZ discontinuation, Panic Control Treatment for BZ Discontinuation (CBT) targets the fear of these sensations and has demonstrated efficacy in preventing disorder relapse and facilitating successful BZ discontinuation among patients with panic disorder. In this randomized controlled trial, CBT was compared to taper alone and a taper plus a relaxation condition to control for the effect of therapist contact and support among 47 patients with panic disorder seeking taper from BZs. Based on the primary outcome of successful discontinuation of BZ use, results indicate that adjunctive CBT provided additive benefits above both taper alone and taper plus relaxation, with consistently medium and large effect sizes over time that reached significance at the six month follow-up evaluation. The efficacy of CBT relative to either of the other taper conditions reflected very large and significant effect sizes at that time. These findings suggest that CBT provides specific efficacy for the successful discontinuation from BZs, even when controlling for therapist contact and relaxation training.
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For panic disorders, CBT quadruples the number of drug-free patients at 6 months compared with taper alone (62.5% versus 12.5%).
“or quadruples (62.5% versus 12.5%) [119] the number of drug-free patients at 6 months.”
From Cognitive behavioral therapy and acceptance and commitment therapy for the discontinuation of long-term benzodiazepine use in insomnia and anxiety disorders (2021) · cites this paper as [119]
The Results > BZ-Free Status section reports 62.5% benzodiazepine-free with CBT at six months, but 12.5% was the rate for taper plus relaxation, not taper alone. The taper-alone rate was 26.7%, so the stated comparison and “quadruples” description do not match the paper. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredInteroceptive exposure interventions aimed at anxiety sensitivity help patients endure stress, negative affect, and bodily symptoms of benzodiazepine withdrawal, with large effects.
“For example, M. W. Otto and associates have repeatedly documented the value of interoceptive exposure (IE) interventions targeting anxiety sensitivity for helping prepare patients to persist through the stress, negative affect, and somatic symptoms inherent to benzodiazepine withdrawal, with intervention effects reflecting large effect sizes (M. W. Otto et al., 1993; M. W. Otto et al., 2010; for”
From A randomized controlled trial protocol for engaging distress tolerance and working memory to aid smoking cessation in low socioeconomic status (SES) adults (2020) · cites this paper as M. W. Otto et al., 2010
The Methods describe interoceptive exposure as a component intended to reduce fear of bodily sensations associated with panic and benzodiazepine withdrawal. The Discussion reports large effects for the full CBT program on discontinuation success, not for interoceptive exposure tested on its own; neither passage has a page number in the supplied copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredTreatments that specifically target distress tolerance can prepare people in advance to cope with high stress and withdrawal sensations.
“There is evidence that treatments specifically targeting DT can help “pre-train” individuals for coping with high stress and withdrawal sensations.”
From A randomized controlled trial protocol for engaging distress tolerance and working memory to aid smoking cessation in low socioeconomic status (SES) adults (2020) · cites this paper as M. W. Otto et al., 2010
The Methods (Taper and Treatment Conditions; page not available) describe exposure-based CBT that rehearsed responses to sensations associated with panic and possible benzodiazepine withdrawal before patients began tapering. The Discussion suggests CBT helped patients continue tapering despite withdrawal symptoms. The study does not identify the treatment as specifically targeting distress tolerance or establish that it prepares people to cope with high stress generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPrior evidence indicates the interventions can activate mechanistic targets and that these targets relate to clinical outcomes at effect sizes larger than the powered values.
“Preliminary evidence shows that our interventions have the ability to activate mechanistic targets, and for mechanistic targets to be related to clinical outcomes, at effect sizes beyond these powered values (Ashare et al., 2014; M. W. Otto et al., 2010; McKee, 2009; Patterson et al., 2010; Tang et al., 2013).”
From A randomized controlled trial protocol for engaging distress tolerance and working memory to aid smoking cessation in low socioeconomic status (SES) adults (2020) · cites this paper as M. W. Otto et al., 2010
The Results (BZ-Free Status) report large effects of exposure-based CBT on benzodiazepine discontinuation at six months. The Discussion proposes that changes in anxiety sensitivity, avoidance, and safety behaviors may explain the growing treatment effects, but does not establish that those targets changed or that target changes were associated with clinical outcomes. The paper also does not compare mechanistic effect sizes with the citing study’s powered values. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCognitive behavioral therapy-based approaches have shown promise for facilitating medication discontinuation in anxiety disorders.
“CBT-based approaches have shown promise for facilitating medication discontinuation in anxiety disorders [26,27]; however, studies of OCD have remain largely unaddressed.”
From Unified protocol for the discontinuation of long-term serotonin reuptake inhibitors in obsessive compulsive disorder: Study protocol and methods (2018) · cites this paper as [26]
To date, eight RCTs comparing taper alone versus taper plus CBT and two publications reporting long-term outcomes (>24 months) have been published.
“To date, eight RCTs (see Table 1) comparing the effectiveness of a taper program alone versus a taper program associated with CBT [33,112,118,119,120,121,122,123] and two publications reporting their long-term outcomes (>24 months) have been published [124,125].”
From Cognitive behavioral therapy and acceptance and commitment therapy for the discontinuation of long-term benzodiazepine use in insomnia and anxiety disorders (2021) · cites this paper as [119]
The CBT used in these protocols, except in one study, principally targeted the conditions that initially led to BZD misuse: insomnia in people over 50, panic disorders, or generalized anxiety disorder.
“The CBT used in these protocols, with the exception of one study [121], principally targeted the conditions that initially led to the misuse of BZD: insomnia in people over 50 years old [33,122,123], panic disorders [118,119,120], or generalized anxiety disorder (GAD) [108,124].”
From Cognitive behavioral therapy and acceptance and commitment therapy for the discontinuation of long-term benzodiazepine use in insomnia and anxiety disorders (2021) · cites this paper as [119]
Clonazepam has a long elimination half-life and induced less frequently rebound anxiety than alprazolam.
“Clonazepam [73-76] has a long elimination half-life, induced less frequently rebound anxiety than alprazolam [77].”
From Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications (2020) · cites this paper as [75]
The Methods (Taper and Treatment Conditions; page unavailable) compare dosing and taper schedules for clonazepam and alprazolam, but do not state their elimination half-lives. The discussion of rebound anxiety concerns benzodiazepine withdrawal generally; no passage found compares how often the two drugs cause rebound anxiety. (LLM, conf=0.73)
Experimental — accuracy not yet measuredIn Otto 2010, risk of performance and detection bias for all outcomes was low because prescription records of BZD dose were used.
“Blinding (performance bias and detection bias) All outcomes Low risk Prescription records of dose of BZDs.”
From Psychosocial interventions for benzodiazepine harmful use, abuse or dependence (2015) · cites this paper as Otto 2010
In Otto 2010, risk of performance bias was high because there was no or incomplete blinding and the outcome was likely influenced by lack of blinding.
“Blinding of participants and personnel (performance bias) All outcomes High risk No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding”
From Psychosocial interventions for benzodiazepine harmful use, abuse or dependence (2015) · cites this paper as Otto 2010
In Otto 2010, risk of selection bias from allocation concealment was unclear because the method was not reported.
“Allocation concealment (selection bias) Unclear risk Method of allocation concealment not reported.”
From Psychosocial interventions for benzodiazepine harmful use, abuse or dependence (2015) · cites this paper as Otto 2010
In Otto 2010, risk of reporting bias was low because the published reports included all expected outcomes pre-specified in the methods section, although the protocol was unavailable.
“Selective reporting (reporting bias) Low risk The study protocol is not available but the published reports include all expected outcomes, including those that were prespecified in the method section”
From Psychosocial interventions for benzodiazepine harmful use, abuse or dependence (2015) · cites this paper as Otto 2010
DCS administration before or after exposure therapy was effective in alleviating symptoms of acrophobia, panic disorder, social anxiety disorder, and obsessive-compulsive disorder.
“Shortly thereafter, several groups reported that DCS administration before or after exposure therapy, a form of treatment based on the principles of fear extinction learning, was effective in alleviating the symptoms of acrophobia (67), panic disorder (68), social anxiety disorder (69, 70), and obsessive–compulsive disorder (71–73).”
From Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors (2014) · cites this paper as [68]
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Combined Treatment With CBT and Psychopharmacology
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“CBT-based approaches have shown promise for facilitating medication discontinuation in anxiety disorders [26,27]; however, studies of OCD have remain largely unaddressed.”
BackgroundPanic Disorder: Assessment and Treatment
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Every prescription is a prediction
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- Authors
- Otto, M. W., McHugh, R. K., Simon, N. M., Farach, F. J., Worthington, J. J., & Pollack, M. H.
- Affiliations
- Boston University (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Otto, Michael W.
- ORCID
- Venue
- Behaviour Research and Therapy
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 48
- Issue
- 8
- Pages
- 720-727
- ISSN
- 0005-7967 (ISSN-L)
- PMC
- PMC5962448
- OpenAlex
- W2106766105
- Cited by
- 95
- References
- 55
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 9 · 2013: 8 · 2012: 6
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Behaviour Research and Therapy (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R10 DA09692)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychological Treatments and Assessments
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- panic disorder, benzodiazepine discontinuation, cognitive behavioral therapy, benzodiazepine withdrawal, benzodiazepine tapering, exposure therapy, relaxation training, relapse prevention, adjunctive therapy
- MeSH terms
- Adult, Alprazolam, Benzodiazepines, Clonazepam, Dose-Response Relationship, Drug, Fear, Female, Humans, Male, Relaxation Therapy, Substance Withdrawal Syndrome, Cognitive Behavioral Therapy, Panic Disorder, Secondary Prevention
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