Benzodiazepines and exposure-based cognitive behavior therapies for panic disorder: conclusions from combined treatment trials

Spiegel, David A.; Bruce, Timothy J.

doi:10.1176/ajp.154.6.773

Cited by 55 publications

(9 citation statements)

References 71 publications

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“…This approach, however, has revealed disappointing outcomes as benzodiazepines seem to interfere with extinction learning processes, probably involving state-dependent mechanisms ( Goldman, 1977 ; Pereira et al, 1989 ; Bouton et al, 1990 ; Bustos et al, 2009 ; Hart et al, 2014 ). In line with previous observations in animals ( Pereira et al, 1989 ; Bouton et al, 1990 ) and humans ( Spiegel and Bruce, 1997 ; Birk, 2004 ), diazepam also impaired fear extinction in LAB rats and decelerated extinction acquisition in HAB rats ( supplementary Figure 1 ), further supporting the value of the HAB/LAB model in translational research for investigating extinction-facilitating drugs. Reasons for these undesired effects of diazepam may be its sedative properties and/or state-dependency ( Birk, 2004 ; Hofmann et al, 2013 ).…”

Section: Discussionsupporting

confidence: 90%

Combined Neuropeptide S and D-Cycloserine Augmentation Prevents the Return of Fear in Extinction-Impaired Rodents: Advantage of Dual versus Single Drug Approaches

Sartori

Maurer

Murphy

et al. 2015

IJNPPY

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Background:Despite its success in treating specific anxiety disorders, the effect of exposure therapy is limited by problems with tolerability, treatment resistance, and fear relapse after initial response. The identification of novel drug targets facilitating fear extinction in clinically relevant animal models may guide improved treatment strategies for these disorders in terms of efficacy, acceleration of fear extinction, and return of fear.Methods:The extinction-facilitating potential of neuropeptide S, D-cycloserine, and a benzodiazepine was investigated in extinction-impaired high anxiety HAB rats and 129S1/SvImJ mice using a classical cued fear conditioning paradigm followed by extinction training and several extinction test sessions to study fear relapse.Results:Administration of D-cycloserine improved fear extinction in extinction-limited, but not in extinction-deficient, rodents compared with controls. Preextinction neuropeptide S caused attenuated fear responses in extinction-deficient 129S1/SvImJ mice at extinction training onset and further reduced freezing during this session. While the positive effects of either D-cycloserine or neuropeptide S were not persistent in 129S1/SvImJ mice after 10 days, the combination of preextinction neuropeptide S with postextinction D-cycloserine rendered the extinction memory persistent and context independent up to 5 weeks after extinction training. This dual pharmacological adjunct to extinction learning also protected against fear reinstatement in 129S1/SvImJ mice.Conclusions:By using the potentially nonsedative anxiolytic neuropeptide S and the cognitive enhancer D-cycloserine to facilitate deficient fear extinction, we provide here the first evidence of a purported efficacy of a dual over a single drug approach. This approach may render exposure sessions less aversive and more efficacious for patients, leading to enhanced protection from fear relapse in the long term.

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Section: Discussionsupporting

confidence: 90%

Combined Neuropeptide S and D-Cycloserine Augmentation Prevents the Return of Fear in Extinction-Impaired Rodents: Advantage of Dual versus Single Drug Approaches

Sartori

Maurer

Murphy

et al. 2015

IJNPPY

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“…We also examined whether alprazolam disrupts SI-induced resilience. Clinical trials and preclinical studies of rodents suggest that alprazolam and other benzodiazepines may diminish the efficacy of psychotherapies 19,35,36 but systematic reviews of the literature have not revealed clear-cut evidence 37–39 . We did not find support for alprazolam disruption of later resilience and show that resilience was not linearly related to the number of different stressors administered in each early life treatment condition but instead followed a quadratic J-shaped function.…”

Section: Discussionmentioning

confidence: 99%

Nonlinear relationship between early life stress exposure and subsequent resilience in monkeys

Parker

Buckmaster

Hyde

et al. 2019

Sci Rep

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Retrospective correlational studies of humans suggest that moderate but not minimal or substantial early life stress exposure promotes the development of stress inoculation-induced resilience. Here we test for a nonlinear relationship between early life stress and resilience by comparing varying “doses” of early life stress. Juvenile squirrel monkeys underwent one of five treatment conditions between 17–27 weeks of age: Stress inoculation (SI) with continuous access to mother (SI + Mom; one stress element), SI without continuous access to mother (SI; two stress elements), SI without continuous access to mother and with alprazolam injection pretreatments (SI + Alz; three stress elements), SI without continuous access to mother and with vehicle injection pretreatments (SI + Veh; three stress elements), or standard housing (No SI; zero stress elements). Alprazolam was used to test whether anxiolytic medication diminished SI effects. Subjects exposed to one or two early life stressors subsequently responded with fewer indications of anxiety (e.g., decreased maternal clinging, increased object exploration, smaller cortisol increases) compared to No SI subjects. Subjects exposed to three early life stressors did not differ on most measures from one another or from No SI subjects. These findings provide empirical support for a nonlinear J-shaped relationship between early life stress exposure and subsequent resilience.

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“…For example, benzodiazepines may interfere with behavioral interventions for anxiety disorders. (45, 46) Consequently, participants in a trial of a behavioral treatment for panic disorder may be required to refrain from nonstudy benzodiazepines.…”

Section: Introductionmentioning

confidence: 99%

Usual and Unusual Care

Freedland

Mohr

Davidson

et al. 2011

Psychosomatic Medicine

295

135

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Objective To examine the use of existing practice control groups in randomized controlled trials of behavioral interventions, and the role of extrinsic healthcare services in the design and conduct of behavioral trials. Method Selective qualitative review. Results Extrinsic healthcare services, also known as nonstudy care, have important but under-recognized effects on the design and conduct of behavioral trials. Usual care, treatment as usual, standard of care, and other existing practice control groups pose a variety of methodological and ethical challenges, but they play a vital role in behavioral intervention research. Conclusion This review highlights the need for a scientific consensus statement on control groups in behavioral trials.

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Benzodiazepines and exposure-based cognitive behavior therapies for panic disorder: conclusions from combined treatment trials

Cited by 55 publications

References 71 publications

Combined Neuropeptide S and D-Cycloserine Augmentation Prevents the Return of Fear in Extinction-Impaired Rodents: Advantage of Dual versus Single Drug Approaches

Combined Neuropeptide S and D-Cycloserine Augmentation Prevents the Return of Fear in Extinction-Impaired Rodents: Advantage of Dual versus Single Drug Approaches

Nonlinear relationship between early life stress exposure and subsequent resilience in monkeys

Usual and Unusual Care

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