Enhancement of Psychosocial Treatment With D-Cycloserine: Models, Moderators, and Future Directions

Otto, Michael W.; Kredlow, M. Alexandra; Smits, Jasper A.J.; Hofmann, Stefan G.; Tolin, David F.; Kleine, Rianne A. de; Minnen, Agnes van; Evins, A. Eden; Pollack, Mark H.

doi:10.1016/j.biopsych.2015.09.007

Cited by 63 publications

(65 citation statements)

References 86 publications

(112 reference statements)

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“…These results are consistent with studies of other anxiety disorders that have shown an acceleration of treatment response with DCS augmentation, observed in the absence of an endpoint advantage when longer protocols of treatment are used 19; 20 . In contrast, endpoint advantages for DCS are more consistently observed when especially brief treatments are used, in line with the hypothesis that endpoint advantages are primarily seen when the placebo-augmented group does not have additional exposure sessions to allow them to catch up, in terms of response, to the DCS-augmented group 15 .…”

Section: Introductionsupporting

confidence: 66%

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Randomized Trial of D-Cycloserine Enhancement of Cognitive-Behavioral Therapy for Panic Disorder

et al. 2016

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Background Initial studies have provided a mixed perspective of the efficacy of d-cycloserine (DCS) for augmenting the efficacy of exposure-based cognitive behavioral therapy (CBT) for panic disorder. In this multicenter trial, we examine the magnitude of DCS augmentation effects for an ultra-brief program of CBT. Methods We conducted a double-blind, controlled trial at three treatment sites, randomizing 180 adults with a primary diagnosis of panic disorder to 5 sessions of treatment, with study pill (50 mg DCS or matching placebo) administered 1 hour prior to the final 3 sessions. Two booster sessions were subsequently provided, and outcome was assessed at post-treatment and 1-month, 2-month, and 6-month follow-up assessments. The primary outcome was the degree of reduction in the Panic Disorder Severity Scale. Additional analyses examined the role of severity and current antidepressant or benzodiazepine use as moderators of DCS augmentation effects. Results DCS augmentation resulted in significant benefit only early in the trial, with no beneficial effects of DCS augmentation evident at follow-up evaluations. We did not find that baseline severity or antidepressant or benzodiazepine use moderated DCS efficacy, but benzodiazepine use was associated with lower efficacy of CBT regardless of augmentation condition. Conclusions Consistent with other recent multicenter trials, the benefit of DCS was less than indicated by pilot study and reflected an acceleration of treatment response evident at treatment endpoint, but no advantage in response over follow-up evaluation. Our results did not support severity or concomitant medication moderators observed in previous trials of DCS augmentation. Clinical Trials Registry Name Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder (DCSPanic) Clinical Trials URL https://clinicaltrials.gov/ct2/show/NCT00790868 Clinical Trials Registry Number NCT00790868

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Section: Introductionsupporting

confidence: 66%

“…There is increasing evidence that DCS augmentation has a primary action of speeding treatment response 15 . The current study fits this pattern.…”

Section: Discussionmentioning

confidence: 99%

Randomized Trial of D-Cycloserine Enhancement of Cognitive-Behavioral Therapy for Panic Disorder

et al. 2016

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“…However, most of these trials have been conducted in adults. Additional research is needed to better understand the nuances of augmenting CBT with cognitive enhancers in youth [25,26]. …”

Section: Introductionmentioning

confidence: 99%

Extinction learning in childhood anxiety disorders, obsessive compulsive disorder and post-traumatic stress disorder: implications for treatment

McGuire

Orr

Essoe

et al. 2016

Expert Review of Neurotherapeutics

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Introduction Threat conditioning and extinction play an important role in anxiety disorders, obsessive compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). Although these conditions commonly affect children, threat conditioning and extinction have been primarily studied in adults. However, differences in phenomenology and neural architecture prohibit the generalization of adult findings to youth. Areas covered A comprehensive literature search using PubMed and PsycInfo was conducted to identify studies that have used differential conditioning tasks to examine threat acquisition and extinction in youth. The information obtained from this review helps to clarify the influence of these processes on the etiology and treatment of youth with OCD, PTSD and other anxiety disorders. Thirty studies of threat conditioning and extinction were identified. Expert Commentary Youth with anxiety disorders, OCD, and PTSD have largely comparable threat acquisition relative to unaffected controls, with some distinctions noted for youth with PTSD or youth who have suffered maltreatment. However, impaired extinction was consistently observed across youth with these disorders and appears to be consistent with deficiencies in inhibitory learning. Incorporating strategies to improve inhibitory learning may improve extinction learning within extinction-based treatments like cognitive behavioral therapy (CBT). Strategies to improve inhibitory learning in CBT are discussed.

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“…The most promise may come from the glutaminergic NMDA agonist d-cycloserine that has shown promising results in the treatment of anxiety disorders with respect to fear extinction [87]. One study tested this substance in AN in order to facilitate eating in a laboratory design and found that d-cycloserine was associated with greater caloric intake compared to no medication [88].…”

Section: Medication Studies In Anmentioning

confidence: 99%

The Role of Psychotropic Medications in the Management of Anorexia Nervosa: Rationale, Evidence and Future Prospects

Frank

Shott

2016

CNS Drugs

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Anorexia nervosa is a severe psychiatric disorder without approved medication intervention. Every class of psychoactive medication has been tried to improve treatment outcome; however, randomized controlled trials have been ambiguous at best and across studies have not shown robust improvements in weight gain and recovery. Here we review the available literature on pharmacological interventions since anorexia nervosa came to greater public recognition in the 1960s. This will include a critical review of why those trials may not have been successful. We further provide a neurobiological background for the disorder and discuss how cognition, learning and emotion-regulating circuits could become treatment targets in the future. Making every effort to develop effective pharmacological treatment options for anorexia nervosa is imperative, as it continues to be a complex psychiatric disorder with high disease burden and mortality.

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Enhancement of Psychosocial Treatment With D-Cycloserine: Models, Moderators, and Future Directions

Cited by 63 publications

References 86 publications

Randomized Trial of D-Cycloserine Enhancement of Cognitive-Behavioral Therapy for Panic Disorder

Randomized Trial of D-Cycloserine Enhancement of Cognitive-Behavioral Therapy for Panic Disorder

Extinction learning in childhood anxiety disorders, obsessive compulsive disorder and post-traumatic stress disorder: implications for treatment

The Role of Psychotropic Medications in the Management of Anorexia Nervosa: Rationale, Evidence and Future Prospects

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