Article

A preliminary study of D-cycloserine augmentation of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder.

Department of Pediatrics and Psychiatry, Rothman Center for Neuropsychiatry, University of South Florida, St. Petersburg, FL 33701, USA.
Biological psychiatry (Impact Factor: 9.47). 12/2010; 68(11):1073-6. DOI: 10.1016/j.biopsych.2010.07.015
Source: PubMed

ABSTRACT Research on the neural circuitry underlying fear extinction has led to the examination of D-cycloserine (DCS), a partial agonist at the N-methyl-D-aspartate receptor in the amygdala, as a method to enhance exposure therapy outcome. Preliminary results have supported the use of DCS to augment exposure therapy in adult anxiety disorders; however, no data have been reported in any childhood anxiety disorder. Thus, we sought to preliminarily examine whether weight-adjusted DCS doses (25 or 50 mg) enhanced the overall efficacy of cognitive-behavioral therapy (CBT) for pediatric obsessive-compulsive disorder (OCD).
Participants were 30 youth (aged 8-17) with a primary diagnosis of OCD. The study design was a randomized, double-blinded, placebo-controlled augmentation trial examining CBT + DCS versus CBT + Placebo (15 youth per group). All patients received seven exposure and response prevention sessions paired with DCS or placebo taken 1 hour before sessions.
Although not significantly different, compared with the CBT + Placebo group, youth in the CBT + DCS arm showed small-to-moderate treatment effects (d = .31-.47 on primary outcomes). No adverse events were recorded.
These results complement findings in adult OCD and non-OCD anxiety disorders and provide initial support for a more extensive study of DCS augmentation of CBT among youth with OCD.

1 Follower
 · 
165 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mental disorders are prevalent and lead to significant impairment. Progress toward establishing treatments has been good. However, effect sizes are small to moderate, gains may not persist, and many patients derive no benefit. Our goal is to highlight the potential for empirically-supported psychosocial treatments to be improved by incorporating insights from cognitive psychology and research on education. Our central question is: If it were possible to improve memory for content of sessions of psychosocial treatments, would outcome substantially improve? This question arises from five lines of evidence: (a) mental illness is often characterized by memory impairment, (b) memory impairment is modifiable, (c) psychosocial treatments often involve the activation of emotion, (d) emotion can bias memory and (e) memory for psychosocial treatment sessions is poor. Insights from scientific knowledge on learning and memory are leveraged to derive strategies for a transdiagnostic and transtreatment cognitive support intervention. These strategies can be applied within and between sessions and to interventions delivered via computer, the internet and text message. Additional novel pathways to improving memory include improving sleep, engaging in exercise and imagery. Given that memory processes change across the lifespan, services to children and older adults may benefit from cognitive support.
    Perspectives on Psychological Science 03/2014; 9(2):161-179. DOI:10.1177/1745691614521781 · 4.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although cognitive behavioral therapy (CBT) is a generally effective treatment for treating anxiety disorders, there is clearly still room for further improvements. Recent advances in neuroscience of extinction learning led to novel clinical strategies to augment exposure-based treatments with d-cycloserine (DCS), a partial agonist at the glycine recognition site of the glutamatergic N-methyl-D-aspartate receptor. This review provides an update on the current knowledge of DCS as an augmentation strategy of CBT for anxiety disorders. The adequacy of the CBT to be augmented, the dose of DCS, and the timing and duration of augmentation efforts all appear to be important moderating variables. Moreover, there is evidence that DCS may also augment fear memory reconsolidation if the fear level remains high after the exposure. Future studies need to examine whether DCS can augment CBT when administered after exposure in order to develop a tailored administration strategy to maximize its clinical utility.
    Current Psychiatry Reports 01/2015; 17(1):532. DOI:10.1007/s11920-014-0532-2 · 3.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pathological fear and anxiety are highly debilitating and, despite considerable advances in psychotherapy and pharmacotherapy they remain insufficiently treated in many patients with PTSD, phobias, panic and other anxiety disorders. Increasing preclinical and clinical evidence indicates that pharmacological treatments including cognitive enhancers, when given as adjuncts to psychotherapeutic approaches [cognitive behavioral therapy including extinction-based exposure therapy] enhance treatment efficacy, while using anxiolytics such as benzodiazepines as adjuncts can undermine long-term treatment success. The purpose of this review is to outline the literature showing how pharmacological interventions targeting neurotransmitter systems including serotonin, dopamine, noradrenaline, histamine, glutamate, GABA, cannabinoids, neuropeptides (oxytocin, neuropeptides Y and S, opioids) and other targets (neurotrophins BDNF and FGF2, glucocorticoids, L-type-calcium channels, epigenetic modifications) as well as their downstream signaling pathways, can augment fear extinction and strengthen extinction memory persistently in preclinical models. Particularly promising approaches are discussed in regard to their effects on specific aspects of fear extinction namely, acquisition, consolidation and retrieval, including long-term protection from return of fear (relapse) phenomena like spontaneous recovery, reinstatement and renewal of fear. We also highlight the promising translational value of the preclinial research and the clinical potential of targeting certain neurochemical systems with, for example D-cycloserine, yohimbine, cortisol, and L-DOPA. The current body of research reveals important new insights into the neurobiology and neurochemistry of fear extinction and holds significant promise for pharmacologically-augmented psychotherapy as an improved approach to treat trauma and anxiety-related disorders in a more efficient and persistent way promoting enhanced symptom remission and recovery.
    Pharmacology [?] Therapeutics 12/2014; 122. DOI:10.1016/j.pharmthera.2014.12.004 · 7.75 Impact Factor

Full-text (2 Sources)

Download
68 Downloads
Available from
May 20, 2014