Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder
Condition: Panic Disorder
MeSH terms: Panic Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a 5-year double blind, randomized, controlled, trial conducted at three treatment
      sites, aimed at showing the acute and longer-term effects of DCS augmentation of
      exposure-based CBT for panic disorder relative to placebo augmentation. By demonstrating that
      DCS can enhance the results of even a brief treatment strategy, the investigators are seeking
      to validate an approach that fits well with the practice limitations and applications of CBT
      in effectiveness studies.
    

Detailed description: 
      In this application, the investigators propose to further validate and expand upon one of the
      apparent striking successes of translational research. Specifically, basic research on the
      neural circuitry underlying fear extinction led to the examination of d-cycloserine (DCS), a
      partial agonist of the NMDA receptor in the amygdala, as an agent capable of enhancing
      extinction learning (Davis et al., 2006; Davis et al., in press). Following successful
      validation of this strategy in the animal laboratory (see Ledgerwood et al., 2005; Richardson
      et al., 2004), Ressler et al. (2004) showed that single doses of d-cycloserine (DCS) could
      enhance extinction in a human exposure paradigm for height phobic adults. This exciting
      initial finding was replicated by this research team for the treatment of social anxiety
      disorder (Hofmann et al., 2006), as well as an initial pilot study of the treatment of panic
      disorder (Tolin et al., 2006). As discussed by Anderson and Insel (2006), these findings have
      the potential to foster significant advances in the treatment of anxiety disorders. The
      present study represents the further application of DCS for augmenting the effects of
      exposure-based cognitive-behavior therapy (CBT), now applied to the treatment of panic
      disorder with or without agoraphobia.

      In the current application, the investigators propose a five-year study to show the acute and
      longer-term effects of DCS augmentation of exposure-based CBT relative to placebo
      augmentation. This study is noteworthy for the use of a brief treatment strategy that has
      been shown to be successful in previous trials (e.g., Clark et al., 1999; Roy-Byrne et al.,
      2005) and has served as the basis for the DCS augmentation effect seen in a pilot study for
      this application. By demonstrating that DCS can enhance the results of even a brief treatment
      strategy, the investigators are seeking to validate an approach that fits well with the
      practice limitations and applications of CBT in effectiveness studies (e.g., Katon et al.,
      2006; Roy-Byrne et al. 2005). Furthermore, by studying the genetic predictors of the overall
      response to CBT, and DCS augmentation in particular, the investigators hope to further
      elucidate the nature of DCS augmentation and the selection of particularly responsive
      subgroups of patients in need. This agenda is in accords with "the ultimate goal of
      personalized therapy: identifying individual patterns of pathophysiology that indicate which
      pharmacological or behavioral treatment will be most useful for any individual patient"
      (Anderson & Insel, 2006, p. 320).

      The study design is a double blind, randomized, controlled, trial conducted at three
      treatment sites. Patient with panic disorder will randomly receive DCS or placebo 1 hour
      prior to sessions 3-5 of a 5-session CBT protocol that includes 2 additional booster sessions
      over the course of follow-up. Patients will be enrolled over 5 years with the identical
      treatment protocol followed at each of the sites. Sites will nonetheless differ with respect
      to study management and analysis procedures.
    

Intervention name(s): d-cycloserine; placebo
Intervention type(s): Drug; Drug
Intervention description(s): 50mg; 50mg
Other intervention name(s): DCS
Intervention MeSH terms: Cycloserine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Panic Disorder; Anxiety; D-cycloserine; DCS; Cognitive Behavioral Therapy; CBT