Augmentation of Psychotherapy With D-Cycloserine in Agoraphobia

Overview

Since decades, D-Cycloserine (DCS, drug class: Oxazolidinone) is proven to be an effective antibiotic agent in the treatment of tuberculosis. Furthermore it takes action in the central nervous system as an partial agonist on NMDA receptors. Because of glutamate mediated neuronal long-term potentiation in long-term memory DCS has an augmenting effect on emotional learning, as it occurs in exposure therapy of anxiety disorders. In this context we use DCS in addition to exposure therapy as a part of cognitive behavioral therapy (CBT) in patients suffering from agoraphobia with or without panic disorder. Thereby DCS is applicated oral as a capsule of 50mg, on three consecutive therapy sessions.

Full Title of Study: “Augmentation of Exposure Therapy With D-Cycloserine in Patients With Agoraphobia With or Without Panic Disorder”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: May 2014

Detailed Description

The present study is a multicenter study with two participating institutions: The "Klinik für Psychiatrie und Psychotherapie, Charité – Universitätsmedizin Berlin" and the "ZPHU – Zentrum für Psychotherapie am Institut für Psychologie, Humboldt-Universität zu Berlin". It is a randomized, placebo-controlled and double blind study with agoraphobic patients receiving a manualized cognitive behavioral therapy. The randomization and blindness refers to medication with an antibiotic called D-Cycloserine: One group receives D-Cycloserine after exposure sessions and the other group is treated with a placebo. The aim is to find out, whether or not D-Cycloserine augments psychotherapy outcome when administered after an exposure. Altogether, 78 patients will be treated. Before therapy, all patients receive a clinical examination to ensure that no contraindications for participating (like cardiac defects or serious central nervous system diseases) are present. In the following diagnostic sessions therapists conduct standardized assessments and after four diagnostic sessions therapy starts. All patients receive six therapy sessions, whereof three consist of exposures. When exposures are successful, D-Cycloserine or Placebo is administered afterwards. At the last therapy session another clinical examination to control several parameters is conducted. One month after therapy, two follow-up sessions with assessments take place.

Interventions

  • Behavioral: CBT
    • 12 sessions of CBT (cognitive behavioral therapy) with psychoeducation and in-vivo exposure
  • Drug: D-Cycloserine
    • Administered for three times (50mg, oral) directly after exposure

Arms, Groups and Cohorts

  • Experimental: D-Cycloserine + CBT
    • Patients receiving CBT (cognitive behavioral therapy) and D-Cycloserine (3 times, 50 mg, oral) directly after an exposure
  • Placebo Comparator: Placebo + CBT
    • Patients receiving CBT (cognitive behavioral therapy) and a placebo pill (3 times, looking identical to the DCS pill) directly after an exposure

Clinical Trial Outcome Measures

Primary Measures

  • Panic- and Agoraphobia Rating Scale (PAS)
    • Time Frame: Change from Baseline to Posttreatment (5 weeks)
    • The PAS is designed for patients with agoraphobia or panic disorder who are at least 15 years old. It can be used to determine the severity of the disorder or to examine therapeutic success. There is a self-rating and a clinician-rating version available with 14 items each, yet the items are the same in both versions. Answers are given on a five-point Likert scale from “0″ to “4″ with higher scores indicating a higher severity. For determination of the severity of the disorder, 13 items are summed up, only item “U” (asking if panic attacks occur expected or unexpected) is not considered, resulting in scores between 0 and 52. There are also five sub scores if only special contents are of interest: Panic attacks, agoraphobic avoidance, anticipatory anxiety, disability, and worries about health. For the present study the German version of the questionnaire is used.

Secondary Measures

  • Beck Anxiety Inventory (BAI)
    • Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
  • Clinical Global Index (CGI)
    • Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
  • Agoraphobic Cognitions, Body Sensations Questionnaire and Mobility Inventory (AKV)
    • Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
  • Anxiety Sensitivity Index (ASI)
    • Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
  • Beck Depression Inventory first revised(BDI II)
    • Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)
  • Brief Symptom Inventory (BSI)
    • Time Frame: Change from Baseline to Posttreatment (5 weeks) and follow-up (9 weeks)

Participating in This Clinical Trial

Inclusion Criteria

  • written consent (as per AMG §40 (1) 3b)
  • diagnosis of agoraphobia; severity of the disorder due to the CGI should at least be "moderately ill"
  • age: 18-75 years
  • negative pregnancy test for premenopausal women and safe contraception (Pearlindex < 1) during the study
  • accessibility (geographical vicinity) for treatment and follow-up
  • Compliance of the patient

Exclusion Criteria

  • Known overreaction after taking of D-Cycloserine
  • Actual pharmacotherapy with ethionamides and/ or isoniazide
  • Judicial or regulatory hospitalization in a mental institution (as per AMG §40 (1) 4)
  • Severe psychiatric disorder like schizophrenia, addiction or dementia
  • acute suicidal tendency
  • epilepsy or other diseases concerning the CNS (e.g. brain tumor, encephalitis)
  • internal disease like severe hypertension, cardiac insufficiency, cardiac arrhythmia, severe dysfunction of liver or kidney, insulin-dependent diabetes mellitus or disorders of the hematopoiesis
  • lactation
  • changes in a psychopharmacotherapy or discontinuation of a pretreatment with psychoactive drugs less than 4 weeks previous to the begin of the study
  • disturbance of the day and night rhythm
  • disorder-specific psychotherapy
  • participation in another AMG-study during the last month previous to the inclusion in the study or during the participation in this study

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Charite University, Berlin, Germany
  • Collaborator
    • German Federal Ministry of Education and Research
  • Provider of Information About this Clinical Study
    • Principal Investigator: Prof. Dr. Andreas Ströhle, assistant medical director – Charite University, Berlin, Germany
  • Overall Official(s)
    • Andreas Ströhle, Prof. Dr., Principal Investigator, Charite University, Berlin, Germany

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