The first aim of the study is to investigate whether DCS addition to exposure therapy enhances symptom reduction in PD+AGO. The second objective of the study is to establish the optimal timing of administration of DCS (30 minutes before or directly…
ID
Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- PDSS scores (the Panic Disorder Severity Scale, Shear et al. 1997), measure
will be taken before sessions 4 and 8, after session 12 and after 3 and 6
months follow up.
- SUDS scores (the Subjective Unit of Distress Scale, Wolpe 1969), measured
weekly during the session.
Secondary outcome
De secondary outcome measurements will be taken before sessions 4 and 8, after
session 12 and after 3 and 6 months follow up:
- Fawcett side effects checklist (Fawcett, 1987).
- Positive and Negative Affect Shedule (PANAS).
- Mobility Inventory (MI; Chambless, 1985).
- Agoraphobis Cognitions Questionnaire (ACQ; Chambless, 1985)
- Beck anxiety Inventory (BAI; Becl. 1990)
- EQOL (Quality of Life; WHOQOL Group, 1996).
- Beck depression inventory II (BDI-II, 1987).
- Outcome questionnaire (OQ).
- Body symptoms Questionnaire (BSQ,Chambless, 1985).
- Sheenhan Disability Scales (SDS; Sheehan, 1998).
- TiC-P (Hakkaart-van Rooijen, 2002)
- The degree of extinction during the extinction task.
Background summary
Panic disorder with agoraphobia (PD+AGO) is one of the most prevalent disorders
in mental health care. Currently, behavior therapy (exposure therapy) is the
treatment of choice, either alone or in combination with antidepressiva
(SSRI's). Although exposure therapy has proven to result in symptom reduction
in about 60% of the patients, a significant number of individuals fails to
respond sufficiently to treatment.
Procedurally, exposure therapy is based on extinction of conditioned fear.
Recent work in rodents and humans has demonstrated that acute treatment with
D-cycloserine (DCS, a partial NMDA receptor agonist) enhances the learning and
memory processes underlying extinction of fear. It is of great interest to
study whether addition of DCS to exposure therapy in patients with an anxiety
disorder leads to improvement of treatment effect, speed of exposure therapy
and/or (as a consequence) diminished costs.
In patients with another anxiety disorder (the obsessive compulsive disorder)
the first clinical trials strongly suggest that DCS, administered either 1 hour
before or directly after exposure therapy, enhances the effect of the therapy
in the first 5-6 sessions. In panic disorder (the 'model' anxiety disorder) DCS
has barely been investigated, but results of the first study of enhancement
with DCS of interoceptive exposure to panic sensations suggest enhanced
treatment effect and higher remission rates in patients treated with DCS.
This study aims at extending current knowledge of exposure therapy enhancing
effects of DCS in PD+AGO.
Study objective
The first aim of the study is to investigate whether DCS addition to exposure
therapy enhances symptom reduction in PD+AGO.
The second objective of the study is to establish the optimal timing of
administration of DCS (30 minutes before or directly after exposure therapy).
The third objective is to study the fear extinction enhancement of DCS using a
neuropsychological paradigm.
The fourth objective is, from a health economic perspective, to establish
cost-effectiveness of DCS.
The hypotheses are that improvement will occur at a faster rate, with addition
of DCS, which will result in less therapy sessions needed and thus cost
reduction.
Study design
This double blind placebo controlled trial involves patients with PD+AGO,
randomized to treatment with either placebo, or single fixed dosages of 125 mg
DCS during 6 sessions of a 12 session program of ET. The exposure therapy
consists of a total of 12 sessions of 90 minutes. The first session is an
introduction session. The study medication is administered before and after
sessions 2-7, followed by 5 'regular' sessions. DCS is administered either 30
minutes before or directly after the exposure session. Thus patients with
PD+AGO will be randomly allocated to 1 of 3 possible conditions. Patients in
condition 1 will receive DCS before and placebo after ET. Patients in condition
2 will receive placebo both before and after ET. Patients in condition 3 will
receive placebo before and DCS after ET.
For patient recruitment and inclusion, departments will collaborate with the
anxiety outpatient clinic of GGZinGeest Amsterdam, GGZ Meerkanten and
GGZAltrecht. We aim to include 72 patients, because we expect this is
sufficient to include a minimal of 60 patients that fulfilled the study and can
be used in analyses.
A baseline measurement takes place to determine all in- and exclusion criteria
and to measure baseline anxiety levels to measure treatment effects.
The treatment effect on anxiety symptoms will be measured during each sessions
(using a 5 minutes questionnaire).
Several measurements are planned to measure effects of treatment on anxiety
symptoms and other outcome variables as other symptoms, possible side effects
of DCS, the use of health care and costs, quality of life, work and loss of
productivity. These measurements take place before sessions 4 and 8, after
session 12 and after 3 and 6 months follow up. The measurements consist of
questionnaires and one extinction task on the computer (during 10 minutes).
Extinction task: This task will be administered at the location of the therapy,
before session 4. To determine how DCS facilitates the process of extinction, a
version of the experimental task described by Engelhard et al (2009) will be
used. We assume that patients are already conditioned for agoraphobic stimuli.
An unconditioned stimulus is offered; a white noise of 500 ms, 95 dB. The
loudness of this tone has been tested by Engelhard et al (2009) and has been
proved to be well tolerated. Coupled with the tone (using a headphone)
agoraphobic and neutral words will be offered (using a laptop). These words
will NOT be followed by the noise and participants are asked to fill in their
expectancy of hearing the noise. Half way the experiment the tone will be
repeated to reinstate expectancy. The decrease of the expectancy will be
measured (extinction) and our hypothesis is that DCS facilitates the speed of
extinction.
Intervention
All patients receive exposure therapy (following a protocol) and part of the
patients will get additional study medication (DCS), the other part placebo.
Study burden and risks
This study can make a contribution to a better understanding of how and with
what kind of treatment panic disorder with agoraphobia could be treated better.
It is expected that this study brings little harm to the patients. The only
burden is that patients will be requested to invest some time for extra
measurements.
Risk for adverse effects of DCS are low. Research to date has shown that there
are minimal side effects at this dosage, as no side-effects have been reported
to date.
heidelberglaan 1
3584 CB, Utrecht
NL
heidelberglaan 1
3584 CB, Utrecht
NL
Listed location countries
Age
Inclusion criteria
- adult patients (between 18 and 55 years old) with panic disorder with agoraphobia (PD+AGO), according to DSM IV diagnoses as established using a standardized interview.
- patients are referred to the outpatient clinic of one of the three participating centers.
Exclusion criteria
Patients with
- comorbid psychiatric disorder (severe major depressive disorder, bipolar disorder, psychosis, dependence and/or abuse of alcohol/drugs during the past three months)
- mental deficiency
- inability to adequately read or speak Dutch
- (a history of) neurological disease (i.e. neurovascular disease, movement disorders, seizures, dementia), renal or liver abnormalities
- a history of allergies, adverse reactions or rash on medication
- currently taking benzodiazepines during the day since benzodiazepines might hamper therapy effect (use of stable dosage of evening medication is allowed)
- pregnancy or breastfeeding at the time of the study (in case of possible pregnancy, a pregnancy test will be offered)
- use of isoniazide
- use of variable dosages of antidepressiva (SSRI's or TCA's). (The use of a fixed dosage is NOT an exclusion criterium, but will be registered)
- a unsuccessful evidence based behavioral therapy for panic disorder during the past 12 months (therapy resistant patients)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2050 |
| EudraCT | EUCTR2010-021198-35-NL |
| CCMO | NL32820.041.10 |