Dissociative Disorders Clinical Trial
Official title:
The Interest of a Specific Combined Treatment (Psychotherapy and Pharmacotherapy) in Patients With Dissociative Disorders
The purpose of this observational study is to measure the efficacy of a specific combined treatment (psychotherapy and pharmacotherapy) on patients with dissociative disorders, in terms of patients with a favorable outcome by means of the Dissociative Experiences Scale (DES).
1. INTRODUCTION
1. Background: Dissociative Disorders are frequent, but poorly understood and
under-diagnosed [Foote et al., 2006; Spiegel, 2006], especially in psychiatric
emergency units [Lazignac et al., 2005]. The management of this is commonly mixed
up with psychotic, depressive and anxiety disorders.
The treatment of the dissociative disorders remains controversial. The
psychotherapeutic guidelines proposed by International Society for the Study of
Dissociative Disorders (ISSD) were recently adapted for the French speaking users
[Damsa et al., 2005]. There is no consensus on which antipsychotic or
antidepressant would be preferable for those patients who suffer from dissociative
disorders, accompanied by depressive or psychotic symptoms. We have a very good
clinical experience with quetiapine and escitalopram for this specific group of
patients.
2. Rationale for this study; Clinical [Lazignac et al., 2005] and neurobiological
[Kelley-Puskas et al., 2005] reviews on dissociative disorders emphasize the value
of a first open label study on the effects of specific combined psychotherapy and
pharmacotherapy in patients with dissociative disorders [Damsa et al., 2006].
2. STUDY OBJECTIVES
1. Primary objective
- The efficacy of specific combined psychotherapy and pharmacotherapy in
patients with dissociative disorders, in terms of favorable outcome (DES
scale).
2. Secondary objectives
- The efficacy of specific combined psychotherapy and pharmacotherapy in
patients with dissociative disorders, in terms of DES and CGI-I scales values.
- The effects of the combined treatment on depressive features [Hamilton
Depression Rating Scale (HDRS) and the Montgomery and Asberg Depression Rating
Scale items for suicide (MADRS)].
- The occurrence of possible extra-pyramidal side effects (Barnes Akathisia and
the Simpson and Angus Rating Scales).
- The therapeutic alliance and clinical outcome (Helping Alliance Questionnaire
of Luborsky), [Luborsky, 1976; Luborsky et al., 1996].
- The relationship between serum lipid levels and depressive symptoms.
- Tolerability and adverse effects of the quetiapine.
3. STUDY PLAN AND PROCEDURES
1. Study design. Open single arm 'pilot' clinical trial in patients with dissociative
disorders, admitted to the psychiatric emergency unit of Geneva (general capacity:
20-30 patients/day). Patients will be interviewed according to Dissociative
Experiences Scale (DES) and, if their score is 30 or higher, the Structured
Clinical Interview for DSM-IV Dissociative Disorders (SCID) will be administered.
When the outcome on the SCID is positive, the patient can be included in the study.
The Clinical Global Impression Improvement Scale (CGI-I), HDRS and the MADRS items
for suicide will be administered at entry and after 3 and 8 weeks.
The patients will be treated by a psychiatrist who has experience with the use of
the specific combined treatment for dissociative disorders [Damsa et al., 2005].
The psychiatrist decides on the antidepressant/antipsychotic medication. In our
unit the first choice for this indication is quetiapine (400 mg/d) for
antipsychotic treatment, and escitalopram (10 mg/d) as antidepressant. The
quetiapine schedule is 50-100-200-300-400-600 mg/d (min. 300 mg), then 300-600
mg/d.
Therapeutic alliance will be assessed, both by the patient and the therapist
(Luborsky scales) at the end of the first interview, and at 3 and 8 weeks. Serum
lipids levels will be measured in blood samples [Agargun et al., 2004].
2. Selection of study population
- Inclusion criteria: written informed consent, DES-score greater than 30 and
DSM-IV criteria for dissociative disorder (SCID), 18-65 years, able to comply
with the study requirements, good physical health (medical history and
physical examination). Female patients of childbearing potential must have a
negative urinary pregnancy test.
- Exclusion criteria: pregnancy/lactation, suicidal behavior requiring
hospitalization or borderline personality disorder, substance dependence,
psychotropic or cholesterol-lowering medication, intolerance or lack of
response to the study medication, unstable or inadequately treated medical
illness (angina pectoris, hypertension, congestive heart failure), involvement
in the planning and conduct of the study, participation in the present study
or in another drug trial within 4 weeks prior enrolment in study or longer in
accordance with local requirements, cytochrome P450 3A4 inhibitors and
inducers, absolute neutrophil count (ANC) equal or less than 1.5 x 109/L,
unstable Diabetes Mellitus (DM) or opposition of physician responsible for
patient's DM.
3. Discontinuation of subjects from participation
- Criteria: subject free withdrawal at any time, safety reasons, severe
non-compliance to protocol, subject lost to follow-up, development or discover
of exclusion criteria, neutrophil count of less than 1.0 x 109/L [Adverse
Event (AE) specially assessed].
- Procedures: subjects who discontinue will be asked on reason for
discontinuation. If possible, they should be assessed by investigator. The
investigational medication will be returned by the subject.
4. Treatments
- Identity of investigational product
- Doses and treatment regimens quetiapine will be used, only if patients need an
antipsychotic. Escitalopram (10 mg/day) will be used, only if patients need an
antidepressant.
Labeling of medication is in local language and complies with local regulatory
requirements.
The administration of investigational and other medication must be recorded the
appropriately.
4. OUTCOME VARIABLES
1. Primary Variable: Proportion of patients experiencing 20% DES score reduction at 8
weeks.
2. Secondary Variables:
- Change in DES score at 3 and 8 weeks.
- Dichotomized DES score (into less than 25 and equal or greater than 25)
- CGI-I score at 3 and 8 weeks
- Barnes Akathisia and Simpson-Angus Rating Scales, Helping Alliance
Questionnaire of Luborsky, Hamilton Depression Rating Scale (HDRS) and
Montgomery-Asberg Depression Rating Scale items for suicide (from baseline to
3 and 8 weeks)
- Cortisol and Lipids
- Adverse Events
3. Derived Efficacy Variables:
- Favorable outcome (at least 20% reduction of DES scores).
- Partial remission (at least 15% reduction of CGI scores).
4. Safety measurements and variables: Cardiac frequency and blood pressure.
5. DATA MANAGEMENT. The data will be confidentially treated and will be kept in a locked
room.
6. STATISTICAL METHODS AND SAMPLE SIZE
1. Description of analysis populations:
- The safety population consists of all patients who have taken at least one
quetiapine dose.
- The intention-to-treat (ITT) population consists of all patients who have
taken at least one quetiapine dose and who have at least one baseline
assessment and one post-baseline DES assessment.
- The Per-Protocol (PP) population is a subset of the ITT population, and
consists of patients who have no major protocol violations or deviations.
- Each patient will represent one observation.
2. Statistical analysis:
- The primary variable: proportion of patients who experience at least 20% DES
score reduction at 8 weeks for 95 % confidence interval.
- the change in DES score, in SAS, BARS, HAM-D and Luborsky scales and in CGI-I
will be analyzed by a model of analysis of covariance (ANCOVA).
- Changes in MADRS suicidal items scores will be illustrated by descriptive
statistics.
- The relationship between therapeutic alliance and clinical outcome and between
serum lipid levels and suicidal behavior will be analyzed by repeated measures
ANOVA.
- The DES score will be dichotomized into less than 25 and equal or greater than
25 and presented in frequency tables for each visit.
- Changes in physical examination values and laboratory values will be shown in
shift tables.
- Adverse events will be summarized and shown in frequency tables.
3. Determination of sample size: As this is a single-arm, open labeled pilot study, no
formal sample size calculation is performed. In the expected sample size of 30
patients, for the proportion of patients achieving a 20% reduction in DES score,
the confidence interval can be estimated between -18 and +18%; the drop-out
patients will be replaced.
7. ETHICS The study protocol, including the Informed Consent Form, was approved by the
local IRB Ethical committee and by the Swiss Medic Authority.
The principal investigator is responsible for informing the IRB or IEC of any amendment
to the protocol in accordance with local requirements.
The study will be performed in accordance with ethical principles of the Declaration of
Helsinki and are consistent with ICH/Good Clinical Practice, and with local regulatory
requirements.
Informed consent: The principal investigator at each centre will ensure that the subject
is given full and adequate oral and written information about the nature, purpose,
possible risk and benefit of the study. Subjects must also be notified that they are
free to discontinue from the study at any time. The subject should be given the
opportunity to ask questions and allowed time to consider the information provided.
No study specific procedures or investigations will be performed before the subject has
signed and dated the informed consent.
The principal investigator(s) will store the original, signed Informed Consent Form. A
copy of the signed Informed Consent Form will be given to the subject.
8. QUALITY CONTROL AND QUALITY ASSURANCE The study will be monitored by a designated
monitor and the investigator will permit trial related audits, IRB/IEC review and
regulatory inspection(s). The investigator will provide direct access to source
data/documents for all quality control activities.
9. PUBLICATION POLICY Two months after study completion, abstracts for congresses and
presentations will be available. Four months after study completion, a first draft of
the manuscript will be available.
10. FINANCING AND INSURANCE Partial financed by AstraZeneca Insurance: Zürich Versicherung
11. PROCEDURES IN CASE OF EMERGENCY, OVERDOSE OR PREGNANCY Procedures in case of medical
emergency: The principal investigator is responsible for ensuring that procedures and
expertise are available to handle medical emergencies during the study. A medical
emergency usually constitutes a SAE and should be reported as such, see Section 4.
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