Clinical trial NCT00273624: Olanzapine Augmentation Therapy in Treatment-resistant Depression: a Double-blind Placebo-controlled Trial
Official title: Olanzapine Augmentation Therapy in Treatment-resistant Depression: a Double-blind Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Therapy-resistant Depression
Keywords: Therapy-resistant depression
add-on therapy depression
Lead sponsor: University Hospital Freiburg
Sponsor class: OTHER
First posted: 2006-01-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 60 patients with major depression will be treated with 10 mg Olanzapine or Placebo for 2 weeks. In case of response (reduction of depressive symptoms)the study will be continued for further 60 days.

Detailed description: The study is using a randomized double-blind, parallel-group, placebo-controlled design. 30 patients per treatment group will be included into the study and randomized to the treatment groups using a computer program. Psychotic features of depression will be excluded by a score of 2 or less in the PANSS subscales P1, P3 and P6. Treatment resistance as defined by history of non-response to two antidepressants from different classes at an acceptable dose and period is confirmed retrospectively. If possible, treatment compliance should be confirmed by plasma level examination. After informed consent, visit 1 is performed on day 0 (inclusion criteria, history, demographics, physical examination, vital signs, HAMD, MADRS, CGI, lab). Study medication is started on day 1, the antidepressive therapy is continued at stable dose until the end of the study. Patients will receive a double-blind therapy of either 10 mg/d olanzapine or placebo. Study visits will be performed on days 4, 7, and 14 (visits 2-4: vital signs, HAMD, MADRS, CGI, lab).

After 14 days, the patients will be classified as responders or non-responders. A responder is defined by a reduction of the initial HAM-D score of more than 50%. Study treatment will be stopped in non-responders and continued in a double-blind manner in responders for further 60 days. Thereafter, the the study medication is stopped and the patients are observed for further 14 days. Study visits will be performed every 14 days. This extension phase was added to examine if a prolonged treatment with olanzapine could ensure a sustained treatment effect. It should be excluded that olanzapine has a short-term tranquillizer-like effect or leads to unfavourable medium- to-long-term depressiogenic effects as observed with other neuroleptics used in depression ( e.g. fluspirilene). Moreover, withdrawal effects should be excluded.

Eligibility criteria: Inclusion Criteria:

* major depression without psychotic features
* therapy resistance (2 courses of antidepressants from different classes for more than 3 weeks in adequate dose
* HAM-D score greater/equal than 17
* age 18-65

Exclusion Criteria:

* bipolar disorder
* active alcohol or illicit drug use
* female with ineffective contraception
* severe medical conditions, epilepsy
* psychotic features

Primary outcomes:
measure: Hamilton-Depression-Scale- HAM-D
timeFrame: 14 days
Secondary outcomes:
measure: rate of remission (HAM-D less or equal 7)
timeFrame: 14 days
measure: differences in HAM-D total scores
timeFrame: 14 days
measure: differences in MADRS (Montgomery Asberg Depression Rating Scale)and CGI (Clinical Global Impression)scores
timeFrame: 14 days
measure: predictive value of HAM-D subscales for treatment response use of comedication
timeFrame: 14 days
measure: survival in study
timeFrame: 14 days
measure: differences in rates of adverse events, weight
timeFrame: 14 days
measure: differences in HAM-D scores and survival in extension phase
timeFrame: 2 months
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Dept. of Psychiatry, University of Freiburg
Study officials:
affiliation: Department of Psychiatry, University of Freiburg
name: Claus Normann, MD
role: PRINCIPAL_INVESTIGATOR
References: