Olanzapine Augmentation Therapy in Treatment-resistant Depression: a Double-blind Placebo-controlled Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Olanzapine Augmentation Therapy in Treatment-resistant Depression: a Double-blind Placebo-controlled Trial

Conditions
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Therapy-resistant Depression

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: olanzapine<br>10 mg Olanzapine | Drug: Olanzapine<br>* 10 mg Olanzapin concurrent to antidepressive medication<br>* Other names: Zyprexa;|
| Placebo Comparator: placebo<br>Placebo | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton-Depression-Scale- HAM-D |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of remission (HAM-D less or equal 7) |  | 14 days | 
| differences in HAM-D total scores |  | 14 days | 
| differences in MADRS (Montgomery Asberg Depression Rating Scale)and CGI (Clinical Global Impression)scores |  | 14 days | 
| predictive value of HAM-D subscales for treatment response use of comedication |  | 14 days | 
| survival in study |  | 14 days | 
| differences in rates of adverse events, weight |  | 14 days | 
| differences in HAM-D scores and survival in extension phase |  | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Therapy-resistant depression, add-on therapy depression