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”

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Olanzapine
  • 10 mg Olanzapin concurrent to antidepressive medication
• Drug: Placebo
  • placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: olanzapine
  • 10 mg Olanzapine
• Placebo Comparator: placebo
  • Placebo

Primary Measures

• Hamilton-Depression-Scale- HAM-D
  • Time Frame: 14 days
    Safety Issue?: No

Secondary Measures

• rate of remission (HAM-D less or equal 7)
  • Time Frame: 14 days
    Safety Issue?: No
• differences in HAM-D total scores
  • Time Frame: 14 days
    Safety Issue?: No
• differences in MADRS (Montgomery Asberg Depression Rating Scale)and CGI (Clinical Global Impression)scores
  • Time Frame: 14 days
    Safety Issue?: No
• predictive value of HAM-D subscales for treatment response use of comedication
  • Time Frame: 14 days
    Safety Issue?: No
• survival in study
  • Time Frame: 14 days
    Safety Issue?: Yes
• differences in rates of adverse events, weight
  • Time Frame: 14 days
    Safety Issue?: Yes
• differences in HAM-D scores and survival in extension phase
  • Time Frame: 2 months
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University Hospital Freiburg Other

Overall Clinical Trial Officials and Contacts

Claus Normann, MD Principal Investigator Department of Psychiatry, University of Freiburg  

Overall Contact: Claus Normann, MD ++497612706634 claus.normann@uniklinik-freiburg.de

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00273624

Study ID Number: Olanzapine Augmentation

ClinicalTrials.gov Identifier: NCT00273624

Health Authority: Germany: Federal Institute for Drugs and Medical Devices