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

University Hospital Freiburg

Status and phase: Withdrawn; Phase 3

Conditions: Therapy-resistant Depression

Treatments: Drug: Olanzapine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00273624

Olanzapine Augmentation

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

olanzapine

Experimental group

Description:

10 mg Olanzapine

Treatment:

Drug: Olanzapine

placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo