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.

Study Overview

• Status: Withdrawn
• Conditions: Therapy-resistant Depression
• Intervention / Treatment: Drug: Placebo; Drug: Olanzapine

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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Freiburg, Germany, 79104
    • Dept. of Psychiatry, University of Freiburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; Placebo	Drug: Placebo; placebo
Experimental: olanzapine; 10 mg Olanzapine	Drug: Olanzapine; 10 mg Olanzapin concurrent to antidepressive medication; Other Names: Zyprexa

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University Hospital Freiburg
• Investigators: Principal Investigator: Claus Normann, MD, Department of Psychiatry, University of Freiburg

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: January 4, 2006
• First Submitted That Met QC Criteria: January 4, 2006
• First Posted (Estimate): January 9, 2006

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: add-on therapy depression; Therapy-resistant depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Olanzapine
• Other Study ID Numbers: Olanzapine Augmentation