A Study in the Treatment of Acute Mania

Study Overview
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Brief Summary
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The purpose of this study is to test the efficacy and total costs of olanzapine versus commonly used conventional antipsychotics in Sweden.

Detailed Description
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The primary objective is to show that the efficacy of olanzapine is non-inferior to the conventional antipsychotics haloperidol or zuclopentixol in the treatment of an acute manic or mixed episode of bipolar disorder. Efficacy is defined as time to remission, as measured by the total scores of the Young Mania Rating Scale (Y-MRS), MADRS-S, and Clinical Global Impression - Bipolar (CGI-BP). Time from baseline to remission is defined as the primary efficacy measure. Remission is defined as a Y-MRS score <=12 AND a MADRS-S score <=12 AND CGI-BP = 1 or 2. Secondary efficacy assessments will include time from baseline to Response, as defined as a reduction of Y-MRS score greater than or equal to 50% compared to baseline Relapse of mania, as defined as a Y-MRS score >= 16 AND CGI-BP >2 after having met the criteria for remission Switch into depression, as defined as a MADRS-S score >=17 AND fulfilled criteria for Major Depression as self-assessed by DSRS.

Official Title
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A Randomized Open Label Study on the Efficacy, Tolerability, and Total Costs of Olanzapine Versus Conventional Antipsychotics in the Treatment of Acute Mania in Sweden

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: olanzapine
* Drug: haloperidol
* Drug: zuclopentixol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of bipolar I disorder and currently display an acute manic or mixed episode (with or without psychotic features) Patients must have a Y-MRS total score of greater or equal to 20 at visit 2 Patients must have experienced at least one manic or mixed episode prior to study enrollment Female of childbearing potential must be using a medically accepted means of contraception, or practice sexual abstinence Each patient must have a level of understanding sufficient to communicate intelligently with study personnel Patients must be considered reliable Each patient must understand the nature of the study and signed informed consent Exclusion Criteria: Female patients who are pregnant or lactating Serious, unstable illnesses such that hospitalization for the disease is anticipated within 3 month or death is anticipated within 3 years Uncorrected hypothyroidism or hyperthyroidism Narrow-angle glaucoma History of allergic reactions or intolerance to study medications DSM-IV substance dependence within the past 30 days at the judgement of the investigator Judged clinically to be at serious suicidal risk Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to visit 2 Any patient treated with clozapine within 4 weeks prior to visit 2 Subjects who have received treatment with ECT within one month prior to visit 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Patients will be given olanzapine | Drug: olanzapine<br>* physician determined dose, oral, daily, 5 months<br>* Other names: Zyprexa;|
| Active Comparator: B<br>Patients will be given either haloperidol or zuclopentixol | Drug: haloperidol<br>* physician determined dose, oral, parenteral (<= 3 days), daily, 5 months<br>Drug: zuclopentixol<br>* physician determined dose, oral, parenteral (<= 3 days), daily, 5 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to remission by Young Mania Rating Scale, MADRS-S and CGI-BP |  | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resource utilization Clinical Report Form (RUCRF) |  | 5 months | 
| Disability free day assessment (DFDA) |  | 5 months | 
| Medication compliance |  | 5 months | 
| Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) |  | 5 months | 
| Euro Qol instrument |  | 5 months | 
| Drug Attitude Inventory (DAI) |  | 5 months | 
| Response by Y-MRS |  | 5 months | 
| Frequency of and time to relapse into mania by Y-MRS and CGI-BP |  | 5 months | 
| Frequency of and time to switch to depression by MADRS-S and DSRS |  | 5 months | 
| Time to remission in patients with psychotic features by SCID-I judgement, Y-MRS item 8 and PANSS positive items mean sum |  | 5 months | 
| Adverse events |  | 5 months |