Optimal Length of Treatment Continuation With Olanzapine After Remission of Manic or Mixed Episode

Study Overview
=================
Brief Summary
-----------------
This is a randomized, parallel, open-label study of patients who have responded to treatment in the acute phase of their manic or mixed episode, with or without psychotic symptoms, with olanzapine in mono or co-therapy, and who are in syndromic and symptomatic remission at the time of enrollment into the study.

Official Title
-----------------
Optimal Treatment Duration With Olanzapine Following Remission of Manic or Mixed Episode. An Open-Label, Randomized Trial Comparing Two Treatment Strategies.

Conditions
-----------------
Bipolar Disorder

Intervention / Treatment
-----------------
* Drug: Olanzapine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Outpatients, male or female, at least 18 years old Patient or legal representative must understand the study and sign an informed consent document before any study procedure Must have a diagnosis of Bipolar Disorder type I and have a recent manic or mixed episode, with or without hospitalization, according to DSM-IV-TR criteria. Patients must be in syndromic and symptomatic remission, following DSM-IV-IR criteria, for the manic or mixed episode, at the time of study entry, with a total score for YMRS less than or equal to 12 and total store for HAMD less than or equal to 8 at visit 1 and 2. Remission must have been achieved taking olanzapine in mono or co-therapy, and it must have been maintained until study entry. Patients must have had, at least, 2 manic or mixed episodes within 3 years of the study entry, taking into account the current one. Exclusion Criteria: Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry, or with a study drug in other clinical trial Patients without symptoms or manic or mixed episode within one month of study entry. Confirmed diagnoses of Schizophrenia or other psychotic disorders (schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, substance-induced or medical condition psychotic disorder, psychotic disorder NOS),following DSM-IV-TR criteria. Patients that have achieved remission with ECT (electro convulsive therapy) in addition to psychopharmacological treatment Drug dependence or abuse, if it is a primary diagnose and the mood disorder is due to his administration Patients that at the time of study entry or at any other time of study, need treatment with antiepileptics or other substances with potential effect as mood stabilizers (i,e new antiepileptics different to Lithium, Valproic Acid and/or Carbamazepine

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Olanzapine|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The main objective of this study is to compare the efficacy in the prevention of relapse to manic, depressive, or |  |  | 
| mixed episodes in two groups of bipolar I patients |  |  | 
| who responded to open-label treatment with olanzapine in mono or co-therapy and who are in symptomatic and syndromic remission at the time of entering the study. |  |  | 
| The first group will receive olanzapine for a period of |  |  | 
| 3 months following inclusion into the study; the second group will receive olanzapine for 12 months. |  |  | 
| Relapses will be evaluated in terms of the total YMRS |  |  | 
| (Young Mania Rating Scale) and HAMD-21 (the 21-item Hamilton Depression Rating Scale) scores. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary objectives posed by this study are the following: |  |  | 
| To compare the efficacy of maintaining olanzapine for 3 months versus maintaining it for 12 months in |  |  | 
| the improvement of symptomatology in patients who had achieved remission. To this end, the reductions |  |  | 
| on the total YMRS score, YMRS specific non-psychotic |  |  | 
| item scores, HAMD 21 total score, the scores on the |  |  | 
| HAMD 21 specific mood-related items, the total and |  |  | 
| positive scores on the BPRS (Brief Psychiatric Rating Scale), and the CGI BP S(Clinical Global Impression of Severity) with respect to baseline will be evaluated. |  |  | 
| DSM IV TR criteria will be used for manic and |  |  | 
| depressive episodes in order to assess syndromic improvement. |  |  | 
| To compare the efficacy of long-term treatments by means of longitudinal assessment using the |  |  | 
| general subscale of the CGI BP M (Clinical Global Impression - Modified) and proceeding to |  |  | 
| intra- and intergroup analyses. |  |  | 
| To evaluate the safety of maintenance treatment |  |  | 
| with olanzapine and other coadjuvant medication |  |  | 
| in both groups of follow up. To collect data |  |  | 
| regarding treatment-derived adverse events, |  |  | 
| changes in vital signs, laboratory analyses, and to measure the severity of possible extrapyramidal symptoms. |  |  | 
| The Simpson Angus Scale, Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale (AIMS) will be used to assess the latter. |  |  | 
| To determine the impact on resource utilization |  |  | 
| the two treatment groups have. Direct costs derived |  |  | 
| from hospital admissions, emergency room visits, |  |  | 
| out-patient visits, home healthcare supports, as well as indirect costs derived from days out of work, |  |  | 
| the patient's economic income, impact on the caregiver will also be quantified. |  |  | 
| To assess the differences between groups |  |  | 
| with respect to improvement in functioning and quality of life. The SF 36 Scale (the 36-Item Social Function Scale) will be applied. |  |  | 
| To understand the degree of impact the illness provokes in relatives or caregivers |  |  | 
| throughout the study. The self-report scale of |  |  | 
| family burden (Escala de Carga Familiar - ECF) will be used for this purpose. |  |  |