Bipolar Disorder
Conditions
Keywords
Manic or mixed episode associated with bipolar I disorder
Brief summary
The purpose of this study is to confirm the efficacy of olanzapine in the treatment of manic or mixed symptoms associated with bipolar I disorder.
Interventions
DRUGolanzapine
5-20 mg, oral, once daily (evening), for 6 weeks
DRUGhaloperidol
2.5-10 mg, oral, twice daily (morning and evening), for 6 weeks.
DRUGplacebo
placebo, oral tablets, twice daily (morning and evening), for 3 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Meet the criteria for manic or mixed episodes according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) and have a diagnosis of 294.4x Bipolar I Disorder, Most Recent Episode Manic or 296.6x Bipolar I Disorder, Most Recent Episode Mixed. * Have a total score on the Young Mania Rating Scale (YMRS) of at least 20 at Visit 1 and Visit 2.
Exclusion criteria
* Have received an antidepressant or a psychostimulant within 5 days prior to Visit 1. * The duration of the current episode is more than 90 days at Visit 1. * Have a history or a diagnosis of diabetes mellitus. * Have received any psychotropic medication within 2 days prior to Visit 2 (except for benzodiazepines).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score | Baseline, 3 weeks | The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol) | 6 weeks | Remission of bipolar disorder was defined as completing the 6-week period with meeting the criteria for Young Mania Rating Scale (YMRS) total score of 12 or less and 17-Item Hamilton Depression Rating Scale (HAMD-17) total scores of 7 or less at Week 6. YMRS is an 11-item scale measuring severity of manic episodes; total score ranges = 0 (normal) to 60 (severe). The 17-item HAMD measures depression severity; total score ranges = 0 (normal) to 52 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100. |
| Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness | Baseline, 6 weeks | A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of overall mood symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients). |
| Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale | Baseline, 3 weeks, 6 weeks | A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of manic symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients). |
| Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks | Baseline, 3 weeks, 6 weeks | Participants who had 50 percent or more decrease from the baseline in YMRS total scores were defined as a responder. The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. Response Rate (percent) = number of patients meeting response criterion for manic symptom divided by number of patients in treatment arm, multiplied by 100. |
| Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS) | Baseline, 6 weeks | The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. |
| Percentage of Participants Who Switched to Symptomatic Depression | 3 weeks, 6 weeks | Switch to symptomatic depression was defined as HAMD-17 total score ≥13 at any time in the participants with HAMD-17 total scores ≤7 at baseline. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). |
| Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) | Baseline, 3 weeks, 6 weeks | Assesses positive symptoms associated with schizophrenia. 7 items make up the Positive scale (ex. delusions, conceptual disorganization, and hallucinatory behavior). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total Positive Subscale scores range from 7 to 49. For this study, the score was converted to 0 to 6 for each item range; hence, the total positive subscale score ranges from 0 to 42. |
| Percentage of Participants Who Switched to Syndromic Depression | 3 weeks, 6 weeks | Switch to syndromic depression was operationally defined by meeting both of the following criteria: At baseline, the symptoms did not meet the criteria for a mixed episode based on the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). The critiera were met for a Major Depressive Episode (MDE), at any point after randomization, based on DSM-IV-TR. Rather than the 2-week period required for an MDE in the DSM-IV-TR, the patient had to meet the criteria of an MDE for at least 7 consecutive days (during Weeks 1 through 6). |
| Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score | Baseline to 6 weeks | Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the sum of the 8 item scores, for a total range of 0 (normal) to 32 (severe). |
| Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 3 weeks, 6 weeks | Participants who had a YMRS total score of 12 or less were considered to be in remission of manic symptoms. YMRS is an 11-item scale that measures severity of manic episodes; total score ranges from 0 (normal) to 60 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100. |
Countries
Japan
Participant flow
Pre-assignment details
Study Period I was a week-long Screening Period. Study Period II was a 3-week-long Early Double-Blind Period. Study Period III was a 3-week-long Last Double-Blind Period.
Participants by arm
| Arm | Count |
|---|---|
| Olanzapine olanzapine: 5 to 20 mg per day for 6 weeks | 104 |
| Haloperidol haloperidol: 2.5 to 10 mg per day for 6 weeks | 20 |
| Placebo placebo for 3 weeks, then olanzapine 5 to 20 mg per day for 3 weeks | 97 |
| Total | 221 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Study Period II | Adverse Event | 9 | 5 | 7 |
| Study Period II | Entry Criteria Not Met | 2 | 0 | 2 |
| Study Period II | Lack of Efficacy | 15 | 1 | 28 |
| Study Period II | Physician Decision | 0 | 1 | 0 |
| Study Period II | Protocol Violation | 4 | 2 | 1 |
| Study Period II | Reason Not Specified | 2 | 0 | 5 |
| Study Period II | Withdrawal by Subject | 1 | 3 | 4 |
| Study Period III | Adverse Event | 1 | 0 | 3 |
| Study Period III | Protocol Violation | 1 | 1 | 2 |
| Study Period III | Reason Not Specified | 9 | 0 | 2 |
| Study Period III | Sponsor Decision | 1 | 0 | 0 |
| Study Period III | Withdrawal by Subject | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Olanzapine | Haloperidol | Placebo | Total |
|---|---|---|---|---|
| 17-Item Hamilton Depression Rating Scale Total Score | 4.5 units on a scale STANDARD_DEVIATION 3.9 | 4.1 units on a scale STANDARD_DEVIATION 3.7 | 4.9 units on a scale STANDARD_DEVIATION 4.5 | 4.7 units on a scale STANDARD_DEVIATION 4.1 |
| Age Continuous | 43.1 years STANDARD_DEVIATION 12 | 49.3 years STANDARD_DEVIATION 11.9 | 42.5 years STANDARD_DEVIATION 10.9 | 43.4 years STANDARD_DEVIATION 11.6 |
| Age of Onset of Illness | 31.2 years STANDARD_DEVIATION 11.6 | 37.7 years STANDARD_DEVIATION 12.5 | 30.9 years STANDARD_DEVIATION 10.7 | 31.6 years STANDARD_DEVIATION 11.4 |
| Clinical Global Impression-Severity of Illness, Bipolar Version (CGI-BP) Depression | 1.3 units on a scale STANDARD_DEVIATION 0.6 | 1.1 units on a scale STANDARD_DEVIATION 0.2 | 1.3 units on a scale STANDARD_DEVIATION 0.7 | 1.2 units on a scale STANDARD_DEVIATION 0.6 |
| Clinical Global Impression-Severity of Illness, Bipolar Version (CGI-BP) Mania | 4.2 units on a scale STANDARD_DEVIATION 1 | 4.6 units on a scale STANDARD_DEVIATION 0.8 | 4.1 units on a scale STANDARD_DEVIATION 1.1 | 4.2 units on a scale STANDARD_DEVIATION 1 |
| Clinical Global Impression-Severity of Illness, Bipolar Version (CGI-BP) Overall Mood | 4.1 units on a scale STANDARD_DEVIATION 1 | 4.4 units on a scale STANDARD_DEVIATION 1.2 | 4.1 units on a scale STANDARD_DEVIATION 1.1 | 4.1 units on a scale STANDARD_DEVIATION 1.1 |
| Current Illness Episode: Manic versus Mixed Manic | 95 participants | 19 participants | 89 participants | 203 participants |
| Current Illness Episode: Manic versus Mixed Mixed | 9 participants | 1 participants | 8 participants | 18 participants |
| Current Illness Episode: Psychotic versus Nonpsychotic Nonpsychotic | 87 participants | 16 participants | 78 participants | 181 participants |
| Current Illness Episode: Psychotic versus Nonpsychotic Psychotic | 17 participants | 4 participants | 19 participants | 40 participants |
| Height | 162.74 centimeters (cm) STANDARD_DEVIATION 8.07 | 162.10 centimeters (cm) STANDARD_DEVIATION 7.87 | 163.09 centimeters (cm) STANDARD_DEVIATION 9.66 | 162.84 centimeters (cm) STANDARD_DEVIATION 8.76 |
| Hospitalization Status In-Patients | 41 participants | 10 participants | 38 participants | 89 participants |
| Hospitalization Status Out-Patients | 63 participants | 10 participants | 59 participants | 132 participants |
| Length of Current Illness Episode | 34.6 days STANDARD_DEVIATION 22.9 | 34.2 days STANDARD_DEVIATION 22 | 33.5 days STANDARD_DEVIATION 25.4 | 34.1 days STANDARD_DEVIATION 23.9 |
| Positive and Negative Syndrome Scale Positive Subscale Score | 11.5 units on a scale STANDARD_DEVIATION 4.8 | 11.3 units on a scale STANDARD_DEVIATION 4.5 | 10.7 units on a scale STANDARD_DEVIATION 4.7 | 11.1 units on a scale STANDARD_DEVIATION 4.7 |
| Psychosis Mood-Congruent | 16 participants | 4 participants | 19 participants | 39 participants |
| Psychosis Mood-Incongruent | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Japanese | 104 participants | 20 participants | 97 participants | 221 participants |
| Region of Enrollment Japan | 104 participants | 20 participants | 97 participants | 221 participants |
| Sex: Female, Male Female | 55 Participants | 9 Participants | 57 Participants | 121 Participants |
| Sex: Female, Male Male | 49 Participants | 11 Participants | 40 Participants | 100 Participants |
| Weight | 60.88 kilograms (kg) STANDARD_DEVIATION 11.69 | 59.20 kilograms (kg) STANDARD_DEVIATION 9.87 | 61.86 kilograms (kg) STANDARD_DEVIATION 13.78 | 61.17 kilograms (kg) STANDARD_DEVIATION 12.49 |
| Young Mania Rating Scale (YMRS) Total Score | 27.7 units on a scale STANDARD_DEVIATION 5.9 | 26.6 units on a scale STANDARD_DEVIATION 4.5 | 26.9 units on a scale STANDARD_DEVIATION 5.6 | 27.3 units on a scale STANDARD_DEVIATION 5.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 78 / 105 | 14 / 20 | 64 / 96 |
| serious Total, serious adverse events | 1 / 105 | 0 / 20 | 3 / 96 |
Outcome results
Primary
Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score
The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.
Time frame: Baseline, 3 weeks
Population: Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score | -12.6 units on a scale | Standard Deviation 10 |
| Haloperidol | Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score | -14.3 units on a scale | Standard Deviation 11.4 |
| Placebo | Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score | -6.8 units on a scale | Standard Deviation 14 |
p-value: <0.00195% CI: [-8.87, -2.37]ANCOVA
Secondary
Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale
A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of manic symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Time frame: Baseline, 3 weeks, 6 weeks
Population: Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale | 3-Week Change | -1.2 units on a scale | Standard Deviation 1.2 |
| Olanzapine | Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale | 6-Week Change | -1.7 units on a scale | Standard Deviation 1.5 |
| Haloperidol | Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale | 3-Week Change | -1.7 units on a scale | Standard Deviation 1.7 |
| Haloperidol | Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale | 6-Week Change | -1.9 units on a scale | Standard Deviation 1.9 |
| Placebo | Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale | 3-Week Change | -0.6 units on a scale | Standard Deviation 1.5 |
| Placebo | Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale | 6-Week Change | -1.0 units on a scale | Standard Deviation 1.7 |
p-value: 0.00695% CI: [-0.87, -0.15]ANCOVA
p-value: 0.72295% CI: [-0.82, 0.57]ANCOVA
Secondary
Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS)
Assesses positive symptoms associated with schizophrenia. 7 items make up the Positive scale (ex. delusions, conceptual disorganization, and hallucinatory behavior). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total Positive Subscale scores range from 7 to 49. For this study, the score was converted to 0 to 6 for each item range; hence, the total positive subscale score ranges from 0 to 42.
Time frame: Baseline, 3 weeks, 6 weeks
Population: Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) | 3-Week Change | -1.8 units on a scale | Standard Deviation 4.1 |
| Olanzapine | Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) | 6-Week Change | -2.2 units on a scale | Standard Deviation 4.4 |
| Haloperidol | Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) | 3-Week Change | -1.8 units on a scale | Standard Deviation 4.3 |
| Haloperidol | Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) | 6-Week Change | -1.6 units on a scale | Standard Deviation 4.3 |
| Placebo | Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) | 3-Week Change | -0.0 units on a scale | Standard Deviation 5.3 |
| Placebo | Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS) | 6-Week Change | -0.3 units on a scale | Standard Deviation 5.7 |
p-value: 0.01995% CI: [-2.71, -0.25]ANCOVA
p-value: 0.85595% CI: [-1.95, 1.62]ANCOVA
Secondary
Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness
A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of overall mood symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Time frame: Baseline, 6 weeks
Population: Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness | -1.6 units on a scale | Standard Deviation 1.5 |
| Haloperidol | Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness | -1.3 units on a scale | Standard Deviation 1.8 |
| Placebo | Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness | -0.9 units on a scale | Standard Deviation 1.7 |
p-value: 0.17195% CI: [-1.15, 0.21]ANCOVA
Secondary
Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS)
The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.
Time frame: Baseline, 6 weeks
Population: Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olanzapine | Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS) | -16.0 units on a scale | Standard Deviation 11.4 |
| Haloperidol | Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS) | -14.7 units on a scale | Standard Deviation 13.1 |
| Placebo | Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS) | -10.1 units on a scale | Standard Deviation 15.8 |
p-value: 0.77495% CI: [-6.15, 4.59]ANCOVA
Secondary
Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score
Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the sum of the 8 item scores, for a total range of 0 (normal) to 32 (severe).
Time frame: Baseline to 6 weeks
Population: Participants in the Safety Analysis Set (participants who had baseline and post-baseline measurements). Participants were included in the treatment group for which they actually received treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olanzapine | Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score | Baseline | 0.20 units on a scale | Standard Deviation 0.66 |
| Olanzapine | Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score | Maximum Change from Baseline | 0.70 units on a scale | Standard Deviation 1.51 |
| Haloperidol | Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score | Baseline | 0.50 units on a scale | Standard Deviation 1.19 |
| Haloperidol | Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score | Maximum Change from Baseline | 2.70 units on a scale | Standard Deviation 2.89 |
| Placebo | Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score | Baseline | 0.30 units on a scale | Standard Deviation 0.91 |
| Placebo | Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score | Maximum Change from Baseline | 0.09 units on a scale | Standard Deviation 1.09 |
p-value: 0.003Wilcoxon Rank Sum
Secondary
Percentage of Participants Who Switched to Symptomatic Depression
Switch to symptomatic depression was defined as HAMD-17 total score ≥13 at any time in the participants with HAMD-17 total scores ≤7 at baseline. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Time frame: 3 weeks, 6 weeks
Population: Participants in the Full Analysis Set (participants who had baseline and post-baseline measurement) who had HAMD-17 total scores ≤7 at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Percentage of Participants Who Switched to Symptomatic Depression | 3-Week Symptomatic Depression Rate | 2.4 percentage of participants |
| Olanzapine | Percentage of Participants Who Switched to Symptomatic Depression | 6-Week Symptomatic Depression Rate | 2.4 percentage of participants |
| Haloperidol | Percentage of Participants Who Switched to Symptomatic Depression | 3-Week Symptomatic Depression Rate | 16.7 percentage of participants |
| Haloperidol | Percentage of Participants Who Switched to Symptomatic Depression | 6-Week Symptomatic Depression Rate | 16.7 percentage of participants |
| Placebo | Percentage of Participants Who Switched to Symptomatic Depression | 3-Week Symptomatic Depression Rate | 1.3 percentage of participants |
| Placebo | Percentage of Participants Who Switched to Symptomatic Depression | 6-Week Symptomatic Depression Rate | 2.7 percentage of participants |
p-value: 0.69895% CI: [-3.2, 4.9]Cochran-Mantel-Haenszel
p-value: 0.01495% CI: [-31.7, 3.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Switched to Syndromic Depression
Switch to syndromic depression was operationally defined by meeting both of the following criteria: At baseline, the symptoms did not meet the criteria for a mixed episode based on the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). The critiera were met for a Major Depressive Episode (MDE), at any point after randomization, based on DSM-IV-TR. Rather than the 2-week period required for an MDE in the DSM-IV-TR, the patient had to meet the criteria of an MDE for at least 7 consecutive days (during Weeks 1 through 6).
Time frame: 3 weeks, 6 weeks
Population: Participants in the Full Analysis Set (participants who had baseline and post-baseline measurement) who had manic (not mixed) episode at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Percentage of Participants Who Switched to Syndromic Depression | 3-Week Syndromic Depression Rate | 0.0 percentage of participants |
| Olanzapine | Percentage of Participants Who Switched to Syndromic Depression | 6-Week Syndromic Depression Rate | 1.1 percentage of participants |
| Haloperidol | Percentage of Participants Who Switched to Syndromic Depression | 3-Week Syndromic Depression Rate | 5.3 percentage of participants |
| Haloperidol | Percentage of Participants Who Switched to Syndromic Depression | 6-Week Syndromic Depression Rate | 5.3 percentage of participants |
| Placebo | Percentage of Participants Who Switched to Syndromic Depression | 3-Week Syndromic Depression Rate | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Switched to Syndromic Depression | 6-Week Syndromic Depression Rate | 0.0 percentage of participants |
p-value: 0.13695% CI: [-14.9, 5.7]Cochran-Mantel-Haenszel
Secondary
Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol)
Remission of bipolar disorder was defined as completing the 6-week period with meeting the criteria for Young Mania Rating Scale (YMRS) total score of 12 or less and 17-Item Hamilton Depression Rating Scale (HAMD-17) total scores of 7 or less at Week 6. YMRS is an 11-item scale measuring severity of manic episodes; total score ranges = 0 (normal) to 60 (severe). The 17-item HAMD measures depression severity; total score ranges = 0 (normal) to 52 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100.
Time frame: 6 weeks
Population: Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olanzapine | Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol) | 44.2 percentage of participants |
| Haloperidol | Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol) | 20.0 percentage of participants |
p-value: 0.06495% CI: [1.6, 40.4]Cochran-Mantel-Haenszel
Secondary
Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks
Participants who had a YMRS total score of 12 or less were considered to be in remission of manic symptoms. YMRS is an 11-item scale that measures severity of manic episodes; total score ranges from 0 (normal) to 60 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100.
Time frame: 3 weeks, 6 weeks
Population: Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 3-Week Remission Rate | 47.1 percentage of participants |
| Olanzapine | Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 6-Week Remission Rate | 63.5 percentage of participants |
| Haloperidol | Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 3-Week Remission Rate | 65.0 percentage of participants |
| Haloperidol | Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 6-Week Remission Rate | 60.0 percentage of participants |
| Placebo | Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 3-Week Remission Rate | 41.2 percentage of participants |
| Placebo | Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 6-Week Remission Rate | 52.6 percentage of participants |
p-value: 0.38495% CI: [-7.3, 19.2]Cochran-Mantel-Haenszel
p-value: 0.98295% CI: [-21.3, 21.8]Cochran-Mantel-Haenszel
Secondary
Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks
Participants who had 50 percent or more decrease from the baseline in YMRS total scores were defined as a responder. The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. Response Rate (percent) = number of patients meeting response criterion for manic symptom divided by number of patients in treatment arm, multiplied by 100.
Time frame: Baseline, 3 weeks, 6 weeks
Population: Participants in the Full Analysis Set: participants who had baseline and post-baseline measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olanzapine | Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 3 Week Response Rate | 51.0 percentage of participants |
| Olanzapine | Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 6 Week Response Rate | 67.3 percentage of participants |
| Haloperidol | Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 6 Week Response Rate | 65.0 percentage of participants |
| Haloperidol | Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 3 Week Response Rate | 65.0 percentage of participants |
| Placebo | Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 3 Week Response Rate | 44.3 percentage of participants |
| Placebo | Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks | 6 Week Response Rate | 55.7 percentage of participants |
p-value: 0.33395% CI: [-6.7, 20.1]Cochran-Mantel-Haenszel
p-value: 0.90895% CI: [-21, 18.4]Cochran-Mantel-Haenszel