Trial Outcomes & Findings for Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders (NCT NCT00001656)

NCT ID: NCT00001656

Last Updated: 2011-04-12

Results Overview

Measures change in affective flattening or blunting, alogia, avolition/apathy, anhedonia/asociality, attention; minimum score = 0; maximum score = 125; lower values are considered a better outcome

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 25 participants
• Primary outcome timeframe: 8 week double-blind study period; baseline and 8 weeks
• Results posted on: 2011-04-12

Participant Flow

Participant milestones

Measure	Olanzapine Group All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Overall Study STARTED	13	12
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders

Baseline characteristics by cohort

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Total n=25 Participants Total of all reporting groups
Age, Categorical <=18 years	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	12.8 years STANDARD_DEVIATION 2.4 • n=5 Participants	11.7 years STANDARD_DEVIATION 2.3 • n=7 Participants	12.2 years STANDARD_DEVIATION 2.1 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	12 participants n=7 Participants	25 participants n=5 Participants

PRIMARY outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

Measures change in affective flattening or blunting, alogia, avolition/apathy, anhedonia/asociality, attention; minimum score = 0; maximum score = 125; lower values are considered a better outcome

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in the Scale for the Assessment of Negative Symptoms	-14 Scores on a scale Interval -20.0 to -7.0	-25 Scores on a scale Interval -34.0 to -15.0

PRIMARY outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

Measures change in the severity of symptoms; Minimum score = 1; maximum score = 7; lower score is considered a better outcome.

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in the Clinical Global Impression Severity of Symptoms Scale	-0.6 Scores on a scale Interval -1.3 to 0.1	-1.6 Scores on a scale Interval -2.3 to -0.8

PRIMARY outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

A 24-item scale measuring change in interpersonal behaviors, mood, psychosis, anxiety, speech, sleep, orientation and physical activity. Lowest score = 24; highest score = 168; lower score is considered a better outcome.

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in the Brief Psychiatric Rating Scale-24	-13 Scores on a scale Interval -21.0 to -6.0	-19 Scores on a scale Interval -26.0 to -12.0

PRIMARY outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

Measures change in hallucinations, delusions, bizarre behavior, and thought organization. Minimum score = 0; maximum score = 170; lower score is considered a better outcome.

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in the Scale for the Assessment of Positive Symptoms	-7 Scores on a scale Interval -18.0 to 5.0	-21 Scores on a scale Interval -33.0 to -9.0

PRIMARY outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

Measures change in psychosis severity; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in the Bunney-Hamburg Rating Scale for Psychosis	-3.1 Scores on a scale Interval -5.0 to -1.2	-4 Scores on a scale Interval -5.3 to -2.7

PRIMARY outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

Measures change in severity of depression; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in Bunney-Hamburg Rating Scale for Depression	0.4 Scores on a scale Interval -0.6 to 1.4	0.2 Scores on a scale Interval -0.5 to 0.8

PRIMARY outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

Measures change in the severity of mania; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in Bunney-Hamburg Rating Scale for Mania	-0.4 Scores on a scale Interval -2.3 to 1.5	-0.8 Scores on a scale Interval -1.7 to 0.1

PRIMARY outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

Measures change in the severity of anxiety; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in the Bunney-Hamburg Rating Scale for Anxiety	-0.5 Scores on a scale Interval -1.6 to 0.5	0.6 Scores on a scale Interval -2.3 to 1.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in Weight	3.6 kilograms Standard Deviation 4.0	3.8 kilograms Standard Deviation 6.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

BMI is calculated by the following formula: weight (in kilograms) divided by the square of the height (in meters)

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in Body Mass Index (BMI)	1.4 kg/m² Standard Deviation 1.6	1.6 kg/m² Standard Deviation 2.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

minimum score = 10; maximum score = 50; lower score is considered a more favorable outcome

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in Extrapyramidal Movements as Measured by the Abnormal Involuntary Movements Scale (AIMS)	0 scores on a scale Interval -9.0 to 4.0	0 scores on a scale Interval -4.0 to 8.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 week double-blind study period; baseline and 8 weeks

minimum score = 10; maximum score = 90; lower score considered a more favorable outcome

Outcome measures

Measure	Olanzapine Group n=13 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 Participants All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Change in Extrapyramidal Movements as Measured by the Simpson Angus Scale Score	0 scores on a scale Interval -2.0 to 1.0	0 scores on a scale Interval -3.0 to 1.0

Adverse Events

Olanzapine Group

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Clozapine Group

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Olanzapine Group n=13 participants at risk All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 participants at risk All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Blood and lymphatic system disorders Abnormal white blood count	7.7% 1/13 • Number of events 1 • 8 week-double-blind study period All adverse side effects are reported.	16.7% 2/12 • Number of events 2 • 8 week-double-blind study period All adverse side effects are reported.

Other adverse events

Measure	Olanzapine Group n=13 participants at risk All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.	Clozapine Group n=12 participants at risk All medications were given by mouth, in identical tablet form. Day 1, patient was given 5mg olanzapine or 12.5mg clozapine. Clozapine dose was then increased every other day, the first increase by 12.5mg (to a total dose of 25mg/day) and then in steps of 25mg. When the clozapine dose reached 150mg/day, the olanzapine dose was increased to 10mg/day. When the clozapine dose reached 300mg/day, the olanzapine dose was increased to 15mg/day. Further increases were guided by clinical judgment to a maximum of 20mg/day of olanzapine and 900mg/day of clozapine.
Renal and urinary disorders Enuresis	7.7% 1/13 • Number of events 1 • 8 week-double-blind study period All adverse side effects are reported.	41.7% 5/12 • Number of events 5 • 8 week-double-blind study period All adverse side effects are reported.
Metabolism and nutrition disorders Increased appetite	30.8% 4/13 • Number of events 4 • 8 week-double-blind study period All adverse side effects are reported.	33.3% 4/12 • Number of events 4 • 8 week-double-blind study period All adverse side effects are reported.
Gastrointestinal disorders Hypersalivation	30.8% 4/13 • Number of events 4 • 8 week-double-blind study period All adverse side effects are reported.	66.7% 8/12 • Number of events 8 • 8 week-double-blind study period All adverse side effects are reported.
Gastrointestinal disorders Constipation	15.4% 2/13 • Number of events 2 • 8 week-double-blind study period All adverse side effects are reported.	16.7% 2/12 • Number of events 2 • 8 week-double-blind study period All adverse side effects are reported.
Nervous system disorders Difficulty concentrating	7.7% 1/13 • Number of events 1 • 8 week-double-blind study period All adverse side effects are reported.	33.3% 4/12 • Number of events 4 • 8 week-double-blind study period All adverse side effects are reported.
Nervous system disorders Somnolence	15.4% 2/13 • Number of events 2 • 8 week-double-blind study period All adverse side effects are reported.	16.7% 2/12 • Number of events 2 • 8 week-double-blind study period All adverse side effects are reported.
Nervous system disorders Insomnia	7.7% 1/13 • Number of events 1 • 8 week-double-blind study period All adverse side effects are reported.	25.0% 3/12 • Number of events 3 • 8 week-double-blind study period All adverse side effects are reported.
Cardiac disorders Hypertension	9.1% 1/11 • Number of events 1 • 8 week-double-blind study period All adverse side effects are reported.	63.6% 7/11 • Number of events 7 • 8 week-double-blind study period All adverse side effects are reported.
Cardiac disorders tachycardia >100 beats/min (supine)	16.7% 2/12 • Number of events 2 • 8 week-double-blind study period All adverse side effects are reported.	70.0% 7/10 • Number of events 7 • 8 week-double-blind study period All adverse side effects are reported.
Cardiac disorders Tachycardia >120 beats/min (supine)	0.00% 0/12 • 8 week-double-blind study period All adverse side effects are reported.	10.0% 1/10 • Number of events 1 • 8 week-double-blind study period All adverse side effects are reported.

Additional Information

Judith L. Rapoport, M.D.

National Institute of Mental Health

Phone: 301-496-6080

Email: rapoporj@mail.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place