Trial Outcomes & Findings for Quetiapine SR and Divalproex Sodium ER in the Treatment of Anxiety in Bipolar Disorder With Panic Disorder and/or GAD (NCT NCT00579280)

NCT ID: NCT00579280

Last Updated: 2020-06-11

Results Overview

The CGI-21 Anxiety is a 21-point clinician-rated global improvement for anxiety symptoms. Response range: -10 to +10. The higher the score the more improvement. At Baseline all patients have a score of "0" (zero), against which any subsequent improvements or deterioration is assessed. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA). The focus was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANOVA. Outcomes showing scores above zero indicate that patients did better, i.e. showed improvement on this scale.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 224 participants
• Primary outcome timeframe: 8 weeks (using LOCF Repeated Measures ANOVA)
• Results posted on: 2020-06-11

Participant Flow

Participant milestones

Measure	Quetiapine SR Quetiapine SR (sustained release)	Divalproex Sodium ER Divalproex Sodium ER (extended release)	Placebo Placebo control
Overall Study STARTED	49	49	51
Overall Study COMPLETED	47	46	51
Overall Study NOT COMPLETED	2	3	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

This scale was only administered to the last 74 patients in the trial

Baseline characteristics by cohort

Measure	Quetiapine SR n=49 Participants Quetiapine SR (sustained release)	Divalproex Sodium ER n=49 Participants Divalproex Sodium ER (extended release)	Placebo n=51 Participants Placebo control	Total n=149 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=49 Participants	0 Participants n=49 Participants	0 Participants n=51 Participants	0 Participants n=149 Participants
Age, Categorical Between 18 and 65 years	49 Participants n=49 Participants	49 Participants n=49 Participants	51 Participants n=51 Participants	149 Participants n=149 Participants
Age, Categorical >=65 years	0 Participants n=49 Participants	0 Participants n=49 Participants	0 Participants n=51 Participants	0 Participants n=149 Participants
Age, Continuous	41.4 years STANDARD_DEVIATION 12.1 • n=49 Participants	37.5 years STANDARD_DEVIATION 12.0 • n=49 Participants	37.6 years STANDARD_DEVIATION 11.6 • n=51 Participants	38.8 years STANDARD_DEVIATION 12.0 • n=149 Participants
Sex: Female, Male Female	28 Participants n=49 Participants	27 Participants n=49 Participants	33 Participants n=51 Participants	88 Participants n=149 Participants
Sex: Female, Male Male	21 Participants n=49 Participants	22 Participants n=49 Participants	18 Participants n=51 Participants	61 Participants n=149 Participants
Region of Enrollment United States	49 participants n=49 Participants	49 participants n=49 Participants	51 participants n=51 Participants	149 participants n=149 Participants
Clinical Global Impression - Severity scale (CGI-S)	5.4 units on a scale STANDARD_DEVIATION .5 • n=49 Participants	5.3 units on a scale STANDARD_DEVIATION .6 • n=49 Participants	5.4 units on a scale STANDARD_DEVIATION .6 • n=51 Participants	5.4 units on a scale STANDARD_DEVIATION .6 • n=149 Participants
Hamilton Anxiety Scale (HAM-A)	41.4 units on a scale STANDARD_DEVIATION 12.1 • n=49 Participants	37.5 units on a scale STANDARD_DEVIATION 12.0 • n=49 Participants	37.6 units on a scale STANDARD_DEVIATION 11.6 • n=51 Participants	38.8 units on a scale STANDARD_DEVIATION 12.0 • n=149 Participants
Sheehan Panic Disorder Scale (SPS)	47.5 units on a scale STANDARD_DEVIATION 17.8 • n=49 Participants	42.4 units on a scale STANDARD_DEVIATION 18.5 • n=49 Participants	41.8 units on a scale STANDARD_DEVIATION 19.5 • n=51 Participants	43.9 units on a scale STANDARD_DEVIATION 18.7 • n=149 Participants
Montgomery Asberg Depression Rating Scale (MADRS)	26.4 units on a scale STANDARD_DEVIATION 8.3 • n=49 Participants	24.5 units on a scale STANDARD_DEVIATION 7.3 • n=49 Participants	25.8 units on a scale STANDARD_DEVIATION 7.9 • n=51 Participants	25.6 units on a scale STANDARD_DEVIATION 7.8 • n=149 Participants
Young Mania Rating Scale (YMRS)	11.2 units on a scale STANDARD_DEVIATION 6.1 • n=49 Participants	12.3 units on a scale STANDARD_DEVIATION 7.9 • n=49 Participants	11.2 units on a scale STANDARD_DEVIATION 5.7 • n=51 Participants	11.6 units on a scale STANDARD_DEVIATION 6.6 • n=149 Participants
Sheehan Disability Scale (SDS)	15.1 units on a scale STANDARD_DEVIATION 6.8 • n=49 Participants	12.9 units on a scale STANDARD_DEVIATION 7.9 • n=49 Participants	14.8 units on a scale STANDARD_DEVIATION 7.4 • n=51 Participants	14.3 units on a scale STANDARD_DEVIATION 7.4 • n=149 Participants
Rapid Ideas Scale	54.0 units on a scale STANDARD_DEVIATION 17.3 • n=49 Participants	52.1 units on a scale STANDARD_DEVIATION 20.9 • n=49 Participants	51.7 units on a scale STANDARD_DEVIATION 19.1 • n=51 Participants	52.6 units on a scale STANDARD_DEVIATION 19.1 • n=149 Participants
Sheehan Irritability Scale (SIS)	48.9 units on a scale STANDARD_DEVIATION 11.5 • n=49 Participants	43.2 units on a scale STANDARD_DEVIATION 16.4 • n=49 Participants	43.5 units on a scale STANDARD_DEVIATION 13.9 • n=51 Participants	45.2 units on a scale STANDARD_DEVIATION 14.2 • n=149 Participants
Suicidality Tracking Scale	1.9 units on a scale STANDARD_DEVIATION 2.6 • n=19 Participants • This scale was only administered to the last 74 patients in the trial	1.8 units on a scale STANDARD_DEVIATION 2.8 • n=28 Participants • This scale was only administered to the last 74 patients in the trial	1.0 units on a scale STANDARD_DEVIATION 1.5 • n=27 Participants • This scale was only administered to the last 74 patients in the trial	1.5 units on a scale STANDARD_DEVIATION 2.3 • n=74 Participants • This scale was only administered to the last 74 patients in the trial

PRIMARY outcome

Timeframe: 8 weeks (using LOCF Repeated Measures ANOVA)

The CGI-21 Anxiety is a 21-point clinician-rated global improvement for anxiety symptoms. Response range: -10 to +10. The higher the score the more improvement. At Baseline all patients have a score of "0" (zero), against which any subsequent improvements or deterioration is assessed. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA). The focus was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANOVA. Outcomes showing scores above zero indicate that patients did better, i.e. showed improvement on this scale.

Outcome measures

Measure	Quetiapine SR n=47 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=46 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=51 Participants placebo placebo: placebo
Change From Baseline in the CGI-21 Anxiety	4.9 score on a scale Standard Error 0.62	2.9 score on a scale Standard Error 0.63	3.4 score on a scale Standard Error 0.60

SECONDARY outcome

Timeframe: 8 weeks

The PGI-21 Anxiety is a 21-point patient-rated global improvement for anxiety symptoms. Response range: -10 to +10. The higher the score the more improvement. At Baseline all patients have a score of "0" (zero), against which any subsequent improvements or deterioration is assessed. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA). The focus was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANOVA. Outcomes showing scores above zero indicate that patients did better, i.e. showed improvement on this scale.

Outcome measures

Measure	Quetiapine SR n=47 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=46 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=51 Participants placebo placebo: placebo
Change From Baseline on Patient Global Improvement Scale (PGI-21) for Anxiety Symptoms	3.9 score on a scale Standard Error 0.68	1.9 score on a scale Standard Error 0.69	2.3 score on a scale Standard Error 0.65

SECONDARY outcome

Timeframe: 8 weeks

Hamilton Anxiety Scale (HAM-A) measures severity of anxiety symptoms - range of scores is 0-56. A higher score means worse anxiety. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA) in which baseline and each of the 8 weekly assessments were the within subject factors (labeled "time") and treatment group (labeled "treatment") was the between-subjects factor with 3 levels. The focus was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANCOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANCOVA. Outcome results with a "minus" score indicate that patients did better, i.e. had a reduction in symptoms on this scale.

Outcome measures

Measure	Quetiapine SR n=47 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=46 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=51 Participants placebo placebo: placebo
Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores	-11.7 score on a scale Standard Error 1.32	-6.4 score on a scale Standard Error 1.30	-8.4 score on a scale Standard Error 1.4

SECONDARY outcome

Timeframe: 8 weeks

Sheehan Panic Disorder Scale (SPS). Range of scores: 0-140. Higher scores indicate greater severity of symptoms. The relative efficacy of quetiapine SR vs. divalproex ER and placebo was tested using a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA) in which baseline and each of the 8 weekly assessments for the efficacy variables were the within subject factors ("time") and treatment group ("treatment") was the between-subjects factor with 3 levels. The focus in this analysis was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in efficacy measures were tested using LOCF ANCOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the baseline-to-endpoint LOCF ANCOVA. Outcome results with a "minus" indicate that patients did better, i.e. had a reduction in symptoms on this scale.

Outcome measures

Measure	Quetiapine SR n=47 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=46 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=51 Participants placebo placebo: placebo
Change From Baseline in Sheehan Panic Disorder Scale (SPS)	-24.4 score on a scale Standard Error 2.9	-14.8 score on a scale Standard Error 2.9	-18.3 score on a scale Standard Error 2.8

SECONDARY outcome

Timeframe: 8 weeks

Montgomery Asberg Depression Rating Scale (MADRS) measures severity of depressive symptoms. Range of scores: 0-60. A higher score shows greater severity of depressive symptoms. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA) in which baseline and each of the 8 weekly assessments were the within subject factors ("time") and treatment group ("treatment") was the between-subjects factor with 3 levels. The central focus was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in efficacy were tested using LOCF ANCOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANCOVA. Outcome results with a "minus" score indicate that patients did better, i.e had a reduction in symptoms on this scale.

Outcome measures

Measure	Quetiapine SR n=47 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=46 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=51 Participants placebo placebo: placebo
Change From Baseline on Montgomery Asberg Depression Rating Scale (MADRS)	-11.5 score on a scale Standard Error 1.5	-5.5 score on a scale Standard Error 1.6	-7.3 score on a scale Standard Error 1.5

SECONDARY outcome

Timeframe: 8 weeks

Young Mania Rating Scale (YMRS) measures severity of mania / hypomania symptoms. Range of scores: 0-60. A higher score shows worse mania / hypomania. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA) in which baseline and each of the 8 weekly assessments were the within subject factors ("time") and treatment group ("treatment") was the between-subjects factor with 3 levels. The focus was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANCOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANCOVA. Outcome results with a "minus" score indicate that patients did better, i.e. had a reduction in symptoms on this scale.

Outcome measures

Measure	Quetiapine SR n=47 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=46 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=51 Participants placebo placebo: placebo
Change From Baseline in Young Mania Rating Scale (YMRS)	-5.4 score on a scale Standard Error 1.2	-4.4 score on a scale Standard Error 1.2	-4.3 score on a scale Standard Error 1.1

SECONDARY outcome

Timeframe: 8 weeks

Clinician Global Impression Scale for Bipolar Disorder (CGI-BP) measures the severity of bipolar disorder symptoms overall. Range of response: i1. normal, not ill to 7. very severely ill. A higher score represents greater severity. A last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA) in which baseline and each of the 8 weekly assessments were the within subject factors ("time") and treatment group ("treatment") was the between-subjects factor with 3 levels was used. The focus was on the "treatment-by-time" effect and whether the trajectory of response differed over time by treatment. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANCOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANCOVA. Outcome results with a "minus" score indicate that patients did better, i.e. had a reduction in symptoms on this scale.

Outcome measures

Measure	Quetiapine SR n=47 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=46 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=51 Participants placebo placebo: placebo
Change From Baseline on Clinician Global Impression Scale for Bipolar Disorder (CGI-BP) (Overall Severity)	-1.2 score on a scale Standard Error .16	-.5 score on a scale Standard Error .17	-1.0 score on a scale Standard Error .16

SECONDARY outcome

Timeframe: 8 weeks

Rapid ideas Scale (RISc) measures severity of rapid thoughts. Range of scores is 0-100. A higher score means more severe rapidity of thinking. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA) in which baseline and each of the 8 weekly assessments were the within subject factors ("time") and treatment group ("treatment") was the between-subjects factor with 3 levels. The focus was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANCOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANCOVA. Outcome results with a "minus" score indicate that patients did better, i.e. had a reduction in symptoms on this scale.

Outcome measures

Measure	Quetiapine SR n=47 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=46 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=51 Participants placebo placebo: placebo
Change From Baseline on Rapid Ideas Scale (RISc)	-28.9 score on a scale Standard Error 3.4	-19.7 score on a scale Standard Error 3.4	-23.1 score on a scale Standard Error 3.3

SECONDARY outcome

Timeframe: 8 weeks

Sheehan Irritability Scale (SIS) measures severity of anxiety symptoms. Range of scores: 0-70. A higher score shows worse irritability. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA) in which baseline and each of the 8 weekly assessments were the within subject factors ("time") and treatment group ("treatment") was the between-subjects factor with 3 levels. The focus was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANCOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANCOVA. Outcome results with a "minus" score indicate that patients did better, i.e. had a reduction in symptoms on this scale.

Outcome measures

Measure	Quetiapine SR n=47 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=46 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=51 Participants placebo placebo: placebo
Change From Baseline in Sheehan Irritability Scale (SIS)	-29.8 score on a scale Standard Error 3.4	-22.6 score on a scale Standard Error 3.4	-19.4 score on a scale Standard Error 3.3

SECONDARY outcome

Timeframe: 8 weeks

Sheehan Disability Scale (SDS) measures severity of functional impairment or disability. There are 4 scores: 1) Work Disability 2) Social Disability 3) Family Life Disability. Each of these domains is scored 0-10, with a higher score representing greater disability or functional impairment. These 3 domain scores are added to give a Total Disability scale score. Range of response for Total Disability: 0 to 30. A higher score shows greater disability/functional impairment. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA). Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANCOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANCOVA. Outcome results with a "minus" score indicate that patients did better, i.e. had a reduction in symptoms on this scale.

Outcome measures

Measure	Quetiapine SR n=47 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=46 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=51 Participants placebo placebo: placebo
Change From Baseline on Sheehan Disability Scale (SDS) - Total	-6.5 score on a scale Standard Error 1.8	-3 score on a scale Standard Error 1.2	-5.3 score on a scale Standard Error 1.1

SECONDARY outcome

Timeframe: 8 weeks

Population: Only administered to the last 74 patients enrolled after November 2008

Sheehan - Suicidality Tracking Scale S-STS (2008 version with 8 items) measures severity of a range of suicidality symptoms. Range of scores: 0-32. A higher score represents more severe suicidality. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA) in which baseline and each of the 8 weekly assessments were the within subject factors ("time") and treatment group ("treatment") was the between-subjects factor with 3 levels. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANCOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANCOVA. Outcome results with a "minus" score indicate that patients did better, i.e. had a reduction in symptoms on this scale..

Outcome measures

Measure	Quetiapine SR n=19 Participants Quetiapine SR quetiapine SR: flexible dosing, 50 mg up to a maximum of 300 mg per day for 8 weeks	Divalproex Sodium ER n=28 Participants Divalproex Sodium ER divalproex sodium ER: Flexible dosing, 500 mg up to a maximum of 3000 mg per day for 8 weeks	Placebo n=27 Participants placebo placebo: placebo
Change From Baseline on Sheehan- Suicidality Tracking Scale S-STS (2008 Version With 8 Items)	-.95 score on a scale Standard Error .44	-.07 score on a scale Standard Error .36	-.3 score on a scale Standard Error .38

Adverse Events

Quetiapine SR

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Divalproex Sodium ER

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Quetiapine SR n=49 participants at risk Quetiapine SR (sustained release)	Divalproex Sodium ER n=49 participants at risk Divalproex Sodium ER (extended release)	Placebo n=51 participants at risk Placebo control
Psychiatric disorders worsening depression	2.0% 1/49 • Number of events 1	2.0% 1/49 • Number of events 1	2.0% 1/51 • Number of events 1
Cardiac disorders fainted	0.00% 0/49	2.0% 1/49 • Number of events 1	0.00% 0/51
Skin and subcutaneous tissue disorders spider bite	0.00% 0/49	2.0% 1/49 • Number of events 1	0.00% 0/51
Musculoskeletal and connective tissue disorders back pain	0.00% 0/49	0.00% 0/49	2.0% 1/51 • Number of events 1

Other adverse events

Measure	Quetiapine SR n=49 participants at risk Quetiapine SR (sustained release)	Divalproex Sodium ER n=49 participants at risk Divalproex Sodium ER (extended release)	Placebo n=51 participants at risk Placebo control
Nervous system disorders Drowsiness/Sleepiness	49.0% 24/49	36.7% 18/49	33.3% 17/51
Gastrointestinal disorders Dry Mouth	30.6% 15/49	6.1% 3/49	13.7% 7/51
Gastrointestinal disorders Nausea or Nausea/Vomiting	18.4% 9/49	24.5% 12/49	27.5% 14/51
Skin and subcutaneous tissue disorders Tingling	16.3% 8/49	2.0% 1/49	2.0% 1/51
Gastrointestinal disorders Increased appetite	14.3% 7/49	12.2% 6/49	13.7% 7/51
Nervous system disorders Sedation	12.2% 6/49	6.1% 3/49	5.9% 3/51
Nervous system disorders Headache	8.2% 4/49	24.5% 12/49	23.5% 12/51
Nervous system disorders Lightheadednessa	8.2% 4/49	4.1% 2/49	2.0% 1/51
Nervous system disorders Tiredness	6.1% 3/49	2.0% 1/49	5.9% 3/51
Gastrointestinal disorders Diarrheaa	2.0% 1/49	4.1% 2/49	7.8% 4/51
Nervous system disorders Dizzinessa	2.0% 1/49	6.1% 3/49	2.0% 1/51

Additional Information

David V. Sheehan, MD, MBA

University of South Florida College of Medicine

Phone: 813-974-4544

Email: dsheehan@health.usf.edu

Results disclosure agreements

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