Trial Outcomes & Findings for Does Pharmacological Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Adults Enhance Parenting Performance? (NCT NCT01127607)

NCT ID: NCT01127607

Last Updated: 2014-06-13

Results Overview

Observations of parents and children as they interact with each other during a five minute homework task and during a 10 minute non-academic task. Interactions were recorded and later coded by trained observers. Observers counted number of parent and child behaviors. Average number of behaviors per group were computed. Three subjects dropped prior to completing this assessment and one participant completed the other endpoint measures but not the DPICS, which is why the total N for this outcome is 23 at study endpoint. At end of period II (study endpoint), the medication group (n=10) was compared to the placebo group (N=13).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 38 participants
• Primary outcome timeframe: study endpoint- end of period II (between subjects trial)
• Results posted on: 2014-06-13

Participant Flow

Participants were recruited by direct advertisement as well as from referrals from mental health and medical providers.

Participants first stabilized on LDX in 3 week open label trial starting at 30mg + increasing by 20mg/week until optimal dose was found. Those unable to tolerate LDX or not responsive to it were discontinued. 38 enrolled; 8 dropped out due to adverse events + 3 were lost to follow up in med phase, leaving 27.

Participant milestones

Measure	Placebo Arm All 27 Participants were first optimized on lisdexamfetamine (LDX) (30mg, 50mg or 70mg) over 3 weeks then underwent within-subjects comparison with each subject completed one parent child interaction task (DPICS) once on optimal LDX dose and one parent child interaction task once on placebo (Period 1). The 14 subjects assigned to this arm were then switched to blinded placebo for the parallel group, between subjects trial (period II) which lasted until the final endpoint assessment. These subjects received only placebo during period II.	Treatment Arm All 27 Participants were first optimized on lisdexamfetamine (LDX) (30mg, 50mg or 70mg) over 3 weeks then underwent within-subjects comparison with each subject completed one parent child interaction task (DPICS) once on optimal LDX dose and one parent child interaction task once on placebo (Period I). The 13 subjects assigned to this arm were then switched to blinded optimal dose of LDX for the parallel group, between subjects trial (period II) which lasted until the final endpoint assessment. These subjects received only their optimal dose of LDX during period II.
Phase I (Within Subjects) STARTED	14	13
Phase I (Within Subjects) COMPLETED	14	13
Phase I (Within Subjects) NOT COMPLETED	0	0
Phase II (Between Subjects) STARTED	14	13
Phase II (Between Subjects) COMPLETED	13	11
Phase II (Between Subjects) NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Placebo Arm All 27 Participants were first optimized on lisdexamfetamine (LDX) (30mg, 50mg or 70mg) over 3 weeks then underwent within-subjects comparison with each subject completed one parent child interaction task (DPICS) once on optimal LDX dose and one parent child interaction task once on placebo (Period 1). The 14 subjects assigned to this arm were then switched to blinded placebo for the parallel group, between subjects trial (period II) which lasted until the final endpoint assessment. These subjects received only placebo during period II.	Treatment Arm All 27 Participants were first optimized on lisdexamfetamine (LDX) (30mg, 50mg or 70mg) over 3 weeks then underwent within-subjects comparison with each subject completed one parent child interaction task (DPICS) once on optimal LDX dose and one parent child interaction task once on placebo (Period I). The 13 subjects assigned to this arm were then switched to blinded optimal dose of LDX for the parallel group, between subjects trial (period II) which lasted until the final endpoint assessment. These subjects received only their optimal dose of LDX during period II.
Phase II (Between Subjects) Lost to Follow-up	0	2
Phase II (Between Subjects) Withdrawal by Subject	1	0

Baseline Characteristics

Does Pharmacological Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Adults Enhance Parenting Performance?

Baseline characteristics by cohort

Measure	Placebo Arm n=14 Participants Participants in this arm were first optimized on lisdexamfetamine (30mg, 50mg or 70mg) over 3 weeks then switched to blinded placebo for the 4 weeks of the parallel group trial	Treatment Arm n=13 Participants Participants in this arm were first optimized on lisdexamfetamine (30mg, 50mg or 70mg) over 3 weeks then switched to blinded matching doses of lisdexamfetamine for 4 weeks of the parallel group trial.	Total n=27 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants	13 Participants n=7 Participants	27 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	41.38 years STANDARD_DEVIATION 4.41 • n=5 Participants	40.69 years STANDARD_DEVIATION 6.06 • n=7 Participants	41.04 years STANDARD_DEVIATION 5.20 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	13 participants n=7 Participants	27 participants n=5 Participants

PRIMARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

Population: Task situation (homework vs. non-academic) was within-subjects; all participants completed both types of interactions. Medication was between subjects.

Observations of parents and children as they interact with each other during a five minute homework task and during a 10 minute non-academic task. Interactions were recorded and later coded by trained observers. Observers counted number of parent and child behaviors. Average number of behaviors per group were computed. Three subjects dropped prior to completing this assessment and one participant completed the other endpoint measures but not the DPICS, which is why the total N for this outcome is 23 at study endpoint. At end of period II (study endpoint), the medication group (n=10) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=13 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task n=10 Participants Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task n=10 Participants Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Counts inappropriate child behavior	6.8 behaviors Standard Deviation 6.2	1.4 behaviors Standard Deviation 2.5	3.8 behaviors Standard Deviation 4.7	1.5 behaviors Standard Deviation 1.9
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Counts Verbalizations	67.2 behaviors Standard Deviation 35.4	42.1 behaviors Standard Deviation 16.2	53.8 behaviors Standard Deviation 31.6	40.1 behaviors Standard Deviation 24.0
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Counts Commands	14.5 behaviors Standard Deviation 8.8	9.0 behaviors Standard Deviation 4.2	11.0 behaviors Standard Deviation 6.6	4.9 behaviors Standard Deviation 3.3

PRIMARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

Population: Task situation (homework vs. non-academic) was within-subjects; all participants completed both types of interactions. Medication was between subjects.

Observations of parents and children as they interact with each other during a five minute homework task and during a 10 minute non-academic task. Interactions were recorded and later coded by trained observers. Observers counted number of parent and child behaviors. Percentages of behaviors as a function of total verbalizations (for praise, negative talk, demanding) or as a function of commands and questions (for impatient and responsive) were computed.Three subjects dropped prior to completing this assessment and one participant completed the other endpoint measures but not the DPICS, which is why the total N for this outcome is 23 at study endpoint. At end of period II (study endpoint), the medication group (n=10) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=13 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task n=10 Participants Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task n=10 Participants Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Percentages Parent responsive	69.8 Percentage of behaviors Standard Deviation 33.3	89.7 Percentage of behaviors Standard Deviation 18.1	63.8 Percentage of behaviors Standard Deviation 35.8	77.3 Percentage of behaviors Standard Deviation 18.8
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Percentages Parent praise	1.2 Percentage of behaviors Standard Deviation 2.2	6.0 Percentage of behaviors Standard Deviation 6.0	2.8 Percentage of behaviors Standard Deviation 2.5	5.7 Percentage of behaviors Standard Deviation 6.2
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Percentages Parent negative talk	5.3 Percentage of behaviors Standard Deviation 4.3	5.9 Percentage of behaviors Standard Deviation 8.6	21.1 Percentage of behaviors Standard Deviation 21.0	12.6 Percentage of behaviors Standard Deviation 10.2
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Percentages Parent demandingness	21.8 Percentage of behaviors Standard Deviation 8.9	23.5 Percentage of behaviors Standard Deviation 10.9	21.7 Percentage of behaviors Standard Deviation 10.1	12.7 Percentage of behaviors Standard Deviation 6.5
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Percentages Parent impatient	42.4 Percentage of behaviors Standard Deviation 11.3	38.7 Percentage of behaviors Standard Deviation 20.7	34.1 Percentage of behaviors Standard Deviation 12.9	26.3 Percentage of behaviors Standard Deviation 11.0

SECONDARY outcome

Timeframe: baseline and week 4

Population: Used a within-subjects evaluation; the same 24 participants evaluated in both arms.

measures change in parenting practices.The APQ is a 42-item measure (each item ranges from 1/always to 5/never) on which parents are asked to indicate the frequency with which they implement the following parenting practices: involvement (10 items range 10-50- higher scores mean more parental involvement), positive parenting (6 items with range of 6 to 30 and higher scores indicate greater use of praise), poor monitoring/supervision (10 items with range of 10 to 50 and higher scores indicate less supervision/monitoring), inconsistent discipline(6 items with range of 6 to 30 and higher scores indicate greater problems with inconsistent discipline), and corporal punishment (3 items with range of 3-15 and greater scores indicate more use of corporal punishment). Items are rated on a 5-point scale, ranging from 1 ("never") to 5 ("always"). Items summed into composite scales.

Within subject comparison of no medication baseline vs. optimal dose medication.

Outcome measures

Measure	Unmedicated n=24 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=24 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Alabama Parenting Questionnaire (APQ) Parent Involvement	37.83 units on a scale Standard Deviation 5.64	38.82 units on a scale Standard Deviation 5.30	—	—
Alabama Parenting Questionnaire (APQ) Positive parenting	25.42 units on a scale Standard Deviation 3.60	25.58 units on a scale Standard Deviation 2.86	—	—
Alabama Parenting Questionnaire (APQ) Poor monitoring and poor supervision	14.25 units on a scale Standard Deviation 3.84	13.58 units on a scale Standard Deviation 3.20	—	—
Alabama Parenting Questionnaire (APQ) Inconsistent discipline	15.79 units on a scale Standard Deviation 3.51	14.62 units on a scale Standard Deviation 3.87	—	—
Alabama Parenting Questionnaire (APQ) Corporal punishment	4.79 units on a scale Standard Deviation 2.04	4.42 units on a scale Standard Deviation 1.72	—	—

SECONDARY outcome

Timeframe: baseline and week 4

Population: Used a within-subjects design; the same 24 participants measured in both arms.

Parent ratings of their child's symptoms of attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). Measure consists of 45 items each rated on a Likert scale that ranges from 0 (not at all) to 3 (very much). Items are averaged to form adhd-inattention, adhd-hyperactive/impulsive, ODD, and CD scores.Within subject comparison of no medication baseline vs. optimal dose medication. ADHD subscale consists of 20 items with range of 0 to 60. ODD subscale consists of 9 items with range of 0 to 27. CD subscale consists of 15 items with range of 0 to 45. For all subscales, higher scores indicate more severe symptoms.

Outcome measures

Measure	Unmedicated n=24 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=24 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Disruptive Behavior Disorders Rating Scale (DBD) ADHD-hyperactive/impulsive symptom score	1.55 units on a scale Standard Deviation 0.76	1.34 units on a scale Standard Deviation 0.61	—	—
Disruptive Behavior Disorders Rating Scale (DBD) ADHD-inattentive symptom score	2.11 units on a scale Standard Deviation 0.59	1.85 units on a scale Standard Deviation 0.74	—	—
Disruptive Behavior Disorders Rating Scale (DBD) ODD symptom score	1.17 units on a scale Standard Deviation 0.69	1.12 units on a scale Standard Deviation 0.69	—	—
Disruptive Behavior Disorders Rating Scale (DBD) CD symptom score	0.16 units on a scale Standard Deviation 0.14	0.18 units on a scale Standard Deviation 0.24	—	—

SECONDARY outcome

Timeframe: baseline and week 4

Population: Uses a within-subjects evaluation; the same 25 participants are in both arms.

Parent ratings of their child's functioning and need for treatment in developmentally important domains. Ratings are completed using visual-analogue scales that are anchored at the low end by "no problems / no need for treatment" and at the high end by "extreme problem / definitely needs treatment." Visual analogue ratings for each subscale were converted to 0 to 6 scales with higher values indicating greater impairment and lower values indicating less impairment for each subscale.Within subject comparison of no medication baseline vs. optimal dose medication.

Outcome measures

Measure	Unmedicated n=24 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=24 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Impairment Rating Scale (IRS) Child's peer relationship impairment	2.75 units on a 0 to 6 scale Standard Deviation 2.15	2.21 units on a 0 to 6 scale Standard Deviation 1.69	—	—
Impairment Rating Scale (IRS) Child's sibling relationship impairment	2.82 units on a 0 to 6 scale Standard Deviation 2.34	2.68 units on a 0 to 6 scale Standard Deviation 1.99	—	—
Impairment Rating Scale (IRS) Child's parent relationship impairment	3.67 units on a 0 to 6 scale Standard Deviation 1.88	3.79 units on a 0 to 6 scale Standard Deviation 1.56	—	—
Impairment Rating Scale (IRS) Child's academic impairment	3.75 units on a 0 to 6 scale Standard Deviation 2.13	3.29 units on a 0 to 6 scale Standard Deviation 2.03	—	—
Impairment Rating Scale (IRS) Child's self-esteem impairment	3.92 units on a 0 to 6 scale Standard Deviation 1.95	3.54 units on a 0 to 6 scale Standard Deviation 1.72	—	—
Impairment Rating Scale (IRS) Child's family impairment	4.00 units on a 0 to 6 scale Standard Deviation 1.83	3.87 units on a 0 to 6 scale Standard Deviation 1.49	—	—
Impairment Rating Scale (IRS) Child's overall impairment	3.63 units on a 0 to 6 scale Standard Deviation 1.86	3.42 units on a 0 to 6 scale Standard Deviation 1.59	—	—

SECONDARY outcome

Timeframe: baseline and week 4

Population: Uses a within-subjects design; the same 25 participants are in both arms.

The SDS consists of 3 self rated items assessing the degree to which symptoms affect work/school, social life, and family/home responsibilities. Items are rated on a 0 (not at all) to 10 (extremely) scale. Items were averaged into an overall disability score with range of 0 to 10 with higher scores indicating more severe disability.Within subject comparison of no medication baseline vs. optimal dose medication.

Outcome measures

Measure	Unmedicated n=25 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=25 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Sheehan Disability Scale (SDS)	6.26 units on a 0 to 10 scale Standard Deviation 2.11	3.17 units on a 0 to 10 scale Standard Deviation 2.65	—	—

SECONDARY outcome

Timeframe: weeks 4 and weeks 5 (period I within subjects trial)

Population: Used a within-subjects design for this phase; the same 26 participants completed all four arms.

Observations of parents and children as they interact with each other during a five minute homework task and during a 10 minute non-academic task. Interactions were recorded and later coded by trained observers. Observers counted number of parent and child behaviors with each parent-child dyad counted as one participant. Average number of behaviors per group were computed.This outcome was part of period I- the within subject comparison of all participating subjects once on placebo (n=26) and once with all subjects on active medication (N=26). (the 27th participant completed this phase but partial data was lost due to mechanical failure with video equipment so their data was not included). All adult participants received both placebo and active medication in this phase that comprised all of period 1.

Outcome measures

Measure	Unmedicated n=26 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=26 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task n=26 Participants Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task n=26 Participants Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Dyadic Parent-Child Interaction Coding System (DPICS) Verbalizations	61.7 behaviors Standard Deviation 30.9	58.2 behaviors Standard Deviation 31.1	45.2 behaviors Standard Deviation 21.1	48.6 behaviors Standard Deviation 26.5
Dyadic Parent-Child Interaction Coding System (DPICS) Commands	15.4 behaviors Standard Deviation 11.5	14.8 behaviors Standard Deviation 10.3	8.7 behaviors Standard Deviation 5.2	8.3 behaviors Standard Deviation 4.1
Dyadic Parent-Child Interaction Coding System (DPICS) inappropriate child behavior	6.1 behaviors Standard Deviation 10.0	3.3 behaviors Standard Deviation 4.9	2.5 behaviors Standard Deviation 2.1	3.8 behaviors Standard Deviation 5.4

SECONDARY outcome

Timeframe: weeks 4 and weeks 5 (period I within subjects trial)

Population: Used a within-subjects design; the same 26 participants completed all arms.

Observations of parents and children as they interact with each other during a five minute homework task and during a 10 minute non-academic task. Interactions were recorded and later coded by trained observers. Observers counted number of parent and child behaviors with each parent-child dyad counted as one participant. Percentages of behaviors as a function of total verbalizations (for praise, negative talk, demanding) or as a function of commands and questions (for impatient and responsive) were computed. This outcome was part of period I- the within subject comparison of all participating subjects once on placebo (n=26) and once with all subjects on active medication (N=26). (the 27th participant completed this phase but partial data was lost due to mechanical failure with video equipment so their data was not included). All adult participants received both placebo and active medication in this phase that comprised all of period 1.

Outcome measures

Measure	Unmedicated n=26 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=26 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task n=26 Participants Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task n=26 Participants Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Percentages Parent praise	2.6 Percentage of behaviors Standard Deviation 3.7	3.0 Percentage of behaviors Standard Deviation 4.5	3.6 Percentage of behaviors Standard Deviation 5.8	2.2 Percentage of behaviors Standard Deviation 2.5
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Percentages Parent negative talk	4.7 Percentage of behaviors Standard Deviation 5.7	4.0 Percentage of behaviors Standard Deviation 3.6	14.4 Percentage of behaviors Standard Deviation 11.7	9.1 Percentage of behaviors Standard Deviation 8.7
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Percentages Parent demandingness	24.1 Percentage of behaviors Standard Deviation 10.7	25.7 Percentage of behaviors Standard Deviation 11.3	19.3 Percentage of behaviors Standard Deviation 6.4	19.2 Percentage of behaviors Standard Deviation 10.5
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Percentages Parent impatient	39.2 Percentage of behaviors Standard Deviation 12.8	42.5 Percentage of behaviors Standard Deviation 18.7	31.2 Percentage of behaviors Standard Deviation 15.7	32.6 Percentage of behaviors Standard Deviation 10.4
Dyadic Parent-Child Interaction Coding System (DPICS) - Behavior Percentages Parent responsive	83.2 Percentage of behaviors Standard Deviation 25.9	74.8 Percentage of behaviors Standard Deviation 30.4	75.9 Percentage of behaviors Standard Deviation 15.3	79.8 Percentage of behaviors Standard Deviation 12.8

SECONDARY outcome

Timeframe: baseline and end of dose optimization phase/week 4

Population: Within-subjects analysis; same 26 participants are in the unmedicated and optimal dose of medication arms.

rates 13 potential adverse events of central nervous system stimulant medications on a 0-3 likert scale with 0=none 1=mild severity, 2=moderate severity, 3=severe severity. Form completed by participants at end of med optimization phase. Mean severity rating then averaged across 13 categories. This compares mean side effect severity at unmedicated baseline state vs. on optimal dose at week 3. Analysis includes all participants completing medication optimization.

Outcome measures

Measure	Unmedicated n=26 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=26 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Pittsburgh Side Effect Rating Scale	0.04 units on a scale Standard Deviation 0.12	0.26 units on a scale Standard Deviation 0.21	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

measures change in all DSM (Diagnostic and Statistics Manual) IV ADHD symptoms on a 0 (least severe) to 3 (most severe) scale. Inattention and hyperactive/impulsive subscales each consist of 9 items with range of 0 to 27. Total Score consists of all 18 items rated 0 to 3 with range of 0 to 54. For all, higher scores indicate more symptoms. All information obtained during clinician interview of patient. At endpoint, the medication group (N=11) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=11 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Adult ADHD Rating Scale (ADHD RS) Inattention	17.85 units on a scale Standard Deviation 8.21	8.82 units on a scale Standard Deviation 6.54	—	—
Adult ADHD Rating Scale (ADHD RS) Hyperactive/Impulsive	14.77 units on a scale Standard Deviation 8.23	5.64 units on a scale Standard Deviation 5.07	—	—
Adult ADHD Rating Scale (ADHD RS) Total Score	32.62 units on a scale Standard Deviation 15.61	14.46 units on a scale Standard Deviation 10.91	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

measures change in stress of parent child interactions and completed by the participant. The PSI is a measure of the source and degree of parenting stress (Abidin, 1995), which contains 120 items which are rated on a 1 (strongly disagree) to 5 (strongly agree) scale. 101 of these items are used to compute a total stress score (reported below) as the other 19 report on specific life stressors. Range is 101 to 505, for which higher scores indicate higher levels of stress. At endpoint, the medication group (N=9) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=9 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Parenting Stress Index (PSI)--Total Stress	241.54 units on a scale Standard Deviation 47.33	262.67 units on a scale Standard Deviation 38.84	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

self completed parenting measure of the degree to which parents feel they can influence their child's behavior. Measure consists of 25 items each rated using a Likert scales that ranges from 1 ("strongly disagree") to 5 ("strongly agree"). Range is 25 to 125 with higher scores indicating greater parental control over their child's behavior (desired outcome). At endpoint, the medication group (N=9) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=9 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Parenting Locus of Control (PLC)	79.00 units on a scale Standard Deviation 4.22	80.00 units on a scale Standard Deviation 5.57	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

Measures executive functioning using 40 items each rated using a Likert Scale that ranges from 0 ("never") to 3 ("almost daily"). Activation, Attention and effort subscales are 9 items each with range of 0-27. Affect scale is 7 items (range 0-21), memory is 6 items (range 0-18) and total score is 40 items (range 0-120). All raw scores are then reported as T scores based on normative data with higher T scores indicating worse executive functioning. At endpoint, the medication group (N=10) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=10 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Brown Attention Deficit Scale (BAADS) Total scale t-score	76.08 t score Standard Deviation 14.79	63.30 t score Standard Deviation 70.52	—	—
Brown Attention Deficit Scale (BAADS) Activation Scale t-score	73.38 t score Standard Deviation 11.52	66.4 t score Standard Deviation 13.5	—	—
Brown Attention Deficit Scale (BAADS) Attention Scale t-score	75.54 t score Standard Deviation 11.90	65.10 t score Standard Deviation 11.19	—	—
Brown Attention Deficit Scale (BAADS) Effort scale t-score	72.46 t score Standard Deviation 15.56	61.20 t score Standard Deviation 10.98	—	—
Brown Attention Deficit Scale (BAADS) Affect scale t-score	63.46 t score Standard Deviation 15.37	53.20 t score Standard Deviation 5.57	—	—
Brown Attention Deficit Scale (BAADS) Memory scale t-score	74.38 t score Standard Deviation 63.90	13.79 t score Standard Deviation 13.58	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

Measures child's interactions with peers and adults. Items rated using Likert scales that range from 0 ("never") to 2 ("often").At week 8, the medication group (N=10) was compared to the placebo group (N=11). There are two subscales: Problem Behaviors (18 items rated between 0-2 for total score range of 0 to 36) and Social Skills (40 items rated 0-2 with range for total score of 0-80). The total scores for these scales are reported as standard scores, with a population mean of 100 and standard deviation of 15. For problem behavior higher scores indicate worse behavior whereas for social skills, higher scores indicate more social (or better behavior).

Outcome measures

Measure	Unmedicated n=11 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=10 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Social Skills Rating System (SSRS) Social Skills Total Standard Score	86.64 standard scores Standard Deviation 17.72	89.90 standard scores Standard Deviation 13.68	—	—
Social Skills Rating System (SSRS) Problem Behavior Total Standard Score	113.81 standard scores Standard Deviation 12.54	111.80 standard scores Standard Deviation 16.55	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

measures externalizing symptoms in children.measures externalizing symptoms in children completed by their primary caretaker who was a participant in the study. The DBD (Pelham et al., 1992) assessed DSM symptoms of ADHD, ODD, and CD from 0 (not at all) to 3 (very much). The DBD includes symptoms of DSM-III and DSM-IV ADHD, Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD).At endpoint, the medication group (N=10) was compared to the placebo group (N=12).

Outcome measures

Measure	Unmedicated n=12 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=10 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Disruptive Behavior Disorder Rating Scale (DBD) Inattention	1.64 units on a scale Standard Deviation 0.76	1.60 units on a scale Standard Deviation 0.39	—	—
Disruptive Behavior Disorder Rating Scale (DBD) Hyperactive/Impulsive	1.25 units on a scale Standard Deviation 0.66	1.09 units on a scale Standard Deviation 0.62	—	—
Disruptive Behavior Disorder Rating Scale (DBD) Oppositional-defiant	1.04 units on a scale Standard Deviation 0.56	0.76 units on a scale Standard Deviation 0.54	—	—
Disruptive Behavior Disorder Rating Scale (DBD) Conduct disorder	0.17 units on a scale Standard Deviation 0.23	0.15 units on a scale Standard Deviation 0.16	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

measures global functioning of child rated by the parent who was the participant in the study. The IRS is a 7 item measure that uses visual-analogue scales to evaluate the child's problem level and need for treatment in developmentally important areas, such as peer relationships, adult-child relationships, academic performance. Each subscale including overall severity is scored from 0 (no problem) to 6 (extreme problem) with higher scores indicating more impairment. At endpoint, the medication group (N=10) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=10 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Impairment Rating Scale (IRS) Impairment with peers	2.62 units on a scale Standard Deviation 2.02	2.20 units on a scale Standard Deviation 2.04	—	—
Impairment Rating Scale (IRS) Impairment with siblings	2.17 units on a scale Standard Deviation 2.21	2.30 units on a scale Standard Deviation 1.89	—	—
Impairment Rating Scale (IRS) Impairment interferes with parents' relationship	3.15 units on a scale Standard Deviation 1.57	3.10 units on a scale Standard Deviation 1.85	—	—
Impairment Rating Scale (IRS) Academic impairment	3.15 units on a scale Standard Deviation 2.23	2.60 units on a scale Standard Deviation 2.07	—	—
Impairment Rating Scale (IRS) Self-esteem impairment	3.00 units on a scale Standard Deviation 2.04	3.40 units on a scale Standard Deviation 1.96	—	—
Impairment Rating Scale (IRS) General family impairment	3.08 units on a scale Standard Deviation 1.85	2.90 units on a scale Standard Deviation 1.85	—	—
Impairment Rating Scale (IRS) Overall severity	2.62 units on a scale Standard Deviation 1.66	2.70 units on a scale Standard Deviation 1.64	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

The SDS consists of 3 self rated items assessing the degree to which symptoms affect work/school, social life, and family/home responsibilities. Items are rated on a 0 (not at all) to 10 (extremely) scale. Items were averaged into an overall disability score with range of 0 to 10 with higher scores indicating more severe disability. At endpoint, the medication group (N=9) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=9 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Sheehan Disability Scale (SDS)	4.36 units on a scale Standard Deviation 2.60	2.26 units on a scale Standard Deviation 1.90	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

clinician rated measure of ADHD symptom severity in adult participants. The severity subscale is scored from 1 (normal) to 7 (extremely ill).At endpoint, the medication group (N=10) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=11 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
ADHD Severity Clinical Global Impressions Severity Subscale	3.78 units on a scale Standard Deviation 1.24	2.36 units on a scale Standard Deviation 0.81	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

Self completed by adult participants. Measures their child's functioning in the evening by asking them to report whether or not their child had problems in developmentally important areas. Number of problems per child are counted and counts are then averaged for each group with higher numbers representing more problems. At endpoint, the medication group (N=9) was compared to the placebo group (N=10).

Outcome measures

Measure	Unmedicated n=10 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=9 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Barkley Home Situations Questionnaire (HSQ)	9.30 number of child problems endorsed Standard Deviation 4.67	8.67 number of child problems endorsed Standard Deviation 5.22	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

rates 13 potential adverse events of Central Nervous System (CNS) stimulants on a 0-3 likert scale with 0=none 1=mild severity, 2=moderate severity, 3=severe severity. Form completed by participants. Mean severity rating then averaged across 13 categories.At endpoint, the medication group (N=10) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=10 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Pittsburgh Side Effect Rating Scale Mean Severity Rating.	0.28 units on a scale Standard Deviation 0.10	0.26 units on a scale Standard Deviation 0.12	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

Measured at rest at last assessment visit using an automated blood pressure machine; results reported in mmHG. At endpoint, the medication group (N=9) was compared to the placebo group (N=10).

Outcome measures

Measure	Unmedicated n=10 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=9 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Resting Blood Pressure systolic BP	123.40 mm Hg Standard Deviation 8.90	122.33 mm Hg Standard Deviation 11.45	—	—
Resting Blood Pressure diastolic BP	76.10 mm Hg Standard Deviation 8.74	75.11 mm Hg Standard Deviation 7.98	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

measures change in parenting practices.The APQ is a 42-item measure (each item ranges from 1/always to 5/never) on which parents are asked to indicate the frequency with which they implement the following parenting practices: involvement (10 items range 10-50- higher scores mean more parental involvement), positive parenting (6 items with range of 6 to 30 and higher scores indicate greater use of praise), poor monitoring/supervision (10 items with range of 10 to 50 and higher scores indicate less supervision/monitoring), inconsistent discipline(6 items with range of 6 to 30 and higher scores indicate greater problems with inconsistent discipline), and corporal punishment (3 items with range of 3-15 and greater scores indicate more use of corporal punishment). Items are rated on a 5-point scale, ranging from 1 ("never") to 5 ("always"). Items summed into composite scales.

At endpoint, the medication group (N=9) was compared to the placebo group (N=13).

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=9 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Alabama Parenting Questionnaire (APQ) Positive parenting	24.85 units on a scale Standard Deviation 3.46	24.33 units on a scale Standard Deviation 3.77	—	—
Alabama Parenting Questionnaire (APQ) Parental involvement	39.38 units on a scale Standard Deviation 5.38	37.78 units on a scale Standard Deviation 4.55	—	—
Alabama Parenting Questionnaire (APQ) Poor monitoring/supervision	12.23 units on a scale Standard Deviation 3.14	12.33 units on a scale Standard Deviation 2.40	—	—
Alabama Parenting Questionnaire (APQ) Inconsistent discipline	12.46 units on a scale Standard Deviation 3.84	14.22 units on a scale Standard Deviation 2.86	—	—
Alabama Parenting Questionnaire (APQ) Corporal punishment use	4.69 units on a scale Standard Deviation 1.80	3.89 units on a scale Standard Deviation 1.17	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

self rated measure of global impairment of adult participants derived from the child IRS. The IRS-A assesses impairment overall and in specific domains, including interpersonal relationships, academic performance, and self-esteem, and includes adult-specific domains of functioning, such as employment and romantic relationships. The IRS-A assesses current problems and need for treatment. Each subscale is rated from 0 (no problem) to 6 (extreme problem).At endpoint, the medication group (N=11) was compared to the placebo group (N=13). Overall Impairment is its own subscale and not a composite score of the others.

Outcome measures

Measure	Unmedicated n=13 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=11 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Impairment Rating Scale (IRS) Impairment with peers	2.38 units on a scale Standard Deviation 1.50	1.91 units on a scale Standard Deviation 1.70	—	—
Impairment Rating Scale (IRS) Impairment with parents	2.46 units on a scale Standard Deviation 2.03	1.30 units on a scale Standard Deviation 1.64	—	—
Impairment Rating Scale (IRS) General family impairment	2.77 units on a scale Standard Deviation 1.88	2.27 units on a scale Standard Deviation 1.79	—	—
Impairment Rating Scale (IRS) Academic impairment	3.60 units on a scale Standard Deviation 2.88	1.83 units on a scale Standard Deviation 2.04	—	—
Impairment Rating Scale (IRS) Self-esteem impairment	2.77 units on a scale Standard Deviation 2.09	2.00 units on a scale Standard Deviation 1.84	—	—
Impairment Rating Scale (IRS) Overall impairment	3.00 units on a scale Standard Deviation 1.73	2.55 units on a scale Standard Deviation 1.75	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

Weight measured on calibrated scale; participant measured without shoes or heavy clothing (jackets, sweaters, etc...). reported in kilograms.At endpoint, the medication group (N=9) was compared to the placebo group (N=11).

Outcome measures

Measure	Unmedicated n=11 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=9 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Weight	76.0 kg Standard Deviation 24.78	69.62 kg Standard Deviation 17.71	—	—

SECONDARY outcome

Timeframe: study endpoint- end of period II (between subjects trial)

measured at last assessment visit when at rest using an automated blood pressure machine; results reported in beats per minute. At endpoint, the medication group (N=8) was compared to the placebo group (N=9).

Outcome measures

Measure	Unmedicated n=9 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=8 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Resting Pulse	74.44 bpm Standard Deviation 7.58	77.13 bpm Standard Deviation 4.19	—	—

SECONDARY outcome

Timeframe: end of medication optimization phase/week 4

Population: Within-subjects analysis; data entered per dose not per subject. For example, if subject 1 took 30mg, 50mg and 70mgdoses during titration, they are recorded as three separate entries. Sample size reduces as dose increases because participants stopped at lowest acceptable dose and only moved to higher dose if they did not meet optimization criteria.

Self report of side effects measured during dose titration using the Pittsburgh Side Effects Rating Scale. Consists of 13 items each rated using 0(none) to 3 (severe) scales. Items endorsed as 1 (mild) or above were counted as present. Information on additional adverse events not part of the PSERS was collected by direct interview of the participants. All side effects occurring at a frequency of 5% or more are reported. Initial side effect data is reported for all participants entering pre-randomization med optimization phase who took medication (n=36) vs those formally enrolled (N=27). Also, side effect data for the med titration phase is entered per dose rather than per participant. For example, a person trying the 30, 50 and 70mg dose is entered is entered 4 times (no med as well) vs. just once. This is why baseline N is higher than for other outcomes collected at weeks 4 and 8 where data was only available for those completing the pre-randomization med optimization phase (N=27).

Outcome measures

Measure	Unmedicated n=38 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=36 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task n=21 Participants Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task n=17 Participants Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More Motor tics	0 Percent of participants	0 Percent of participants	0 Percent of participants	11.8 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More headaches	5.3 Percent of participants	36.1 Percent of participants	28.6 Percent of participants	29.4 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More tearful, sad, depressed	7.9 Percent of participants	13.9 Percent of participants	19.0 Percent of participants	11.8 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More socially withdrawn	5.3 Percent of participants	8.3 Percent of participants	0.0 Percent of participants	0.0 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More loss of appetite	0.0 Percent of participants	52.8 Percent of participants	66.7 Percent of participants	70.6 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More Buccal-lingual movement	2.6 Percent of participants	19.4 Percent of participants	28.6 Percent of participants	23.5 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More picking at skin	13.2 Percent of participants	11.1 Percent of participants	14.3 Percent of participants	5.9 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More worried/anxious	13.2 Percent of participants	36.1 Percent of participants	14.3 Percent of participants	17.6 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More dull, tired, listless	10.5 Percent of participants	16.7 Percent of participants	9.5 Percent of participants	11.8 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More stomachaches	0.0 Percent of participants	16.7 Percent of participants	4.8 Percent of participants	29.4 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More crabby, irritiable	10.5 Percent of participants	27.8 Percent of participants	23.8 Percent of participants	23.5 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More trouble sleeping	10.5 Percent of participants	30.6 Percent of participants	33.3 Percent of participants	35.3 Percent of participants
Pittsburgh Side Effects Rating Scale - Percent Present for All Reported Adverse Events Occurring at a Rate of 5% or More dry mouth	0.0 Percent of participants	30.6 Percent of participants	38.1 Percent of participants	70.5 Percent of participants

SECONDARY outcome

Timeframe: baseline and end of med optimization phase/week 4

Population: Uses a within-subjects design; the same 27 participants are in both arms.

Measures change in all DSM IV ADHD symptoms on a 0 (least severe) to 3 (most severe) scale. All information obtained during clinician interview of patient. Inattention and hyperactive/impulsive subscales each consist of 9 items with range of 0 to 27. Total Score consists of all 18 items (sum of two subscales) rated 0 to 3 with range of 0 to 54. For all, higher scores indicate more symptoms.

Outcome measures

Measure	Unmedicated n=27 Participants Data collected at intake, when participants were not on medication	Optimal Dose of Medication n=27 Participants Data collected after participants received 1 to 3 weeks of their optimal dose of LDX (either 30mg, 50mg or 70mg)	Medication - Homework Task Parent-child interaction during a homework task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)	Medication Non-academic Task Parent-child interaction during a non-academic task. Parents were on their optimal dose of lisdexamfetamine (30, 50, or 70 mg) and children were unmedicated. Parents and children did not have knowledge of parent treatment condition (medication versus placebo)
Adult ADHD Rating Scale Completed at the End of the Med Optimization Phase Total symptoms	40.85 scores on a scale Standard Deviation 7.55	17.77 scores on a scale Standard Deviation 8.51	—	—
Adult ADHD Rating Scale Completed at the End of the Med Optimization Phase Inattention Symptoms	23.12 scores on a scale Standard Deviation 3.58	9.77 scores on a scale Standard Deviation 4.44	—	—
Adult ADHD Rating Scale Completed at the End of the Med Optimization Phase Hyperactive/Impulsive Symptoms	17.81 scores on a scale Standard Deviation 5.73	8.00 scores on a scale Standard Deviation 5.08	—	—

Adverse Events

Placebo Arm

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Treatment Arm

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

All Participants in Period 1 Prescribed 30mg

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

All Participants in Period 1 Prescribed 50mg

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

All Participants in Period 1 Prescribed 70mg

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo Arm n=13 participants at risk subjects in this arm treated only with blinded placebo for duration of assessment (period II- between subjects trial).One participant assigned to placebo dropped out before medication was dispensed for period II which is why the side effect data only has a total of 13 and not 14 subjects.	Treatment Arm n=13 participants at risk subjects in this arm (N=13) only treated with blinded optimal dose of LDX (either 30mg, 50mg or 70mg) for duration of assessment (period II between subjects trial).	All Participants in Period 1 Prescribed 30mg n=36 participants at risk During the dose optimization period which occurred before assignment to the placebo arm or treatment arm, all participants were treated with open label medication starting at 30mg of lisdexamfetamine (LDX). Dose was increased weekly (to a max of 70mg) until the optimal dose was defined. Once optimal dose criteria was met, the titration was stopped. Most participants received multiple doses so results for each dose are presented rather than for each participant. All 36 participants who were dispensed the 30mg dose and completed at least one Pittsburgh Side Effect Rating Scale (PSERS) are included in this category.	All Participants in Period 1 Prescribed 50mg n=21 participants at risk During the dose optimization period which occurred before assignment to the placebo arm or treatment arm, all participants were treated with open label medication starting at 30mg of lisdexamfetamine (LDX). Dose was increased weekly (to a max of 70mg) until the optimal dose was defined. Once optimal dose criteria was met, the titration was stopped. Most participants received multiple doses so results for each dose are presented rather than for each participant. 21 of 36 participants were dispensed the 50mg dose.	All Participants in Period 1 Prescribed 70mg n=17 participants at risk During the dose optimization period which occurred before assignment to the placebo arm or treatment arm, all participants were treated with open label medication starting at 30mg of lisdexamfetamine (LDX). Dose was increased weekly (to a max of 70mg) until the optimal dose was defined. Once optimal dose criteria was met, the titration was stopped. Most participants received multiple doses so results for each dose are presented rather than for each participant. 17 of 36 participants were dispensed the 70mg dose.
Psychiatric disorders suicidal ideation	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/11 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/36 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/21 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/17 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Psychiatric disorders self harm attempt	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/11 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/36 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/21 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/17 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.

Other adverse events

Measure	Placebo Arm n=13 participants at risk subjects in this arm treated only with blinded placebo for duration of assessment (period II- between subjects trial).One participant assigned to placebo dropped out before medication was dispensed for period II which is why the side effect data only has a total of 13 and not 14 subjects.	Treatment Arm n=13 participants at risk subjects in this arm (N=13) only treated with blinded optimal dose of LDX (either 30mg, 50mg or 70mg) for duration of assessment (period II between subjects trial).	All Participants in Period 1 Prescribed 30mg n=36 participants at risk During the dose optimization period which occurred before assignment to the placebo arm or treatment arm, all participants were treated with open label medication starting at 30mg of lisdexamfetamine (LDX). Dose was increased weekly (to a max of 70mg) until the optimal dose was defined. Once optimal dose criteria was met, the titration was stopped. Most participants received multiple doses so results for each dose are presented rather than for each participant. All 36 participants who were dispensed the 30mg dose and completed at least one Pittsburgh Side Effect Rating Scale (PSERS) are included in this category.	All Participants in Period 1 Prescribed 50mg n=21 participants at risk During the dose optimization period which occurred before assignment to the placebo arm or treatment arm, all participants were treated with open label medication starting at 30mg of lisdexamfetamine (LDX). Dose was increased weekly (to a max of 70mg) until the optimal dose was defined. Once optimal dose criteria was met, the titration was stopped. Most participants received multiple doses so results for each dose are presented rather than for each participant. 21 of 36 participants were dispensed the 50mg dose.	All Participants in Period 1 Prescribed 70mg n=17 participants at risk During the dose optimization period which occurred before assignment to the placebo arm or treatment arm, all participants were treated with open label medication starting at 30mg of lisdexamfetamine (LDX). Dose was increased weekly (to a max of 70mg) until the optimal dose was defined. Once optimal dose criteria was met, the titration was stopped. Most participants received multiple doses so results for each dose are presented rather than for each participant. 17 of 36 participants were dispensed the 70mg dose.
Nervous system disorders Buccal Lingual Movements	15.4% 2/13 • Number of events 2 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	19.4% 7/36 • Number of events 7 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	28.6% 6/21 • Number of events 6 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	23.5% 4/17 • Number of events 4 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Nervous system disorders picking at skin	15.4% 2/13 • Number of events 2 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	11.1% 4/36 • Number of events 4 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	14.3% 3/21 • Number of events 3 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	5.9% 1/17 • Number of events 1 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Psychiatric disorders anxious/jittery	23.1% 3/13 • Number of events 3 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	23.1% 3/13 • Number of events 3 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	36.1% 13/36 • Number of events 13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	14.3% 3/21 • Number of events 3 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	17.6% 3/17 • Number of events 3 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
General disorders fatigue	15.4% 2/13 • Number of events 2 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	7.7% 1/13 • Number of events 1 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	16.7% 6/36 • Number of events 6 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	9.5% 2/21 • Number of events 2 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	11.8% 2/17 • Number of events 2 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Nervous system disorders headache	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	7.7% 1/13 • Number of events 1 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	36.1% 13/36 • Number of events 13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	28.6% 6/21 • Number of events 6 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	29.4% 5/17 • Number of events 5 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Psychiatric disorders irritability	7.7% 1/13 • Number of events 1 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	23.1% 3/13 • Number of events 3 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	27.8% 10/36 • Number of events 10 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	23.8% 5/21 • Number of events 5 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	23.5% 4/17 • Number of events 4 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Psychiatric disorders depressed mood	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	7.7% 1/13 • Number of events 1 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	13.9% 5/36 • Number of events 5 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	19.0% 4/21 • Number of events 4 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	11.8% 2/17 • Number of events 2 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
General disorders appetite decrease	15.4% 2/13 • Number of events 2 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	23.1% 3/13 • Number of events 3 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	52.8% 19/36 • Number of events 19 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	66.7% 14/21 • Number of events 14 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	70.6% 12/17 • Number of events 12 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
General disorders insomnia	30.8% 4/13 • Number of events 4 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	23.1% 3/13 • Number of events 3 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	30.6% 11/36 • Number of events 11 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	33.3% 7/21 • Number of events 7 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	35.3% 6/17 • Number of events 6 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Musculoskeletal and connective tissue disorders knee pain	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	7.7% 1/13 • Number of events 1 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/36 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/21 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/17 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Endocrine disorders dry mouth	7.7% 1/13 • Number of events 1 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	23.1% 3/13 • Number of events 3 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	30.6% 11/36 • Number of events 11 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	38.1% 8/21 • Number of events 8 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	70.6% 12/17 • Number of events 12 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Gastrointestinal disorders stomachache	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	16.7% 6/36 • Number of events 6 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	4.8% 1/21 • Number of events 1 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	29.4% 5/17 • Number of events 5 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Psychiatric disorders socially withdrawn	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	8.3% 3/36 • Number of events 3 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/21 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/17 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.
Nervous system disorders motor tic	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/13 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/36 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	0.00% 0/21 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.	11.8% 2/17 • Number of events 2 • Adverse event data reported for period II (mean duration 8 weeks). While 27 total subjects were randomized to a treatment arm (med vs.placebo), 1 withdrew before med was dispensed which is why we have side effect data for 26 and not 27. Pittsburgh Side Effect Scale (PSERS) was given at every visit to all participants to measure adverse events. It contains 13 items measured medication side effects from 0 (none) to 3 (severe). The Columbia-Suicide Severity Rating Scale (C-SSRS) measured suicide risk. It was given at every visit. Both measures were self completed.

Additional Information

Dr. James Waxmonsky

Florida International University

Phone: 717 531 8646

Email: jwaxmons@fiu.edu

Results disclosure agreements

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