Shire SCT: Lisdexamfetamine Treatment for ADHD and SCT

Sluggish Cognitive Tempo (SCT) describes individuals who are dreamy, spacey, slow moving,
hyper active, have difficulty initiating tasks, and often seem under-motivated and
under-aroused. Barkley identified nine cardinal symptoms of SCT: 1) prone to daydreaming
instead of concentrating; 2) trouble staying alert/awake in boring situations; 3) being
easily confused; 4) being easily bored; 5) feeling spacey/in a fog; 6) frequently feeling
lethargic; 7) being under-active/having less energy than others; 8) being slow moving; 9) not
processing information quickly/accurately. Individuals were identified as SCT if they had at
least 5 of 9 symptoms rated often or very often on the 9-item SCT subscale from the Barkley
Adult ADHD Rating Scale-IV: Self-Report (BAARS-IV; hereafter called the Barkley SCT Scale).

This is a 2 Site (NYU and Mount Sinai) Study of LDX in 50 adults with Attention Deficit
Disorder (ADHD) and Sluggish Cognitive Tempo (SCT). The study will be a double-blind,
10-week, cross-over treatment trial of LDX (4 weeks; 30 - 70 mg/day) vs. placebo (4 weeks)
with an intervening single- blind placebo washout period (2 weeks). During the LDX treatment
period, LDX treatment will be initiated at a dose of 30mg/day at Visit 0 and can be titrated
up (in the judgment of the investigator) in increments of 20mg, based upon clinical response
and tolerability, to 50mg/day at Visit 1 and 70mg/day at Visit 2. Subjects receiving daily
doses of 50mg or 70mg of LDX will be allowed to down titrate one dosage step of 20mg during
Visits 2-4 if (in the judgment of the investigator) they are having issues in tolerability.
The highest effective dose of LDX will then be maintained until Visit 4. Patients will be
seen weekly throughout the trial except during placebo washout.

Inclusion Criteria:

1. Male or female between the ages of 18-60 of all races and ethnicity.

2. Meets DSM-IV-TR criteria for a primary diagnosis of inattentive or combined type ADHD
as diagnosed via the Adult ADHD Clinician Diagnostic Scale

3. For the Sluggish Cognitive Tempo+ group Must Score ≥ 5 items on the Barkley Sluggish
Cognitive Tempo Scale; Must be rated 3 ("often") or ("very often") and total Sluggish
Cognitive Tempo symptom score ≥ 26; must have a T-score ≥ 65 on the Metacognition
Index and Motivation Subscales of the Behavior RatingInventory of Executive Function -
Adult Version (BRIEF-A)

4. Impairment: must have a total score > 95th percentile on the Barkley Functional
Impairment Rating Screen (Barkley Functional Impairment Scale (BFIS).

5. For the Sluggish Cognitive Tempo - group, < 5 items on the Barkley SCT Scale must be
rated 3 ("often") or 4 ("very often") and total SCT symptom score < 26; must have a
T-score < 65 on the Metacognition Index and Motivation Subscales of the BRIEF-A.

Exclusion Criteria:

1. Meets DSM-IV-TR criteria for a primary diagnosis of hyperactive-impulsive type ADHD.

2. Any other current psychiatric disorder, determined via the M.I.N.I , which requires
pharmacotherapy treatment.

3. Current suicidal ideation or history of suicide attempts, based on the Columbia-
Suicide Severity Rating Scale(C-SSRS).

4. Lifetime history of bipolar disorder or any psychotic disorder as per the M.I.N.I

5. Pregnant, breastfeeding or women planning to become pregnant.

6. Positive urine drug toxicology are excluded.