Study Design for a Randomized Controlled Trial of Osmotic-Release Methylphenidate (OROS-MPH) Osmotic-Release Methylphenidate (OROS-MPH) for Attention Deficit Hyperactivity Disorder for Attention Deficit Hyperactivity Disorder in Adolescents with Substance Use Disorders in Adolescents with Substance Use Disorders June 14, 2006, Pharmacological Treatment of ADHD in Substance-Abusing Adolescents and Adults: New Findings, Research Directions, and Clinical Implications: 3:10 – 3:30 Presenter: Theresa Winhusen, Ph.D.

Principal Investigators Principal Investigator –Paula Riggs MD University of Colorado at Denver & Health Sciences Center (UCDHSC) Co-Principal Investigators –Theresa Winhusen PhD –Robert Davies MD, Medical Co LI (UCDHSC) Principal Investigator –Paula Riggs MD University of Colorado at Denver & Health Sciences Center (UCDHSC) Co-Principal Investigators –Theresa Winhusen PhD –Robert Davies MD, Medical Co LI (UCDHSC)

Background & Significance  30-50% of adolescents in substance treatment have ADHD  ADHD associated with:  More severe substance abuse  Worse behavior problems  Poorer treatment outcomes  30-50% of adolescents in substance treatment have ADHD  ADHD associated with:  More severe substance abuse  Worse behavior problems  Poorer treatment outcomes

Integrated treatment is considered to be a core drug treatment principle (NIDA, 1999) Recent community treatment survey  < 50% had “dual diagnosis” programs  Of those with dual diagnosis programs: 43.4% did not offer prescription meds 37.8% did not offer psychiatric/psychological evaluation Motjabai, 2004 Integrated treatment is considered to be a core drug treatment principle (NIDA, 1999) Recent community treatment survey  < 50% had “dual diagnosis” programs  Of those with dual diagnosis programs: 43.4% did not offer prescription meds 37.8% did not offer psychiatric/psychological evaluation Motjabai, 2004 Background & Significance

  One RCT targeting ADHD in adolescents with co- occurring SUD   12 week trial pemoline* n=69, adolescents   Similar safety, efficacy for ADHD as in adolescents without SUD   No impact on drug use in the ABSENCE of specific substance treatment Riggs et al 2004 *Schedule 1V psychostimulant Background & Significance

Treatment of ADHD +/- SUD Treatment of ADHD +/- SUD Schedule II psychostimulants, gold standard  Non-scheduled alternatives-- bupropion and atomoxetine-- have lower effect sizes (.5 and.7) OROS-MPH/Concerta  Long acting (12 hours); once daily dosing  Equivalent efficacy to short acting psychostimulants  Controlled delivery system likely reduces abuse potential Schedule II psychostimulants, gold standard  Non-scheduled alternatives-- bupropion and atomoxetine-- have lower effect sizes (.5 and.7) OROS-MPH/Concerta  Long acting (12 hours); once daily dosing  Equivalent efficacy to short acting psychostimulants  Controlled delivery system likely reduces abuse potential

Standardized SUD Treatment  Individual Manualized Cognitive Behavioral Therapy (CBT)  Found effective for SUD in adolescents  Individual, not group, due to feasibility  16 sessions, including up to 3 family sessions

Study Objectives Primary Objectives  1a Evaluate safety and efficacy of OROS- MPH vs. Placebo for ADHD in adolescents with SUD  1b Evaluate impact of treatment of ADHD with OROS-MPH on substance treatment outcomes

Study Design 16-week randomized controlled trial  OROS-MPH (72mg/day) vs placebo  CBT for SUD  Weekly  Outpatient Power  N= 300 to detect low/medium effect size (.4)  11 study sites

Study Sites  Wave 1 LRADAC, South Carolina LRADAC, South Carolina Synergy, Colorado Synergy, Colorado STARR, Northern New England STARR, Northern New England  Wave 2 Operation PAR, Florida Operation PAR, Florida Gateway, Florida Gateway, Florida Mountain Manor, Mid-Atlantic Mountain Manor, Mid-Atlantic Crittenton, Ohio Valley Crittenton, Ohio Valley St Lukes Roosevelt, Long Island St Lukes Roosevelt, Long Island MHMR of Tarrant County, Texas MHMR of Tarrant County, Texas Rehab After Work, Delaware Valley Rehab After Work, Delaware Valley Addiction Medicine Services, Appalachian Tri State Addiction Medicine Services, Appalachian Tri State

Study Participants Participants  Inclusion  Adolescents (13-18)  DSM IV ADHD  At least one SUD  Exclusion  serious medical illness  bipolar  psychosis  opiate dependence  methamphetamine abuse, dependence  other treatment; psychotropics

Primary Outcome Measures  DSM-IV ADHD Symptom Checklist  Number of Use Days Substance Use Self-Report using the TLFB -Substance Use Self-Report using the TLFB

Other Efficacy Measures ADHD  Clinician Global Impression of Improvement (CGI-I) Rating Scale Improvement (CGI-I) Rating Scale Substance Use Outcomes   Frequency of Drug Use (TLFB)  Urine Toxicology Proportion of Negative Urines

Safety Measures  Vital Signs/Weight  Pregnancy Test  Adverse Events  Prior/Concomitant Medications  Lab values (urinalysis, CBC, LFTs)

  Wave 1 Sites InitiatedMarch 2006   Wave 2 Site InitiationJune-July 2006   Wave 1 Sites InitiatedMarch 2006   Wave 2 Site InitiationJune-July 2006 Study Progress

Study Progress - Wave 1

Referral Sources - Wave 1

Pre-Screen Ineligibility-Wave 1

Medication Tolerability - Wave 1

2006 A/4 M/5 J/6 J/7 A/8 S/9 O/10 N/11 D/ J/1 F/2 M/3 A/4 M/5 J/6 J/7 A/ S/9 O/10 N/11 D/12 S/9 O/10 N/11 D/ J/1 F/2 M/3 A/ A/4 M/5 J/6 J/7 A/8 S/9 O/10 N/11 D/ J/1 F/2 M/3 A/4 M/5 J/6 J/7 A/ S/9 O/10 N/11 D/12 S/9 O/10 N/11 D/ J/1 F/2 M/3 A/4 Study Timeline & Enrollment Schedule midpoint enrollment completed F/u study completionStudy close out, data lock, manuscript preparation Initial projection enrollment completion 16 wk study completion