Bupropion for ADHD in Adolescents With Substance Use Disorder

Research has shown that bupropion is a safe and effective treatment for both ADHD and
nicotine dependence in individuals without SUD, and newer research provides empirical support
for its unique pharmacotherapeutic properties and potential for treating other addictive
disorders (e.g., methamphetamine dependence, pathological gambling). No controlled studies
have yet evaluated bupropion's safety and efficacy for ADHD and SUD (including nicotine and
cannabis) in adolescents. The lack of research on the safety and efficacy of medications in
adolescents with SUD and psychiatric comorbidities contributes to a serious lack of
integrated treatment for commonly co-occurring mental health and substance problems in
community-based adolescent drug treatment programs. This then contributes to poorer treatment
outcomes and prognosis for the large number of comorbid youths with substance abuse and
mental health problems that significantly impact public health. The specific aims of the
proposed study will address this research gap by conducting a 16-week randomized controlled
trial of bupropion vs. placebo to evaluate the safety and efficacy of this low abuse
potential medication on ADHD, nicotine dependence, and cannabis use disorders (not excluding
other SUD) in 130 adolescents (13-19) receiving concurrent outpatient substance treatment
(CBT). The study design and analytic approach will enable assessment of the complex
inter-relationship between change in ADHD, depression/dysphoria (and other psychiatric
symptoms) and change in nicotine, cannabis and other substance use within and between
treatment groups. Thus, the study addresses important research gaps in at least two priority
areas of the National Institute on Drug Abuse/ National Institutes of Health(NIDA/NIH)
research agenda: 1) research on effective treatments for adolescents with addiction and
psychiatric comorbidity, and 2) medications development research for nicotine and cannabis
use disorders in adolescents.

Inclusion Criteria:

Subjects must 1) be between the ages of 13 and 19, with a parent or legal guardian
available to complete parental assessments for minors; 2) meet DSM-IV diagnostic criteria
for ADHD on the K-SADS-PL; 3) Schedule for Affective Disorders and Schizophrenia score = or
>22 on the DSM-IV ADHD symptom checklist; 4) meet DSM-IV criteria for nicotine dependence
(and/or cut off score of >3 on modified Fagerstrom); 5) meet DSM-IV criteria for cannabis
abuse or dependence on the Kiddie-Sads-Present and Lifetime (K-SADS-PL); 6) have used
marijuana at least 5 of the past 30 days; 7) have used nicotine at least 15 days out of the
past 30 days; 8) be medically healthy; 9) use of effective birth control method if female
and sexually active.

Exclusion Criteria:

Subjects with any of the following will be excluded:1) current or past psychosis; 2)
bipolar I or II disorder; 3) first-degree relative with bipolar I disorder; 4) lifetime
history of seizure disorder; 5) other chronic or serious medical illnesses; 6) lifetime
history of eating disorder; 7) current pregnancy; 8) previous clinically significant
adverse reaction to bupropion; 9) the need to take other psychotropic medications at the
time of study entry. Patients may have had previous psychotherapy or pharmacotherapy for
ADHD or other co-morbidity but cannot have been on psychotropic medication for at least one
month prior to study entry; 10) active participation in substance abuse treatment or mental
health treatment (including outpatient, day-treatment, residential, or inpatient) within 28
days prior to signing consent; 11) non-English speaking (due to the difficulty in
translating the additional materials given to the subjects); 12) cognitively impaired or of
low intelligence;13) breastfeeding; 14) current use of other psychotropic medications
including nicotine replacement therapy; 15) current opiate dependence.