Subtypes of ADHD Related to Substance Use Subtypes of ADHD Related to Substance Use Disorders (SUD): Results from the MGH Disorders (SUD): Results from the MGH Longitudinal Study of Boys with ADHDLongitudinal Study of Boys with ADHD
Timothy E. Wilens, MDMassachusetts General Hospital
Harvard Medical School
Funding: NIDA RO1 DA1441 & DA 11929 (TW)
Disclosures Disclosures
Dr. Wilens has served as a consultant, speaker, or has received grant support from the following
NIH (NIDA, NICMH, NIMH) Abbott, Celltech, Glaxo/SKB, Lilly, McNeil,
Neurosearch, Novartis, Pfizer, Shire
Some of the products discussed are not FDA approved for ADHD or other psychopathology; others may not be FDA approved in the manner discussed (e.g. dosing, patient groups, combination therapy)
ADHD OverviewADHD Overview
ADHD is the most common neurobehavioral disorder presenting for treatment in youth
Prevalence: 6-8% youth worldwide; 4% of adults Associated with impairment in multiple domains Majority with comorbid learning disabilities &
psychiatric comorbidity including conduct disorder
Treatment includes educational, psychotherapeutic, and psychopharmacological interventions
(Goldman, JAMA:1998; Wilens et al Ann Rev Med, 2002;
Faraone et al., World Psych; 2003; Kessler et al, APA 04)
ADHD SubstanceAbuse/Dep
Excessive overlap of ADHD in SA ADHD±comorbidity is a risk factor for SA
Overlap Between ADHDOverlap Between ADHDand Substance Use Disorders (SUD)and Substance Use Disorders (SUD)
(Wilens et al., Psych Clin N Am: 2004)
Smoking in ADHD Adolescents (Mean 15 years)Smoking in ADHD Adolescents (Mean 15 years)
0
5
10
15
20
All ADHD Controls
%Smoking
p<0.003vs cntrls
24 11
(Millberger et al., JAACAP 1997)(Millberger et al., JAACAP 1997)
(Conduct Disorder accounting for differences)
Onset of Substance Abuse in ADHD AdultsOnset of Substance Abuse in ADHD Adults(Retrospectively Derived)(Retrospectively Derived)
0 10 20 30 40 50 600.0
0.2
0.4
0.6
0.8
1.0ADHDControl
Age of Onset
Prob
abili
ty
Wilens TE, et al. J Nerv Ment Dis. 1997;185(8):475-482.
**p<.05 vs control
Lifetime Rates of SUD Lifetime Rates of SUD in Controlled Longitudinal Studies of ADHD Adultsin Controlled Longitudinal Studies of ADHD Adults
0%5%
10%15%20%25%30%35%40% ADHD Control
Mean age range at follow-up: 18-26 yearsMean age range at follow-up: 18-26 yearsTotal ADHD N=845, total Control N=1085Total ADHD N=845, total Control N=1085
% w
ith S
UD
( from Wilens et al., Psych Clin N Am: 2004)
SUD in Young Adults with ADHDSUD in Young Adults with ADHD
Methods Male subjects ascertained from an ongoing
longitudinal family study of ADHD. Case matched controls (at baseline) Data obtained from year 10 Diagnosis(es) by KSADS/SCID Raters blinded to ascertainment
(Wilens et al., APA 2004)
SUD in Young Adults with ADHDSUD in Young Adults with ADHDSUD Monitoring
Subjective measures• Drug use severity index1
• Self-report measure• Items including frequency and severity (problem)• Items relative to initiation and continuation
• Module from DSM on SA• Semi-structured interview• Direct report of proband to interviewer• Indirect report of parent to interviewer• Best estimate diagnosis
Objective measures• Urine by radioimmunoassay (RIA)-hospital analysis
including osmolality
1. Tarter RE, Hegedus AM. Alcohol Health Res World. 1991;15:65-73.
Nicotine Use in Male Probands at 10 year Follow-Nicotine Use in Male Probands at 10 year Follow-up (Age 21 yrs), up (Age 21 yrs),
Any UseAny Use
73
45
0
10
20
30
40
50
60
70
80
90
100
%
*p=0.039 vs. No Use, controlling for SES and Conduct Disorder (Wilens et al., APA 2004)
*p=0.039
ADHD Control
Nicotine Use in Male Probands at 10 year Follow-Nicotine Use in Male Probands at 10 year Follow-up (Age 21 yrs), up (Age 21 yrs),
Stratified by Frequency of UseStratified by Frequency of Use
18
56
18
27
0
10
20
30
40
50
60
70
80
90
100
Moderate Use (1-10x/yr) Heavy Use (>11x/yr)
ADHD Control
%
OR=3.2*p=0.04
(Wilens et al., APA 2004)
Nicotine Use in Male Probands at 10 year Follow-Nicotine Use in Male Probands at 10 year Follow-up (Age 21yrs), up (Age 21yrs), Stratified by Comorbidity with Stratified by Comorbidity with
Conduct Disorder (CD)Conduct Disorder (CD)
75
6370
44
0
10
20
30
40
50
60
70
80
90
100
ADHD Control
CD No CD
%
*p=0.359
*p=0.141
(Wilens et al., APA 2004)
Marijuana Use in Male Probands at 10 year Marijuana Use in Male Probands at 10 year Follow-up, Follow-up,
Any UseAny Use
69
50
0
10
20
30
40
50
60
70
80
90
100
%
*p=0.04 vs. No Use, controlling for age, SES and Conduct Disorder (Wilens et al., APA 2004)
p=0.04
ADHD Controls
Marijuana Use in Male Probands at 10 year Marijuana Use in Male Probands at 10 year Follow-up, Follow-up,
Stratified by Frequency of UseStratified by Frequency of Use
29
40
19
31
0
10
20
30
40
50
60
70
80
90
100
Moderate Use (1-10x/yr) Heavy Use (>11x/yr)
ADHD Control
% OR=2.7*p=0.114
(Wilens et al., APA 2004)
Marijuana Use in Male Probands at 10 year Marijuana Use in Male Probands at 10 year
Follow-up, Follow-up, Stratified by Comorbidity with Conduct Disorder Stratified by Comorbidity with Conduct Disorder
(CD)(CD)
67 70
89
43
0
10
20
30
40
50
60
70
80
90
100
ADHD Control
CD No CD
%
*p=0.801 *p=0.012
(Wilens et al., APA 2004)
Reason for First Use of Preferred Drug:Reason for First Use of Preferred Drug:To Get HighTo Get High
65
50
0
10
20
30
40
50
60
70
80
90
100
ADHD Control
%
OR=2.0*p=0.1
*p=0.1 controlling for age, SES and Conduct Disorder(Wilens et al., APA 2004)
Reason for First Use of Preferred Drug:Reason for First Use of Preferred Drug:To Change MoodTo Change Mood
58
40
0
10
20
30
40
50
60
70
80
90
100
ADHD Control
%
OR=2.8*p=0.058
*p=0.058 controlling for age, SES and Conduct Disorder (Wilens et al., APA 2004)
Reason for First Use of Preferred Drug:Reason for First Use of Preferred Drug:To Sleep BetterTo Sleep Better
17
7
0
10
20
30
40
50
60
70
80
90
100
ADHD Control
%
OR=5.4*p=0.061
*p=0.061 controlling for age, SES and Conduct Disorder(Wilens et al., APA 2004)
Continued Use of Preferred Drug:Continued Use of Preferred Drug:To Get HighTo Get High
69
56
0
10
20
30
40
50
60
70
80
90
100
ADHD Control
%
OR=1.7*p=0.316
*p=0.316 controlling for age, SES and Conduct Disorder(Wilens et al., APA 2004)
Continued Use of Preferred Drug:Continued Use of Preferred Drug:To Change MoodTo Change Mood
64
43
0
10
20
30
40
50
60
70
80
90
100
ADHD Control
%
OR=2.4*p=0.121
*p=0.121 controlling for age, SES and Conduct Disorder(Wilens et al., APA 2004)
Continued Use of Preferred Drug:Continued Use of Preferred Drug:To Sleep BetterTo Sleep Better
29
7
0
10
20
30
40
50
60
70
80
90
100
ADHD Control
%
OR=5.7*p=0.03
*p=0.03 controlling for age, SES and Conduct Disorder(Wilens et al., APA 2004)
(Wilens TE. Psych Clin N Am: 2004).
Apparent ages of risk for SUD related to ADHD and Apparent ages of risk for SUD related to ADHD and ADHD comorbidity (BPD, CD, BPD+CD)ADHD comorbidity (BPD, CD, BPD+CD)
Age of SA onset• Comorbid ADHD: 12-16 years• Noncomorbid ADHD: 17-22 years
• Females earlier onset than males• ADHD impact starts approximating
comorbidity• “Start talking about it in 10-12 year olds”
Cigarette use• 50% of stable cigarette users with ADHD
manifest SUD
MGH Longitudinal Study of ADHDMGH Longitudinal Study of ADHDMedication QuestionnaireMedication Questionnaire
Query of medication use Pilot data Seven questions regarding appropriate use of
prescribed medications Self-report on those who were taking meds Not psychometrically validated
Longitudinal study of ADHD (and controls)10 year follow-up data (mean age 19 years) Data available on 55 ADHD and 43 controls Psychopathology by KSADS (baseline)
MGH Longitudinal Study of ADHDMGH Longitudinal Study of ADHDMedication QuestionnaireMedication Questionnaire
Have you sold the medication prescribed by your doctor?
Have you used more of your medication than you were supposed to?
Have you gotten high on your medication?
Have you misused your medication?
(continued)
MGH Longitudinal Study of ADHD MGH Longitudinal Study of ADHD Medication QuestionnaireMedication Questionnaire
(continued)(continued)
Have you not taken your medication so that you could use drugs or alcohol?
Have you used alcohol or drugs on the days you take your medication?
Have you had a reaction to drugs or alcohol while taking your medication?
Sold Prescribed MedicationSold Prescribed Medication
0
10
20
30
40
50
%
ADHD (N=55) Control (N=43)
p=0.025
11%0%
Misused MedicationMisused Medication
0
10
20
30
40
50
%
ADHD (N=55) Control (N=43)
p=0.006
22%
2%
Used More MedicationUsed More Medication
0
10
20
30
40
50
%
ADHD (N=55) Control (N=43)
p=0.018
22%
5%
Gotten High From MedicationGotten High From Medication
0
10
20
30
40
50
%
ADHD (N=55) Control (N=43)
p=0.414
9%5%
Skipped Medication to UseSkipped Medication to UseAlcohol or DrugsAlcohol or Drugs
0
10
20
30
40
50
%
ADHD (N=55) Control (N=43)
p=0.027
16%
2%
Used Medication with Alcohol or DrugsUsed Medication with Alcohol or Drugs
0
20
40
60
80
100
%
ADHD (N=55) Control (N=43)
p=0.6
31%26%
Reaction to Alcohol or Drugs with MedicationReaction to Alcohol or Drugs with Medication
0
5
10
15
20
25
%
ADHD (N=55) Control (N=43)
p=0.125
5%0%
Diverting medication… Who is at risk?Diverting medication… Who is at risk?
0
10
20
30
40
50
% o
f M
edic
ated
Sub
ject
s
ADHD (N=55) SUD (N=48) Conduct (N=21)
11% 10%14%
Diversion of Medications and ADHD ComorbidityDiversion of Medications and ADHD Comorbidity
0
20
40
60
80
100
% o
f M
edic
ated
S
ubje
cts
ADHD+SUD ADHD+Conduct ADHD+SUD orConduct
83% 83%
100%
Misuse of Medication… Who is at risk?Misuse of Medication… Who is at risk?
0
10
20
30
40
50
% o
f M
edic
ated
Sub
ject
s
ADHD (N=55) SUD (N=48) Conduct (N=21)
22% 21%
14%
Misuse of Medication and ADHD ComorbidityMisuse of Medication and ADHD Comorbidity
0
20
40
60
80
100
% o
f M
edic
ated
S
ubje
cts
ADHD+SUD ADHD+Conduct ADHD+SUD orConduct
75%
59%
83%
Diversion and Misuse of Medications in ADHDDiversion and Misuse of Medications in ADHD
All cases receiving immediate-release stimulants
• Methylphenidate
• Amphetamine No evidence of diversion or misuse of
• Extended-release stimulants (e.g. OROS MPH)
• Nonstimulants (TCA, bupropion, clonidine)
LimitationsLimitations
Relatively small sample size Especially for med questionnaire
Data generalize to males only Data from “middle class” sample Data presented today based on self
report Medication questionnaire not
psychometrically validated Other comorbidities and mediators of
SUD not examined for these analyses
Summary: ADHD+Substance AbuseSummary: ADHD+Substance Abuse ADHD is a risk factor for Cigarette Smoking ADHD is a risk factor for any and heavy substance use
Adolescent-onset clearly linked to conduct disorder (and Bipolar disorder) Later onset probably more linked to ADHD
Evidence of self medication Attenuation of mood Soporiphic effects of medication
Evidence of diversion and misuse of immediate release stimulant medication in ADHD High risk groups (those with ADHD+SUD+Conduct) Need to discuss proper storage and use of medications
QUESTIONS?QUESTIONS?
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