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?