Transcript ADHD Medication Abuse Potential - Catherine Martin

ADHD Medication Abuse Potential:
the Drug and/or the Patient
CAPTASA
January 29, 2008
Catherine A. Martin, MD
University of Kentucky College of
Medicine; Department of Psychiatry
[email protected]
ADHD Medication Abuse Potential:
the Drug and/or the Patient

Characteristics of Drugs with Abuse Liability

Patient at risk for stimulant misuse

Two Stimulants:Therapeutic Stimulants and
Nicotine: Patient and the Drugs

Where do we go from here: Clinicians?,
Researchers?
Why are we concerned about abuse
of therapeutic stimulants?

Frequent reports of misuse of stimulants in
ADHD patients

College Stimulant Diversion: Study Drugs and
more
NOTE: stimulant misuse in those who are being
medically treated for ADHD is more likely in those
who are not diagnosed and treated for ADHD until
high school.
Accumbens
1100
1000
900
800
700
600
500
400
300
200
100
0
AMPHETAMINE
DA
DOPAC
HVA
250
NICOTINE
200
Accumbens
Caudate
150
100
0
0
1
2
3 hr
Accumbens
COCAINE
DA
DOPAC
HVA
300
200
100
0
5 hr
250
% of Basal Release
1
2
3
4
Time After Amphetamine
% of Basal Release
400
0
% of Basal Release
% of Basal Release
Effects of stimulants on dopamine levels
0
1
2
3
4
Time After Cocaine
Accumbens
5 hr
ETHANOL
Dose (g/kg ip)
200
0.25
0.5
1
2.5
150
100
0
Time After Nicotine
Source: Di Chiara and Imperato
0
1
2
3
Time After Ethanol
4hr
Availability: Methylphenidate
and Amphetamine Prescriptions
Source:IMS Health,National Prescription Audit PlusTM
Adult Studies in Adult Addicts
Study in Early Adolescents with ADHD

24 youth with current or past histories of
therapeutic stimulant use

Ages 11-15 (12.93 + 1.41)

Females: 54%

24 Caucasian, 4 African-American, 1 biracial
Laboratory Study: A View to the
Challenges

Two 5-hour sessions

Minimum of 48 hour between sessions

Double blind, placebo controlled, randomized

Methylphenidate (0, 0.25 mg/kg)

Daily meds were withheld until after the session
Measures: Laboratory Study

Self-report effects: VAS & ARCI

Cardiovascular Effects: BP, HR

Task Performance: CPT

Activity Measure: Actometer
Experimental Day

0800 Arrives

0805 Blood draw

0815 Breakfast

0825 Assessment

0910 Drug Administration

1005 Assessment

1105 Assessment

1205 BP, HR, and VAS

1210 Sack Lunch and Return to School
VAS

.
Not at all Extremely
Able to Concentrate.
Not at all Extremely
Sleepy
Not at all Extremely
How sure are you that you got the medication today?
MBG=Euphoria

Today I say things easily.

Things around me seem nicer than usual.

I have a good feeling in my stomach.

I feel I will lose the happiness that I have now.

I feel happy with the world and people around me.

I can completely understand what other people are saying
when I feel the way I do now.
ARCI
C: ARCI A-Scale
D: ARCI MBG Scale
10
12
10
8
8
6
6
4
4
2
2
0
0
0
1
Hours Post Dose
2
0
1
Hours Post Dose
2
VAS
Sensation-Seeking

Personality factor
-Seek complex sensations and
experiences
-Take risks for the sake of such
experiences
-Susceptibility to boredom
-Disinhibition
Sensation Seeking and Drug Use

Is associated with drug use across the
life cycle: both amount and how early

It increases in adolescence and
declines in middle age

Prevention efficacy
Attitude and Interest Survey
Strongly
Disagree
Disagree
Uncertain
Agree
Strongly
Agree
I would like to explore strange places.
I like wild parties.
I like to do frightening things.
I get restless when I spend too much time at home.
I would like to take off on a trip with no pre-planned routes or
timetables.
I would like to try bungee jumping.
I would like to have new and exciting experiences, even if I have to
break the rules.
I prefer friends who are excitingly unpredictable.
SS study in Young Adults

Healthy adults, 18-21

Occasional stimulant and sedative users

Two groups: High- and Low-Sensation
Seekers
-Modified Zuckerman Sensation-Seeking Scale
(Form V)
-Top and bottom third of cohort over 4 annual
assessments between 6th and 10th grades
VAS: Feel Drug Effect
Low Sensation-Seekers
50
40
High Sensation-Seekers
50
A mphet amine
( mg/ 7 0 kg)
0.0
7.5
15.0
40
30
30
20
20
10
10
0
0
0
1
2
3
Hour Post Dose
0
1
2
3
VAS: Like Drug
Low Sensation-Seekers
50
High Sensation-Seekers
50
A mphet amine
( mg/ 7 0 k g)
0.0
7.5
15.0
40
40
30
30
20
20
10
10
0
0
0
1
2
3
Hour Post Dose
0
1
2
3
ADHD + …. Another at Risk Group

Depression (not just
demoralization) (9-38%),

Anxiety Disorders (25%)
including OCD

Oppositional Defiant Disorder
or Conduct Disorder (50%)
Biederman and Faraone
Association of ADHD w/ Nicotine Use
ADHD Adolescents have:
•
Higher rates of smoking (Hartsough and Lambert, 1987;
Barkley et al., 1990; Milberger et al., 1997)
•
Earlier onset of smoking (Wilens et al., 1997, Lambert and
Hartsough, 1998)
•
Greater levels of nicotine dependence
Hartsough, 1998)
(Lambert and
Modafinil

Original indications was for narcolepsy

An adjunct in the treatment of depression

Cocaine dependence (Dackis et al., 2005)

Low abuse liability (Gold and Balster, 1996; Stoops et
al., 2005)
Modafinil
•
Modafinil potentially meets several criteria for
pharmacotherapy (Stitzer and Walsh, 1997)
•
It may alleviate post cessation withdrawal
symptoms
•
It may also address some predisposing
symptoms related to initiation and maintenance
of nicotine use, specifically inattention and
depression
Hungry
Hungry
Nicotine (0 mg)
Nicotine (7 mg)
Nicotine (14 mg)
5.5
5.5
5.5
4.5
4.5
4.5
3.5
3.5
3.5
2.5
2.5
2.5
1.5
1.5
1.5
0.5
0.5
0.5
2
3
4
2
3
4
Time (hours post dose)
2
3
4
Modafinil
0 mg
100 mg
200 mg
CPT
110
0 mg
200 mg Modafinil
400 mg Modafinil
Correct Hits
105
100
95
90
85
80
75
70
0.0
1.0
1.5
2.0
2.5
Time (Hours Past Dose)
3.0
Stimulant Misuse
Is more likely in those who are not diagnosed and treated for
ADHD until high school, and may suggest two possibilities.
1. Under- or late-treated ADHD increases the risk for high
risk behavior, including drug diversion.
2. Late-diagnosed ADHD may represent a different symptom
cluster or associated co-morbidities that are associated
with increase in high risk behaviors such as Sensation
Seeking or Conduct Disorder
In the clinic…

It is essential that stimulants only be
prescribed for well documented disorders.

Clinicians who prescribe stimulants
(pediatricians, child psychiatrists, family
physicians, neurologists) should inform their
patient on the risk of diversion of medication.
In the clinic…

Although stimulants are first line treatment of
ADHD, and do not appear to escalate other
drug use (nicotine use not known at this time)

Whether or not they should be first line
treatment for ADHD patients with comorbidities that suggest high-risk behaviors is
not known
In the clininc

Patients and if appropriate their parents
should be informed that the patient may be
pressured to share or sell their stimulants.

Likewise adolescents, who are not being
treated for ADHD, should be warned about
the risks of drug use including misused
stimulants.
In the clinic…
Similar to safety communication given in the
pediatricians’ office regarding keeping
medications out of the reach of children,
adolescents and young adults should be
advised to keep their stimulant medication
under lock and key. Parents and physicians
should be carefully monitoring numbers of
pills and times needed by the patient.