Common Sense Strategies For Prescribing ADHD Medication

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Special Needs Ministry: www.keyministry.org

Objective: To help participants develop an evidence-based model to guide prescribing decisions for individual patients with ADHD

To meet this objective, participants will:

Capone NM, McDonnell TP. Presented at the APA Annual Meeting, Toronto, ON (2006)

Patie

nts

(%)

ADHD Rxs Filled Office Visits

More Frequent Office Visits May Help ADHD Medication Adherence A B

Data shown are the rate (%) of patients with the indicated number of office visits or prescriptions filled over the 12-month study period.

Patie

nts

(%)

Grcevich S, et al. Presented at: AACAP Annual Meeting, San Diego, CA, October 27, 2006.

Capone N, et al. Presented at the CHADD International Conference (2005) Dallas, TX.

Monthly Persistence With OROS-MPH (N=2398) %

of P

atie

nts

Capone N, et al. Presented at the CHADD International Conference (2005) Dallas, TX.

Monthly Persistence With MAS-XR (N=1626)

0% 10% 20% 30% 40% 50% 60% 70% 80% 90%

100%

Sep-03 Oct-03 Nov-03 Dec-03

MAS-XR Category Jan-04 Feb-04 Mar-04 Apr-04 May-04 Jun-04 Jul-04 Aug-04

% o

f Pat

ient

s

Capone N et al. Presented at the CHADD International Conference, Dallas, 2005.

Monthly Persistence With ATX (N=1292)

0%

10% 20% 30% 40% 50% 60% 70%

80% 90%

100%

Sep-03 Oct-03 Nov-03 Dec-03 Jan-04 Feb-04 Mar-04 Apr-04 May-04 Jun-04 Jul-04 Aug-04 ATX Category

% o

f Pat

ient

s

Grcevich S, et al. Presented at: AACAP Annual Meeting, San Diego, CA, October 27, 2006. Wolraich ML, et al. Pediatrics. 2005;115:1734-1746.

Pliszka SR, et al. J Am Acad Child Adolesc Psychiatry. 2006;45:642-657. Pliszka SR, et al. J Am Acad Child Adolesc Psychiatry. 2003;42:279-287.

*TMAP=Texas Medication Algorithm Project

Partial Response or Non-response

Response Partial

Response (if MAS or DEX used in Stage 1)

Algorithm for the Pharmacological Treatment of ADHD (with no significant comorbid disorders), Revised 2005

Stage 0 Diagnostic Assessment and Family Consultation Regarding Treatment

Alternatives

Non-Medication Treatment Alternatives

Response

Continuation

Stage 1A (Optional)

Formulation not used in Stage 1

Stage 1

Any stage(s) can be skipped depending on the clinical picture

Stimulant not used in Stage 1 Stage 2 Partial Response or Non-response

Continuation

Pliszka SR, et al. J Am Acad Child Adolesc Psychiatry. 2006;45:642-657.

DEX = Dextroamphetamine MAS = Mixed amphetamine salts

Methylphenidate or Amphetamine



Response

Response Partial Response (if MAS or

DEX used in Stage 2)


Partial Response

to stimulant or atomoxetine


Response

Response

Stage 3

Continuation

Stage 3A (Optional)

Combine stimulant and atomoxetine

Continuation

Stage 2A (Optional)

Formulation not used in Stage 2

Bupropion or TCA Stage 4

Stage 2 Stimulant not used in Stage 1

TCA = Tricyclic antidepressant

Atomoxetine


Response

Response



Stage 4

Continuation

Continuation

Clinical Consultation

Stage 5

Stage 6

Maintenance

Bupropion or TCA

Agent not used in Stage 4

Alpha agonist


Factors in Selecting Medication for Individual ADHD Patients:

Grcevich S. Future Neurology 2006; 1(5) 525-534 Pliszka SR et al. J Am Acad Child Adolesc Psychiatry 2006;45(6):642-657.

Approved stimulant products for ADHD:

Immediate- Release

Stimulants

Long-Acting, Formulated Stimulants

Non- Stimulants

Long-Acting, Prodrug

Stimulants

Amphetamine Amphetamine SR Atomoxetine Lisdexamfetamine dimesylate

D-methylphenidate Dexmethylphenidate XR

Methylphenidate Methylphenidate CD

Mixed amphetamine salts Methylphenidate LA

Methylphenidate patch

Mixed amphetamine salts XR

OROS* methylphenidate

*OROS=osmotic release oral system

Faraone 2006 Metanalysis (29 controlled studies, 4465 children,

adolescents)

Amphetamine 0.92

Methylphenidate 0.80

Atomoxetine 0.73

Modafinil 0.49

Buproprion 0.32

Faraone SV, Spencer TJ: Presented at APA Annual Meeting, Toronto, Canada (2006)

Perc

ent R

espo

nse

to

Tre

atm

ent

Michelson, D. Presented at AACAP Annual Meeting, Washington, DC, October 21, 2004

*P<0.05; †P<0.0001 compared with baseline by 1-sample t test. ‡ P<0.0001 MAS-XR compared with ATX by ANCOVA.

‡

–0.74† –0.81†

–0.86† –0.78†

–0.47†

0.33†

*

Wigal et al. Poster presented at the 157th Annual Meeting of the American Psychiatric Association, New York, May 4, 2004.

‡ ‡ ‡ ‡

Arnold et al. J Attention Dis 2000;3:200-211.

Best response (percent)

Meta-Analysis of Within-subject Comparative Trials Evaluating Response to Stimulant Medications

AMP=amphetamine MPH=methylphenidate

28%

16%

41%

Implications of Arnold Study:

Arnold LE et al. Arch Gen Psychiatry, 1976;33(3):292-301

James RS et al. J Am Acad Child Adolesc Psychiatry 2001;40(11):1268-76

LDX vs. MAS-XR in Children: SKAMP LS Mean Across Assessment Day – ITT

Population

Biederman J. et al. Poster presented at Annual APA Meeting, May 24, 2006, Toronto, Ontario, Canada

Deportment (primary endpoint) Inattention

Mean

Sco

re

3 – – –

– 2 –

– –

– 1 –

– – –

0 –

LDX

MAS-XR

Placebo

*** p<0.001 compared to placebo

*** ***

*** ***

OROS-MPH/MPH Patch Parallel Group Study:

* *

* P < .0001 vs placebo. Study was not powered for comparison between transdermal and OROS MPH. Findling and Lopez. Poster presented at the AACAP Annual Meeting. Toronto. Oct. 20, 2005. N=270

Selecting the Right Delivery System:

Steinhoff K et al. Presented at 53rd Annual Meeting of AACAP, San Diego, CA, October 27, 2006

New Delivery Systems: LDX

Lisdexamfetamine (Prodrug)!

H N!2

O!

N!H!

NH!2

CH!3

l-lysine!

H N!2

O!

OH!

NH!2

+

d-amphetamine (active)!

H N!2

CH!3

Site of cleavage!

Rate-limited!

Hydrolysis!

Maximum Change in Subject Liking Scores after LDX Oral Administration

DRQ-S=Drug Rating Questionnaire-Subject.; *P<.01 vs placebo; †P<.05 vs d-amphetamine Jasinski D, Krishnan S. Poster presentation at US Psychiatric & Mental Health Congress Annual Meeting, New Orleans, Nov 18, 2006.

Placebo LDX 100 mg d-amphetamine 40mg

  Oral administration of 150 mg of LDX produced increases in positive subjective responses that were statistically indistinguishable from the positive subjective responses produced by 40 mg of oral immediate-release d-amphetamine

Mea

n M

axim

um C

hang

e

in D

RQ

-S S

core

s

†

*

Analog classroom study of d-MPH XR: Impact upon math performance

Change From Predose in Number of Math Test Problems Attempted

All P values, d-MPH XR versus placebo. *P<0.001. Pooled data; Studies US08 and US09. Turnbow JM et al. US Psychiatric and Mental Health Conference; 2005; Las Vegas, NV

Change From Predose in Number of Math Problems Correctly Solved

Mea

n C

hang

e Fr

om P

redo

se,

Mat

h C

orre

ct

Hours Postdose

*

* * *

* * * *

* * *

* *

Impr

ovem

ent

Mea

n C

hang

e Fr

om P

redo

se,

Mat

h A

ttem

pted

Hours Postdose

*

* *

* * *

* * *

* *

* *

Impr

ovem

ent

Analog classroom study of OROS MPH: Impact upon math performance

0

5

10

15

20

25

30

35

40

45

50

8:15 9:20 10:30 12:30 14:05 16:00 17:15 18:20 19:10

Placebo OROS MPH (all doses) TID MPH (all doses)

Class period

Change in number of math problems completed

Pelham WE et al. Pediatrics 2001; 107(6) e105.

Laboratory Classroom Mean Change from Pre-Dose in Number of Math Problems Correct

Analog Classroom Study of Transdermal MPH: Impact on Math Performance

Placebo

Transdermal MPH

Patch applied Patch removed

Wigal et al. Poster presented at the AACAP Annual Meeting, Toronto, October 21, 2005.

Impr

ovem

ent

* P < .001 Transdermal MPH vs placebo at all measured post-dose time points.

*

*

* *

* * *

*

N=79

Comparison of Frequently Prescribed Stimulant Preparations:

MAS-XR d,l-AMP 5-30 mg/day

Up to 12 hours

Biphasic release

Rapid onset, effective for ODD, adults

LDX d-AMP 30-70 mg/day

12 hours Prodrug Less appeal to addicts, more consistent duration?

OROS-MPH MPH 18-72 mg/day

12 hours Osmotic release

Prolonged effects on driving

D-MPH XR MPH 5-20 mg/day

12 hours (claimed)

Biphasic release

Rapid onset

Transdermal MPH

MPH 10-30 mg/day

Variable, based on wear time

Patch Potentially longest acting, most flexible duration

Bupropion XL in Adults With ADHD: Percent Responders*

*≥30% reduction from baseline; **p≤0.01, †p<0.05

Wilens T, et al. Biol Psychiatry. 2005;57:793-801.

0

10

20

30

40

50

60

1 2 4 5 8 Time in Study (wk)

Resp

onde

rs (%

) Bupropion XL (N = 81)

Placebo (N = 81)

**

** ** †

Guanfacine in the Treatment of Children with Tic Disorders and ADHD

Scahill L, et al. Am J Psychiatry. 2001;158:1067–1074.

Improvement in Outcome Measures

Measure Guanfacine 0.5-4.5 mg/d

(n =17)

Placebo (n =17)

P-value

ADHD-RS total score 37% 8% <0.001

CGI Global Improvement Scale (rated much improved or very much improved)

47% 0% <0.001

Yale Global Tic Severity Scale total score 31% 0% 0.05   Double-blind, placebo-controlled, parallel design, 8-week study in 34 medication-free youths with ADHD

plus tics; age 7-14   Guanfacine immediate release given TID; maximum allowable dose: 4mg/kg TID   No serious side effects observed; no clinically meaningful cardiovascular changes   One guanfacine discontinuation owing to sedation in week 4

-30 -20 -10

0 10 20 30 40

Placebo 2 mg 3 mg 4 mg

Baseline Endpoint Change in Least

Square (LS)

ADHD-RS: Mean Total Score at Endpoint and Change in LS Mean from Baseline (ITT Population)

*8-week, double-blind, placebo-controlled, parallel-group safety and efficacy study; **p<..001; *** p<.0001 (adjusted Dunnett test compared to placebo following ANCOVA with baseline score as covariate)

** ** ***

Bear Stearns. Presented at London Healthcare Conference, London, March 2004.

Mean

Cha

nge i

n AD

HD-R

S To

tal

Scor

e AD

HD-R

S To

tal

Scor

e

Comorbidity: A Diagnostic Consideration

Lifetime Prevalence of Comorbid Conditions in Pediatric Population With ADHD

Biederman J. J Clin Psychiatry. 2004;65(suppl 3):3-7.

Boys (N = 140) Girls (N = 140)

ODD Enuresis Major

Depression Multiple

(>2) Anxiety

Conduct Disorder

Bipolar Disorder

Correlates of ADHD Among Children in Pediatric and Psychiatric Clinics

Busch et al. Psychiatric Services. 2002;53:1103.

Referral Site

Psychiatric (N=139) %

Pediatric (N=141) %

CD 14 15 ODD 55 45 MDD 50 42 BPD 13 9 Anxiety disorders (≥2)

33 29

SUD* 13 15 Tics 10 6 *SUD includes cigarettes and psychoactive substances.

TMAP Algorithm: Pharmacologic Management of ADHD and Comorbid Depressive Disorder

Pliszka SR et al. J Am Acad Child Adolesc Psychiatry 2006: 45(6) 642-657



TMAP algorithm for pharmacologic management of ADHD and aggression:


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Common Sense Strategies For Prescribing ADHD Medication