common sense strategies for prescribing adhd medication
DESCRIPTION
This is a 2007 presentation on the topic of how to select medication for patients with ADHD once a diagnosis has been established.TRANSCRIPT
E-mail: [email protected] Web: www.fcbtf.com Phone: 440.543.3400
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
Partial Response or Non-response
Partial Response or Non-response
Response
Response Partial Response (if MAS or
DEX used in Stage 2)
Partial Response or Non-response
Partial Response
to stimulant or atomoxetine
Partial Response or Non-response
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
Pliszka SR, et al. J Am Acad Child Adolesc Psychiatry. 2006;45:642-657.
Response
Response
Partial Response or Non-response
Partial Response or Non-response
Stage 4
Continuation
Continuation
Clinical Consultation
Stage 5
Stage 6
Maintenance
Bupropion or TCA
Agent not used in Stage 4
Alpha agonist
Pliszka SR, et al. J Am Acad Child Adolesc Psychiatry. 2006;45:642-657.
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
Pliszka SR et al. J Am Acad Child Adolesc Psychiatry 2006: 45(6) 642-657
Pliszka SR et al. J Am Acad Child Adolesc Psychiatry 2006: 45(6) 642-657
TMAP algorithm for pharmacologic management of ADHD and aggression:
Pliszka SR et al. J Am Acad Child Adolesc Psychiatry 2006: 45(6) 642-657