Comparison of ADHD Drugs

!"#$%&'()*$+,-.
%/& #271202
!"#$%&'%()*+#,-(./01)2*%3#4)$%$05$/6#5)6$%%
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PHARMACISTS LETTER / PRESCRIBERS LETTER
December 2011
Comparison of Drugs for ADHD

*All ADHD stimulant drugs and Strattera must be dispensed with a Medication Guide*
Stimulants (methylphenidate and amphetamines) are considered first-line agents for the treatment of ADHD based on efficacy and safety. Choose a
product based on dosing, duration, and cost. The chart below can be used as a guide. In about half of cases, patients not responding to one stimulant
may respond to the other.27 When switching to an alternate product, see Dose Conversion Information below, or start with initial dose and titrate.
Some caregivers are uncomfortable with stimulants, and some patients respond poorly to stimulants.27 For these patients, options include atomoxetine
(<*6+**)6+), or extended-release guanfacine or extended-release clonidine.27 Stimulants and atomoxetine are unlikely to increase stroke, heart attacks,
or sudden death.33 But avoid them in patients with serious heart problems, or if blood pressure or heart rate increase would be a problem.37
Regardless of chosen medication, monitor heart rate, blood pressure, height, and weight.27
Products listed in the following chart are FDA-approved for the management of ADHD.a
Abbreviations: AM = morning; bid = twice daily; IR = immediate-release; qid = four times daily; tid = three times daily
Producta Dosage Forms Dosing Frequencyc Duration of Initial and Titration Max Daily
Cost/Monthb Action Dose (every 7 days, Dose
(approx.) unless noted
#
otherwise)g,i
Immediate-release (IR) methylphenidatej
8#*+,#2 (Novartis) 5, 10, 20 mg tabs Given bid to tid (AM, noon, 3 to 5 h27 Initial: 5 mg bid FDA:
(Generics from 4 PM if needed),1,27 preferably (<8 yrs, <25 kg) or 60 mg4
Mallinckrodt, UCB, and $67.43 (10 mg bid) 30 to 45 minutes before meals.4 10 mg bid (>8 yrs,
Watson are AB rated.d >25 kg)1 or for adults
Sandoz product is an 5-10 mg bid or 5 mg Off-label:
authorized generic.h) tid (consider qid)5,31 60 mg;
Titration: Children, 100 mg if
2.5 to 5 mg over 50 kg11
(depending on
weight) per dose AM
and noon; add 4 PM
dose if needed.
Titrate every 7 to 14
days.1 Adults,
5 to 10 mg.5
:.6);%;%;%
Copyright 2011 by Therapeutic Research Center
P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com
(PL Detail-Document #271202: Page 2 of 13)
#
otherwise)g,i
Immediate-release (IR) methylphenidatej (continued)
:)*"=,#2%Chewable Tabs 2.5, 5, 10 mg Given bid to tid (AM, noon, 3 to 5 h27 See 8#*+,#21 See 8#*+,#21
(Shionogi) chewable tabs 4 PM if needed),1,27 preferably
30 to 45 minutes before meals.6
$429.05 (10 mg bid)
:)*"=,#2%Oral Solution 5 mg/5 mL, Given bid to tid (AM, noon, 3 to 5 h7,27 See 8#*+,#21 See 8#*+,#21
(Mallinckrodt) 10 mg/5 mL oral 4 PM if needed),1,27 preferably
(Generic from Tris Pharma is solution 30 to 45 minutes before meals.7
AA rated.)
$429.40 (10 mg bid)
Immediate-release (IR) dexmethylphenidatej

>./+,#2%(Novartis)% 2.5, 5, 10 mg tabs Given bid at least 4 to 5 h9 Initial: 2.5 mg bid FDA:
(Generic from Teva is AB 4 h apart without regard to (children over six 20 mg8
rated.d) $64.94 (5 mg bid) meals.8 years of age and
adults)1 Off-label:
Titration: 50 mg11
2.5 mg with AM
and/or noon dose1
Extended-release (ER) dexmethylphenidatej
>./+,#2%?8e % 5, 10, 15, 20, 25, 30, Given once daily in the morning. 8 to 12 h27 Initial: 5 mg FDA:
(Novartis) 35, 40 mg caps May be taken whole or sprinkled (children over six 30 mg
over applesauce. If sprinkled years of age) or children;
$182.41 (10 mg daily) over applesauce, should be used 10 mg (adults)1 40 mg
immediately and not be stored Titration: 5 mg adults10
for future use. Capsule and/or (children) or 10 mg
capsule content should not be (adults)1 Off-label:
crushed, chewed, or divided.10 50 mg11
:.6);%;%;%
#
otherwise)g,i
Extended-release (ER) methylphenidatej
8#*+,#2%'@e 10, 20, 30, Given once daily in the morning. 6 to 9 h13,27 Initial: 20 mg See 8#*+,#2
(Novartis) 40 mg LA caps May be taken whole or sprinkled (children six years of
Bead-filled capsule (! IR on applesauce. Applesauce age and older and
and ! enteric coated, $157.45 (20 mg daily) should not be warm. If sprinkled adults)1
delayed release) over applesauce, should be used Titration:
immediately and not stored for 10 to 20 mg1,27
future use. Capsule and/or
capsule content should not be
crushed, chewed, or divided.12
8#*+,#2-<8 (Novartis) 20 mg SR tabs Given once daily or bid.1,27 2 to 8 h4,27,L Initial: 20 mg q AM See 8#*+,#2
Wax matrix tab15 Must be swallowed whole.4 for children
(:)*+7+*)%A8 and generics $80 (20 mg daily) tolerating 10 mg IR
from Mallinckrodt and AM and noon, and
Watson are AB rated.d adults1,5
Sandoz product is an Titration: 20 mg;27
authorized generic.h) add 2 PM dose,5 or
add 5 or 10 mg IR
tab in AM and/or at
4 PM1
:)*+7+*)%A8 (UCB) 10, 20 mg ER tabs Given once daily or bid.1,27 2 to 8 h14,27,L Initial: 10 mg,11 or See 8#*+,#2
Wax matrix tab15 Must be swallowed whole.14 20 mg q AM for
(8#*+,#2%<8%and generics $46.85 (20 mg daily) children tolerating
from Mallinckrodt and 10 mg IR AM and
Watson are AB rated.d) noon, and adults1,5
Titration: 20 mg;5
add 2 PM dose,5 or
add 5 or 10 mg IR
tab in AM and/or at
4 PM1
%
:.6);%;%;%
#
otherwise)g,i
Extended-release (ER) methylphenidatej (continued)
B.2/)6*+f (McNeil 18, 27, 36, Given once daily in the morning 12 h16 Initial: 18 mg FDA:
Pediatrics) 54 mg ER tabs without regard to meals. Must (children six years of 54 mg
OROS (osmotic system has be swallowed whole.16 age and older and children;
hole for drug release) with $207.85 (36 mg daily) adults)1 72 mg
IR overcoat5,15,16 Titration: 18 mg1,27 adolescents
and adults
Off-label:
children up to
40 kg,
72 mg;5
adolescents
over 40 kg,
90 mg;5
adults,
108 mg5,11
:)*+7+*)%B(f (UCB) 10, 20, 30, 40, 50, Given once daily in the morning 6 to 9 h15,27 Initial: 20 mg See 8#*+,#2
Bead-filled capsule (30% IR 60 mg ER caps before breakfast. May be taken (children six years of
and 70% ER)17 whole or sprinkled over age and older and
$149.11 (20 mg daily) applesauce. If sprinkled over adults)1
applesauce, should be used Titration:
immediately and not stored for 10 to 20 mg1
future use. Capsule and/or
capsule content should not be
crushed or chewed.17
:.6);%;%;%
#
otherwise)g,i
Extended-release (ER) methylphenidatej (continued)
(+=*6+2+%(Shire) 1.1 mg/hr Worn daily for 9 hours (apply 12 h Initial: 10 mg (six FDA:
transdermal patch (10 mg/9 hr) 2 h before desired effect).18 Can (with nine-hour years of age and 30 mg18
1.6 mg/hr be worn up to 16 hours if longer wear time)19 older)18
(15 mg/9 hr) effect needed. Remove at least Titration: Next
2.2 mg/hr three hours before bedtime.19 highest patch
(20 mg/9 hr) Replace patch once daily in the strength1
3.3 mg/hr morning. Apply to hip area.
(30 mg/9 hr) Alternate application site daily.18
$193.13 (all strengths)
Amphetaminesj
@77)6+,, 5, 7.5, 10, 12.5, 15, 20, Usually given once or twice 5 to 8 hr Initial: 2.5 mg once FDA:
(mixed amphetamine salts)k 30 mg tablets daily.1,11,27 Can give second dose (duration daily (three to five 40 mg35
(Brand discontinued; six to seven hours after morning increases with years of age) or 5 mg
generics from CorePharma, $123.69 (10 mg daily) dose. Consider giving larger increasing once or twice daily Off-label:
Sandoz, and Teva are AB dose in AM. Can split max dose dose)1 (six years of age and 40 mg,27
rated.) three times daily.1 older)11 or 10 mg bid 60 mg if over
(adults)32 50 kg11
Titration:
2.5 to 5 mg once or
twice daily
(children)27 or 10 mg
bid (adults)32
:.6);%;%;%
#
otherwise)g,i
Amphetaminesj (continued)
@77)6+,,%?8e 5, 10, 15, 20, 25, Given once daily in the morning 10 h27 InitialC%%10 mg FDA:
(mixed amphetamine salts)k 30 mg ER caps without regard to meals. May be (children six to 30 mg20
(Shire) taken whole or sprinkled on 17 years of age) or
(Global Pharmaceuticals $238.25 (any strength applesauce. Sprinkled 20 mg (adults)1 Off-label:
product is an authorized daily) applesauce should not be Titration: 30 mg,
generic.h) chewed or stored for later. 5 to 10 mg1 60 mg if
Sprinkled content should not be over 50 kg11
divided.20
()D)76#2)%<9+2$0,)f Cap 5, 10, 15 mg SR caps Usually once daily in the 6 to 8 h5 Initial: 5 mg FDA:
filled with IR and SR beads morning, or bid, without regard q AM or bid 40 mg, rarely
(dextroamphetamine) $208.40 (10 mg daily) to meals.21 Do not chew beads (children six years of higher21
(Amedra Pharmaceuticals) in cap. Capsules can be opened age and older)21 or
(Generic from CorePharma and sprinkled on applesauce or 10 mg q AM Off-label:
is AB rated.) pudding (off-label).28 (adults)5 40 mg,
Titration: 5 mg1,5,31% 60 mg if
over 50 kg11
()D*6.$*+*% 5, 10 mg tablets Given two to three times daily.27 4 to 6 h27 Initial: 2.5 mg q AM FDA:
(dextroamphetamine) First dose upon awakening; (three to five years of 40 mg, rarely
(Brand discontinued; generic $31.98 (5 mg bid) additional doses at four to six age) or 5 mg q AM 60 mg30
from Teva [Barr] is AB (per drugstore.com) hour intervals.30 or bid (children six
rated.) years of age and Off-label:
older)1,30 or 5 mg 40 mg,
q AM and noon 60 mg if
(adults)31 over 50 kg11
Titration:
2.5 mg/week (three
to five years of age)
or 5 mg/week
(children six years of
age and older and
adults)5,30,31
:.6);%;%;%
#
otherwise)g,i
Amphetaminesj (continued)
&6.B)2*6+% 1 mg/mL oral solution Given two to three times daily.27 4 to 6 hours29 Initial: 2.5 mg q AM FDA:
(dextroamphetamine) First dose upon awakening; (three to five years of 40 mg,
(FSC Laboratories) $184.12 (5 mg bid) additional doses at four to six age) or 5 mg q AM rarely
hour intervals.29 or bid (children six 60 mg29
years of age and
older)29 Off-label:
Titration: 40 mg,
2.5 mg/week (three 60 mg if over
to five years of age) 50 kg11
or 5 mg/week (six
years of age and
older)29
E=4+2$) 20, 30, 40, 50, 60, Given once daily in the morning 10 to 12 h27 Initial: 30 mg FDA:
(lisdexamfetamine [prodrug 70 mg caps without regard to meals. May be (up to 14 hrs, (children six years of 70 mg22
of dextroamphetamine; taken whole or contents adults)22 age and older and
requires hydrolysis in gut for $175.57 (any strength dissolved in glass of water. If adults)1
activation; may limit abuse daily) solution prepared, it should be Titration:
potential if injected or used immediately and not 10 to 20 mg1
snorted36])% stored.22
(Shire)
%
:.6);%;%;%
#
otherwise)g,i
Nonstimulants
<*6+**)6+28% 10, 18, 25, 40, 60, 80, Given once daily or divided bid At least Initial: FDA:
(atomoxetine) 100 mg caps without regard to meals.23 10 to 12 h27 0.5 mg/kg/day children and
(Eli Lilly & Co.) (patients weighing up adolescents
$207 (40 mg daily) to 70 kg), or up to 70 kg,
Response rate is lower 40 mg/day (over 70 1.4 mg/kg;
compared to kg)1 children and
methylphenidate.1 Titration, patients up adolescents
to 70 kg: after three over 70 kg
Consider atomoxetine for days, increase to and adults,
patients with anxiety, 1.2 mg/kg/day.1 100 mg23
insomnia, or substance abuse Alternatively, after
disorders.1 four days increase to Off-label:
1 mg/kg/day, then Lesser of
Note psychiatric safety increase to 1.4 mg/kg or
concerns. 1.2 mg/kg/day after 100 mg11
four more days.11
Titration, patients
over 70 kg: after
three days, increase
to 80 mg/day1
F+94+=%% 0.1, 0.2 mg extended- Tablets should not be crushed, At least Initial: 0.1 mg at FDA:
(clonidine extended-release) release tabs chewed, or broken before 10 to 12 h27 bedtime24 0.4 mg24
(Shionogi)% swallowing. Do not substitute Titration: 0.1 mg24
$151.20 (0.1 mg bid) for other clonidine products on a
May be a good alternative mg-per-mg basis due to different Dosing is based on
for children who are pharmacokinetic profile. Doses studies in children
intolerant to stimulants (e.g., above 0.1 mg/day should be six to 17 years old.24
kids with tics, etc).1,11 May divided twice daily with an equal
be an add-on agent for or higher split dosage being
children who do not receive given at bedtime. When
enough benefit from discontinuing, taper the dose in
:.6);%;%;%
#
otherwise)g,i
stimulants alone (FDA decrements of no more than 0.1
approved for monotherapy or mg every 3 to 7 days.24
as an add-on to
stimulants).1,11,24
F+94+=%(continued)
G2*02#4% 1, 2, 3, 4 mg extended- Given once daily; avoid high-fat At least Initial: 1 mg25 FDA: 4 mg25
(guanfacine) release tabs meals. Tablets should not be 8 to 12 h26,27 Titration: 1 mg25
(Shire) crushed, chewed, or broken. Do
$194.10 (any strength not substitute for immediate- Dosing is based on
May be a good alternative daily) release guanfacine tablets on a studies in children
for children who are mg-per-mg basis due to different six to 17 years old.25
intolerant to stimulants (e.g., pharmacokinetic profiles. When
kids with tics, etc).1 May be discontinuing, taper the dose in B.2$#7)6%7.$#23%.2%+%
an add-on agent for children decrements of no more than 13HI3%5+$#$%J#*"%+%
who do not receive enough 1 mg every 3 to 7 days.25 $*+6*#23%7.$)%.K%%
benefit from stimulants alone L;LM%*.%L;LN%13HI3%
(see bullet two).1 .2/)%7+#,=;%%(.$)$%09%
*.%L;OP%13HI3%.2/)%
Not FDA approved as an 7+#,=%1+=%96.4#7)%
add-on agent; however, +77#*#.2+,%5)2)K#*;25%
guanfacine immediate-
release has been used off-
label as an add-on to
stimulants.11
There are no head-to-head

trials comparing G2*02#4 to
other ADHD medications.
However, the improvements
in mean ADHD-RS-IV
:.6);%;%;%
#
otherwise)g,i
scores were comparable to
atomoxetine at lower doses
and comparable to stimulants
at higher doses
(>0.13 mg/kg).26
G2*02#4 (continued)
a. ()$.D=2 (methamphetamine) is also FDA approved for the management of ADHD.2 However, its use has fallen out of favor with the
availability of other long-acting stimulant products. ()$.D=2%is not included in current ADHD treatment guidelines.1
b. Average wholesale price (AWP) unless otherwise indicated.
c. For stimulant products, give last dose earlier if insomnia is a problem.1
d. AB rating: actual or potential bioequivalence problems resolved with adequate #2%4#4. and/or #2%4#*6. evidence supporting bioequivalence.3
e. Releases some drug right away, then the rest later (mimics regular BID dosing).10,12,20
f. Releases an immediate dose, then gradually releases the rest.16,17,21
g. May differ from FDA-approved product information.
h. Authorized generic: generic made by the brand company but repackaged for sale under a generic name.
i. Stimulants are commonly used in preschoolers (i.e., four or five year-olds) with inadequate response to behavior therapy, but there are limited
controlled studies.11,27 Dose conservatively and titrate slowly; methylphenidate is metabolized slowly in this age group.27 In children less
than 16 kg, short-acting agents are typically used initially.11
j. Tolerance to stimulants unlikely. Plateau effect after first week is not tolerance.5 Stimulant dose based on weight, disease severity, and target
symptoms (e.g., hyperactivity may require higher doses than inattentiveness).1 Long-acting medications just as effective as shorter-acting
agents.11 Long-acting agents usually preferred for convenience and to minimize breakthrough symptoms, irritability, and headache.1 The
most common side effects of stimulants are anorexia, abdominal pain, insomnia, and headache.34 Rarely, stimulants may cause psychotic
symptoms such as hallucinations.11,34 Final adult height might be decreased by less than an inch.34
k. Mixed amphetamine salts = 75% dextroamphetamine, 25% l-amphetamine.20
L. Slow onset, variable duration.15,27
!)%'0%#,+/&(/-%#&+#&1%#/%2&#0%,&(+/#3+4#$+0%#5+/6%40(+/#7/3+4.'&(+/#
:.6);%;%;%
Dose Conversion Informationm

Previous Methylphenidate Previous Methylphenidate Recommended Recommended Methylphenidate/
Daily Dose: Daily Dose: Recommended dexmethylphenidate 9(&')(/*:9 or dextroamphetamine/mixed
Recommended#5+/,%4&' $'8&4'/' starting dose1,10 9(&')(/#"; amphetamine salts conversion
starting dose16 starting dose starting dose12
(9-hr wear-time)19,n
5 mg BID or TID: 5 mg TID or Start with half the total No specific guidance in literature.
Dosage
18 mg B.2/)6*+ every B.2/)6*+ 18 mg daily: daily dose of School-aged children and adults
conversion from
morning (+=*6+2+ 10 mg methylphenidate. For IR respond to about 1 mg/kg/day of
methylphenidate
10 mg BID or TID: 7.5 mg TID or B.2/)6*+ dexmethylphenidate, methylphenidate or
IR (BID dosing)
36 mg B.2/)6*+ every 27 mg daily: divide bid with at least 0.5 mg/kg/day of
or 8#*+,#2-<8 to
morning (+=*6+2+ 15 mg four hours between dextroamphetamine.1,11 Mixed
8#*+,#2%'@: use
15 mg BID or TID: 10 mg TID or doses. Give >./+,#2%?8 same total daily
amphetamine salts are 75%
54 mg B.2/)6*+ every B.2/)6*+ 36 mg daily: once daily in AM. If dose. Give once
dextroamphetamine, 25%
morning (+=*6+2+ 20 mg converting from IR l-amphetamine.20,35 So consider
daily. Use
20 mg BID or TID: 15 mg TID or dexmethylphenidate to clinical
switching from methylphenidate to
72 mg B.2/)6*+ every B.2/)6*+ 54 mg daily: >./+,#2%?8, use same judgment for
amphetamines at half the dose, or from
morning (+=*6+2+ 30 mg total daily dose. other
amphetamines to methylphenidate at
methylphenidate
the same dose and titrating up. Or,
regimens.
start with recommended initial dose
and titrate up.
m. May differ from product labeling. Use chart only as a guide. When converting patients from one agent to another, use clinical judgment
and monitor the patient closely for clinical and adverse effects.
n. FDA-approved labeling recommends patients converting from other methylphenidate formulations start with 10 mg due to differences in
bioavailability among products.18
Q$)6$%.K%*"#$%&'%()*+#,-(./01)2*%+6)%/+0*#.2)7%*.%0$)%*")#6%.J2%96.K)$$#.2+,%R0731)2*%+27%/.2$0,*%+2=%.*")6%2)/)$$+6=%.6%+996.96#+*)%$.06/)$%96#.6%*.%1+I#23%
/,#2#/+,%R0731)2*$%5+$)7%.2%*")%/.2*)2*%.K%*"#$%7./01)2*;%%S06%)7#*.6$%"+4)%6)$)+6/")7%*")%#2K.61+*#.2%J#*"%#290*%K6.1%)D9)6*$T%3.4)621)2*%+3)2/#)$T%+27%2+*#.2+,%
.63+2#U+*#.2$;%%G2K.61+*#.2%+27%#2*)62)*%,#2I$%#2%*"#$%+6*#/,)%J)6)%/066)2*%+$%.K%*")%7+*)%.K%905,#/+*#.2;
:.6);%;%;%
!4+<%,&# "%'=%4# (/# >4%>'4'&(+/# +3# &1(0# !"# $%&'()* 15. Elia J. Attention deficit/hyperactivity disorder:
$+,-.%/&?##:),+2#)%B099T%&"+61;(;T%VB&<%# pharmacotherapy. Psychiatry (Edgmont) 2005;2:27-
35.
16. Product information for Concerta. McNeil Pediatrics.
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:.6);%;%;%
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#
#
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Comparison of Drugs for ADHD

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34. Subcommittee on Attention-Deficit/Hyperactivity 36. PL Detail-Document, New Drug: Vyvanse

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