- Email: [email protected]
Medications for ADHD
CHAPTER 15
Medications for ADHD CURRENT FDA-APPROVED MEDICATIONS FOR ADHD
Medications for ADHD: Amphetamines and Nonstimulants (Brand Names are Listed. Some Have Generic Forms.) Harlan R. Gephart, MD Medications
Available Forms (mg)
Initial Dose (mg)
Peak Dose (h)
Duration (h)
Comments
AMPHETAMINES (BRAND NAMES) Short Acting Adderall
5, 7.5, 10, 12.5, 15, 20, 30
5
3
4e6
Highly abused
Dextrostat (dextroamphetamine)
5, 10
5
3
4e6
Highly abused
ProCenta
5 mg/5 mL
5
2e4
4e6
May cause Raynaud phenomenon
20, 30, 40, 50, 60, 70
20
3.5e4.5
8e12
Capsule can be opened and sprinkled or dissolved in liquid. CANNOT BE ABUSED BY SNORTING.
Long Acting Vyvanse
Adderall XR
5, 10, 15, 20, 30
5
3e5
8e12
Highly abused
Dexedrine spansule
5, 10, 15
5
3e4
6e10
Highly abused
a
3.1, 6.3, 9.4, 12.5, 15.7, 18.8
3.1 or 6.3
5
10e11
ALLOW PILL TO FIRST DISSOLVE ON TONGUE
2.5 mg/mL
2.5e5.0
1
13
Maximum dose, 20.0 mg
Adzenys XR-ODT
a
Dyanavel XR (suspension) NONSTIMULANTS
a-Agonists/Long Acting Intuniv (guanfacine)
1, 2, 3, 4
1
8e12
Maximum dose for ages 6e12 years, 4 mg ages 13e17 years, 7 mg
Kapvay (clonidine)
0.1
0.1 (greater doses should be split bid)
8e12
If discontinued need to taper 0.1 mg every 3e7 days. Maximum dose, 0.4 mg Continued
105
106
ADHD Complex
Medications for ADHD: Amphetamines and Nonstimulants (Brand Names are Listed. Some Have Generic Forms.) Harlan R. Gephart, MDdcont'd Available Forms (mg)
Medications
Initial Dose (mg)
Peak Dose (h)
Duration (h)
Comments
0.5 mg/kg per day. In 2 weeks, 1.2 mg/kg per day. Do not exceed 1.4 mg/kg per day.
Target 1.2 mg/ kg per day Do not exceed 1.4 mg/kg per day
18e24
See some effect at 1e2 weeks, peak at 2e4 weeks BOX WARNING!
Antidepressant Strattera (atomoxetine)
a
10, 18, 25, 40, 60, 80, 100
New.
Medications for ADHD: Methylphenidates (Brand Names are Listed. Some Have Generic Forms.) Harlan R. Gephart, MD Available Forms (mg)
Initial Dose (mg)
Peak Dose (h)
Duration (h)
Ritalin
5, 10, 20
5.0
2e3
4
Focalin
2.5, 5, 10
2.5
2e3
4e5
Methylin
5, 10, 20
5.0
2e3
4e6
Methylin chewable
2.5, 5, 10
2.5
2e3
4e6
Methylin solution
5 mg/5 mL and 10 mg/5 mL
5
2e4
4
Brand Name
Comments
SHORT ACTING Twice as strong as other methylphenidates
LONG ACTING (8e12 H) Concerta
18, 27, 36, 54
18
6e8
8e12
Focalin XR
5, 10, 15, 20
5
3e4
8e12
Ritalin LA
10, 20, 30, 40
10
3e5
4e8
Metadate CD
10, 20, 30, 40, 50, 60
10
3e5
4e8
Ritalin SR
20
20
3e4
6e8
Methylin ER
10, 20
10
3e5
4e8
a
Quillivant XR (liquid)
25 mg/5 mL
1e2 mL
45 min
8e12
a
QuilliChew ER (chewable)
20, 30, 40
20
45 min
8
a
10, 15, 20, 30, 40, 50, 60
10
Effects seen at 1 h
12
Capsules may be opened and sprinkled
10, 15, 20, 30
10
2
12 h plus 3 h after patch removed
May cause skin rash
Aptensio XR
Daytrana patch a
New.
Twice as strong as other methylphenidates
Old medication; unreliable
CHAPTER 15 Medications for ADHD Addendum: Four pharmaceutical companies have recently received FDA approval to market generic atomoxetine (Strattera). They are Apotex, Teva Pharmaceutical Industries, Aurobindo Pharma, and Glenmark Pharma.
RISK OF MEDICATION ABUSE/DIVERSION 1) Self-medication: About 5% of college students (various sources) illicitly used stimulants in the past year (most commonly, Adderall). • To study better for tests • Less likely to get “high” 2) Diversion (Wilens, JAACAP 2006) • About 22% of adolescents with ADHD misused their prescribed medications • About 11% sold their medications • One-third of adolescents have “tried medications” Risks of giving or selling one’s medications should be discussed prior to initiation of treatment. For example, perhaps another adolescent has an undiagnosed heart condition, for whom stimulant medications might be life-threatening. Stress that some medicines need to be tapered, e.g., selective serotonin reuptake inhibitors.
ISSUES TO BE ADDRESSED PRIOR TO ADMINISTRATION OF MEDICATIONS 1) Self-image: Adolescent is being treated for a medical condition, not being “drugged” by the clinician. 2) Friends may say, “I don’t like you on medications” (because of a decrease in inappropriate behaviors, such as blurting out in class). 3) Side effects: Potential, acceptable/not acceptable. 4) “Loss of creativity” and “zombie feeling”: Almost always due to too large a dose. 5) Risk to others if medications diverted, for example, potential unknown cardiac risk. 6) Necessity for compliance, not sporadic usage or dosage variation. 7) Risks of inappropriate usage, for example, snorting vs. ingesting. 8) Risks if other substances are used (e.g., pot, alcohol) when taking medications. 9) Need for frequent monitoring (appointments, school reports, etc.). 10) The good news! Most children/adolescents (w80%e90% informal data from our large clinic) who take ADHD medications will not need them as
107
adults, hopefully due to having an interesting and motivating job and the burden of school being lifted after high school or college (many do not find medications necessary after 2e3 years of college). ADHD symptoms actually do lessen with age for many patients, and the adolescent/adult also learns coping skills that also minimize symptoms. PEARL: Remember, however, that even though the ADHD symptoms are lessened, or maybe not recognizable enough for an ADHD diagnosis, the adolescent/adult might well be left with a comorbid condition, such as anxiety or depression, and need help with that.
RECENT MEDICATIONS APPROVED BY THE FDA FOR ADHD TREATMENT 1) Adzenys XR-ODT (Neos Therapeutics) An amphetamine For ages 6 years and over Has both immediate and long-acting effects Orally disintegrates and can be taken without water 2) Quillivant XR (Pfizer Ltd.) A long-acting liquid methylphenidate For ages 6 years and over 3) QuilliChew ER (Pfizer Ltd.) A long-acting chewable methylphenidate For ages 6 years and over 4) Dyanavel XR (Tris Pharma) A long-acting amphetamine suspension For ages 6 years and over 5) Mydayis (Shire Plc.) Long-acting mixed amphetamine salts For ages 13 years and over, including adults Onset, 2e4 h; lasts up to 16 h Available from late fall 2017 6) Cotempla XR-ODT (Neos Therapeutics) A methylphenidate extended-release oral medicine; disintegrating For ages 6e17 years Available doses: 17.3, 25.9, 34.6, and 51.8 mg Onset, 1 h; duration, 12 h Available from fall 2017 7) New generic Concerta (Helio.com) Doses: 18, 27, 36, and 54 mg PEARL: One must always be cautious when prescribing oral liquid medications, as there is a body of evidence that the doses given to the child vary widely (“not every teaspoon is 5 mL!”), unless one provides a measured spoon or dropper. PEARL: August 2016 Journal of the American Academy of Child and Adolescent Psychiatry.
108
ADHD Complex
Three studies suggest combinations of medications, e.g., stimulants and a-agonists (e.g., Intuniv, Kapvay), may give greater clinical improvement than when used alone. We noted this result in our clinic years ago, with both a-agonists and atomoxetine (see the section “What to do when your favorite ADHD medication doesn’t work in the ADHD treatment chapter 4”). This research should help us get two medications simultaneously covered by healthcare insurers, which has been somewhat of a struggle to date. However, our goal should always be to maximize a response to one medication and avoid multiple medications if at all possible. PEARL: Dr. William Brinkman presented data from a National Institute of Mental Health study (394 kids) at the Pediatric Academic Societies in May 2016, regarding teenagers who stop their ADHD medication on their own. He noted that • almost all teens stop medications at some point, • only w28% restart them, • the reasons given were • “Felt I could do OK without it.” • “Wanted to see if I could do without it.” • “Tired of taking it.” • “Side effects.” • “Parents stopped it.” We need to be aware of these concerns, perhaps even participate in (and supervise) a controlled trial on and off medications.
Most teenagers with ADHD do not do well if they stop their medications, in our experience and based on at least some limited research data. The experience from our large clinic was that most adolescents who are on ADHD medications need to continue them (perhaps in decreasing doses) through high school and into college for 1e2 years, before considering a trial off of them. PEARL: It was mentioned earlier that generic medications are sometimes not as effective as the brand name medications, and careful observation is needed when going from brand name to generic medications. On October 18, 2016, FDA removed two generic medications (generic forms of Concerta, a long-acting methylphenidate) from its approved list, one manufactured by Mallinckrodt and the other by UCB/Kremers Urban, formerly Kudco. The reasons for removal are a) failed to demonstrate bioequivalence to the brand name medication, b) may not have the same therapeutic benefits as the brand name medication. In August 2018 the FDA approved a new ADHD methylphenidate medication (Brand name Jornay PM), manufactured by Ironshore Pharmaceuticals, for evening usage, at an initial dose of 20 mg given between 6:30 PM and 9:00 PM to children 6 years and older, to enable control of ADHD in the early AM the following day. It should be on the market early 2019.
Medications for ADHD CURRENT FDA-APPROVED MEDICATIONS FOR ADHD
Medications for ADHD: Amphetamines and Nonstimulants (Brand Names are Listed. Some Have Generic Forms.) Harlan R. Gephart, MD Medications
Available Forms (mg)
Initial Dose (mg)
Peak Dose (h)
Duration (h)
Comments
AMPHETAMINES (BRAND NAMES) Short Acting Adderall
5, 7.5, 10, 12.5, 15, 20, 30
5
3
4e6
Highly abused
Dextrostat (dextroamphetamine)
5, 10
5
3
4e6
Highly abused
ProCenta
5 mg/5 mL
5
2e4
4e6
May cause Raynaud phenomenon
20, 30, 40, 50, 60, 70
20
3.5e4.5
8e12
Capsule can be opened and sprinkled or dissolved in liquid. CANNOT BE ABUSED BY SNORTING.
Long Acting Vyvanse
Adderall XR
5, 10, 15, 20, 30
5
3e5
8e12
Highly abused
Dexedrine spansule
5, 10, 15
5
3e4
6e10
Highly abused
a
3.1, 6.3, 9.4, 12.5, 15.7, 18.8
3.1 or 6.3
5
10e11
ALLOW PILL TO FIRST DISSOLVE ON TONGUE
2.5 mg/mL
2.5e5.0
1
13
Maximum dose, 20.0 mg
Adzenys XR-ODT
a
Dyanavel XR (suspension) NONSTIMULANTS
a-Agonists/Long Acting Intuniv (guanfacine)
1, 2, 3, 4
1
8e12
Maximum dose for ages 6e12 years, 4 mg ages 13e17 years, 7 mg
Kapvay (clonidine)
0.1
0.1 (greater doses should be split bid)
8e12
If discontinued need to taper 0.1 mg every 3e7 days. Maximum dose, 0.4 mg Continued
105
106
ADHD Complex
Medications for ADHD: Amphetamines and Nonstimulants (Brand Names are Listed. Some Have Generic Forms.) Harlan R. Gephart, MDdcont'd Available Forms (mg)
Medications
Initial Dose (mg)
Peak Dose (h)
Duration (h)
Comments
0.5 mg/kg per day. In 2 weeks, 1.2 mg/kg per day. Do not exceed 1.4 mg/kg per day.
Target 1.2 mg/ kg per day Do not exceed 1.4 mg/kg per day
18e24
See some effect at 1e2 weeks, peak at 2e4 weeks BOX WARNING!
Antidepressant Strattera (atomoxetine)
a
10, 18, 25, 40, 60, 80, 100
New.
Medications for ADHD: Methylphenidates (Brand Names are Listed. Some Have Generic Forms.) Harlan R. Gephart, MD Available Forms (mg)
Initial Dose (mg)
Peak Dose (h)
Duration (h)
Ritalin
5, 10, 20
5.0
2e3
4
Focalin
2.5, 5, 10
2.5
2e3
4e5
Methylin
5, 10, 20
5.0
2e3
4e6
Methylin chewable
2.5, 5, 10
2.5
2e3
4e6
Methylin solution
5 mg/5 mL and 10 mg/5 mL
5
2e4
4
Brand Name
Comments
SHORT ACTING Twice as strong as other methylphenidates
LONG ACTING (8e12 H) Concerta
18, 27, 36, 54
18
6e8
8e12
Focalin XR
5, 10, 15, 20
5
3e4
8e12
Ritalin LA
10, 20, 30, 40
10
3e5
4e8
Metadate CD
10, 20, 30, 40, 50, 60
10
3e5
4e8
Ritalin SR
20
20
3e4
6e8
Methylin ER
10, 20
10
3e5
4e8
a
Quillivant XR (liquid)
25 mg/5 mL
1e2 mL
45 min
8e12
a
QuilliChew ER (chewable)
20, 30, 40
20
45 min
8
a
10, 15, 20, 30, 40, 50, 60
10
Effects seen at 1 h
12
Capsules may be opened and sprinkled
10, 15, 20, 30
10
2
12 h plus 3 h after patch removed
May cause skin rash
Aptensio XR
Daytrana patch a
New.
Twice as strong as other methylphenidates
Old medication; unreliable
CHAPTER 15 Medications for ADHD Addendum: Four pharmaceutical companies have recently received FDA approval to market generic atomoxetine (Strattera). They are Apotex, Teva Pharmaceutical Industries, Aurobindo Pharma, and Glenmark Pharma.
RISK OF MEDICATION ABUSE/DIVERSION 1) Self-medication: About 5% of college students (various sources) illicitly used stimulants in the past year (most commonly, Adderall). • To study better for tests • Less likely to get “high” 2) Diversion (Wilens, JAACAP 2006) • About 22% of adolescents with ADHD misused their prescribed medications • About 11% sold their medications • One-third of adolescents have “tried medications” Risks of giving or selling one’s medications should be discussed prior to initiation of treatment. For example, perhaps another adolescent has an undiagnosed heart condition, for whom stimulant medications might be life-threatening. Stress that some medicines need to be tapered, e.g., selective serotonin reuptake inhibitors.
ISSUES TO BE ADDRESSED PRIOR TO ADMINISTRATION OF MEDICATIONS 1) Self-image: Adolescent is being treated for a medical condition, not being “drugged” by the clinician. 2) Friends may say, “I don’t like you on medications” (because of a decrease in inappropriate behaviors, such as blurting out in class). 3) Side effects: Potential, acceptable/not acceptable. 4) “Loss of creativity” and “zombie feeling”: Almost always due to too large a dose. 5) Risk to others if medications diverted, for example, potential unknown cardiac risk. 6) Necessity for compliance, not sporadic usage or dosage variation. 7) Risks of inappropriate usage, for example, snorting vs. ingesting. 8) Risks if other substances are used (e.g., pot, alcohol) when taking medications. 9) Need for frequent monitoring (appointments, school reports, etc.). 10) The good news! Most children/adolescents (w80%e90% informal data from our large clinic) who take ADHD medications will not need them as
107
adults, hopefully due to having an interesting and motivating job and the burden of school being lifted after high school or college (many do not find medications necessary after 2e3 years of college). ADHD symptoms actually do lessen with age for many patients, and the adolescent/adult also learns coping skills that also minimize symptoms. PEARL: Remember, however, that even though the ADHD symptoms are lessened, or maybe not recognizable enough for an ADHD diagnosis, the adolescent/adult might well be left with a comorbid condition, such as anxiety or depression, and need help with that.
RECENT MEDICATIONS APPROVED BY THE FDA FOR ADHD TREATMENT 1) Adzenys XR-ODT (Neos Therapeutics) An amphetamine For ages 6 years and over Has both immediate and long-acting effects Orally disintegrates and can be taken without water 2) Quillivant XR (Pfizer Ltd.) A long-acting liquid methylphenidate For ages 6 years and over 3) QuilliChew ER (Pfizer Ltd.) A long-acting chewable methylphenidate For ages 6 years and over 4) Dyanavel XR (Tris Pharma) A long-acting amphetamine suspension For ages 6 years and over 5) Mydayis (Shire Plc.) Long-acting mixed amphetamine salts For ages 13 years and over, including adults Onset, 2e4 h; lasts up to 16 h Available from late fall 2017 6) Cotempla XR-ODT (Neos Therapeutics) A methylphenidate extended-release oral medicine; disintegrating For ages 6e17 years Available doses: 17.3, 25.9, 34.6, and 51.8 mg Onset, 1 h; duration, 12 h Available from fall 2017 7) New generic Concerta (Helio.com) Doses: 18, 27, 36, and 54 mg PEARL: One must always be cautious when prescribing oral liquid medications, as there is a body of evidence that the doses given to the child vary widely (“not every teaspoon is 5 mL!”), unless one provides a measured spoon or dropper. PEARL: August 2016 Journal of the American Academy of Child and Adolescent Psychiatry.
108
ADHD Complex
Three studies suggest combinations of medications, e.g., stimulants and a-agonists (e.g., Intuniv, Kapvay), may give greater clinical improvement than when used alone. We noted this result in our clinic years ago, with both a-agonists and atomoxetine (see the section “What to do when your favorite ADHD medication doesn’t work in the ADHD treatment chapter 4”). This research should help us get two medications simultaneously covered by healthcare insurers, which has been somewhat of a struggle to date. However, our goal should always be to maximize a response to one medication and avoid multiple medications if at all possible. PEARL: Dr. William Brinkman presented data from a National Institute of Mental Health study (394 kids) at the Pediatric Academic Societies in May 2016, regarding teenagers who stop their ADHD medication on their own. He noted that • almost all teens stop medications at some point, • only w28% restart them, • the reasons given were • “Felt I could do OK without it.” • “Wanted to see if I could do without it.” • “Tired of taking it.” • “Side effects.” • “Parents stopped it.” We need to be aware of these concerns, perhaps even participate in (and supervise) a controlled trial on and off medications.
Most teenagers with ADHD do not do well if they stop their medications, in our experience and based on at least some limited research data. The experience from our large clinic was that most adolescents who are on ADHD medications need to continue them (perhaps in decreasing doses) through high school and into college for 1e2 years, before considering a trial off of them. PEARL: It was mentioned earlier that generic medications are sometimes not as effective as the brand name medications, and careful observation is needed when going from brand name to generic medications. On October 18, 2016, FDA removed two generic medications (generic forms of Concerta, a long-acting methylphenidate) from its approved list, one manufactured by Mallinckrodt and the other by UCB/Kremers Urban, formerly Kudco. The reasons for removal are a) failed to demonstrate bioequivalence to the brand name medication, b) may not have the same therapeutic benefits as the brand name medication. In August 2018 the FDA approved a new ADHD methylphenidate medication (Brand name Jornay PM), manufactured by Ironshore Pharmaceuticals, for evening usage, at an initial dose of 20 mg given between 6:30 PM and 9:00 PM to children 6 years and older, to enable control of ADHD in the early AM the following day. It should be on the market early 2019.