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DRUGS FOR ADHD: ADOLESCENTS TO ADULTS
DISCLOSURE
Natasha Rodney-Cail, Pharmacist, Drug Evaluation Unit
Has no conflicts of interest
Dr. James Chandler, MD, FRCPC
Has no conflicts of interest
Age 18
Diagnosed with ADHD, combined type, at 8 years of age
Taking Biphentin 50 mg OD, last 6 years
Just started university and would like to stop his ADHD medication
STEVEN
25 years old
ADHD, combined type, diagnosed at age 16
Finished university, started work 2 years ago
ADHD has not been re-evaluated as an adult
Currently taking Foquest 70 mg OD
SARAH
Ontario Drug Policy Research Network – Treatments for Attention Deficit Hyperactivity Disorder in Adults Final Pharmacoepidemiology Report. Accessed September 14, 2018
http://odprn.ca/wp-content/uploads/2015/12/ADHD-Pepi-Report-Final_Dec-22-2015.pdf
3 CORE SYMPTOMS
Hyperactivity Inattention Impulsivity
ADHD
Combined
Inattention with hyperactivity
Predominantly Inattentive
Inattention without hyperactivity
Predominantly Hyperactive-Impulsive
Hyperactivity without inattention
Adults with ADHD are rarely hyperactive
Inattention remains
Hyperactivity may become restlessness
https://www.caddra.ca/practice-guidelines/
Before
the age
of 12
https://www.caddra.ca/practice-guidelines/
DSM-5 Criteria
Prevalence Magnitude
ADHD IN ADULTS
CLINICAL QUESTIONS
When is the best time to reassess the transition from adolescents to adults?
Do all adult patients with ADHD require medication?
When diagnosed as children and progress into adulthood
When diagnosed as adults
Adult onset?
How often should medication therapy be reassessed?
Things to consider when evaluating medication therapy
DRUGS USED TO TREAT ADHD
1st line
Long acting stimulants
2nd line
Short or intermediate
acting stimulants
and
non-stimulant
https://www.caddra.ca/practice-guidelines
WHAT TO CONSIDER…..
HEALTH CANADA APPROVED FORMULATIONS
Class/Drug Formulation Typical Dose
Long Acting Stimulants
Methylphenidate
Mixed amphetamine salts
Lisdexamphetamine
MPH-OROS
MPH-ER
MPH-CR
MAS-XR
LIS-DEX
18-72 mg/day
10-80 mg/day
25-100 mg/day
10-30 mg/day
20-70mg/day
Intermediate Acting Stimulants
Methylphendiate
Dextroamphetamine
MPH-SR
DEX-SR
20-60 mg/day
10-60 mg/day
Short Acting Stimulants
Methylphenidate
Dextroamphetamine
MPH-IR
DEX-IR
10-60 mg/day
10-60 mg/day
Non-Stimulants
Atomoxetine
Guanfacine
ATX
GUAN-ER
40-100 mg/day
1-7 mg/day
STEPPED APPROACH TO PRESCRIBING
https://www.caddra.ca/practice-guidelines
OUTCOMES IN CLINICAL TRIALS
• Symptoms
• Quality of life
• Executive function
• Functional outcomes
EVIDENCE IN ADOLESCENTS?
Stimulants (methylphenidate, mixed amphetamine salts XR, lisdexamphetamine)
• Studied in a small number of short-term trials (≤ 4 weeks)
• Generally superior to placebo in improving core ADHD symptoms, but associated with reports of appetite and sleep disturbances.
• QOL not different among groups
Non-stimulant (atomoxetine)
• Pooled with children
• Improvement on ADHD rating scale maintained to 24 months in open label extension.
https://www.ohsu.edu/xd/research/centers-institutes/evidence-based-practice-center/drug-
effectiveness-review-project/upload/ADHD_final-report_update-4_December-2011.pdf
RESPONSE RATE FOR IMPROVEMENT OF SYMPTOMS
For HC approved stimulants and non-stimulants for adults
Number needed to treat = 2 to 6
DERP 2011
https://www.ohsu.edu/xd/research/centers-institutes/evidence-based-practice-center/drug-
effectiveness-review-project/upload/ADHD_final-report_update-4_December-2011.pdf
What is the evidence for ADHD drug
treatments in Adults?
MPH OROS
MPH IR
DEX- IR
ATX
= significant compared to placebo
= not significant compared to placebo
PATIENT REPORTED CLINICAL RESPONSE, N=4,575
Placebo
http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/
= significant compared to placebo
= not significant compared to placebo
OBSERVER REPORTED CLINICAL RESPONSE, N=3,548
Placebo
MAS-XR
ATX
DEX-IRMPH-IR
MPH OROS
http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/
QUALITY OF LIFE, N=3,394
MAS-XR
ATX
LIS-DEX
MPH OROS Placebo
= significant compared to placebo
= not significant compared to placebo
http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/
EXECUTIVE FUNCTION, N=2,140
MAS-XR
ATX
LIS-DEX
MPH OROS
= not significant compared to placebo
Placebo
http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/
FUNCTIONAL IMPROVEMENTS
Trial data lacking for functional improvements Social
Academic
Occupational productivity
DERP and ODPRN.
http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/
https://www.ohsu.edu/xd/research/centers-institutes/evidence-based-practice-center/drug-
effectiveness-review-project/upload/ADHD_final-report_update-4_December-2011.pdf
DIFFERENCES BETWEEN THERAPIES
No differences for: Patient reported clinical response
QOL
Executive function
High dose mixed amphetamine salts better than other
therapies at improving observer reported clinical response
http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/
https://www.ohsu.edu/xd/research/centers-institutes/evidence-based-practice-center/drug-
effectiveness-review-project/upload/ADHD_final-report_update-4_December-2011.pdf
LONG TERM EFFICACY IN ADULTS
RCTs (maximum duration ~ 6 months)
Long acting methyphenidate or atomoxetine (5 trials)
Improvement in symptom scales
> with active treatment vs. placebo
Open label extension trials
Sustained symptomatic improvement
Long acting methylphenidate up to 2 years
Mixed amphetamine salts and lisdexamphetamine up to 1 year
Atomoxetine up to 4 years
https://www.ohsu.edu/xd/research/centers-institutes/evidence-based-practice-center/drug-
effectiveness-review-project/upload/ADHD_final-report_update-4_December-2011.pdf
Fredriksen et al. European Neruospsychopharmacology 2013; 23: 508-527
Is there evidence for ADHD medications
during the transition from adolescents
to adults?.......
Cochrane Review:
Immediate release methylphenidate for ADHD in adults
Cochrane Review:
Amphetamines for ADHD in adults
• Improved severity of symptoms, as assessed by clinicians or patients, in the short term, did not improve retention to treatment.
• Associated with higher attrition due to AE.
• The short duration of studies and restrictive inclusion criteria limits the external validity of these findings.
• None of the included studies had an overall low risk of bias.
• Overall, the evidence generated by this review is of low or very low quality.
• https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007813.pub3/full?highlightAbstract=adhd
QUALITY OF THE EVIDENCE
SAFETY
Evidence (up to 6 months)
Treatments are not associated with increased odds of serious AE
HC approved medications associated with higher odds of withdrawal due to AE Odds of being a responder is similar to odds of
withdrawal due to AE
Evidence (up to 4 years)
Long term stimulant treatment associated with increases in BP and HR
There is little data on the long term safety of stimulants in adults ≥50 years of age
EVIDENCE FOR ADVERSE EFFECTS IN ADULTS
http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/
No differences between treatments for odds
of withdrawal due to AE.
EVIDENCE ON THE RISK OF ABUSE, MISUSE OR DIVERSION
Evidence suggests that misuse/abuse and diversion
occurs; it is most prevalent in college age
students
It is estimated that the number of
potentially inappropriate
prescriptions in Canada is low
http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/
PROSPECTIVE COURSE OF ADHD ADOLESCENTS TO ADULTS
A significant number of people choose to stop medication
for a variety of reasons…….
Side effects
Desire for independence
A lack of continuity of healthcare
Social stigma
“Remission”
Lack of continued effect?
When should patients be evaluate/re-evaluated for continued medication?
Age 19
Diagnosed with ADHD, combined type, at 8 years of age
Taking Biphentin 50 mg OD, last 6 years
Just started university and would like to stop his ADHD medication
STEVEN
25 years old
ADHD, combined type, diagnosed at age 16 years
Finished university and started work 2 years ago
ADHD has not been re-evaluated as an adult
Currently taking Foquest 70 mg OD for past year
SARAH
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