drugs for adhd: adolescents to adults · drugs for adhd: adolescents to adults. disclosure natasha...

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

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



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/



OBSERVER REPORTED CLINICAL RESPONSE, N=3,548

Placebo

MAS-XR

ATX

DEX-IRMPH-IR

MPH OROS


QUALITY OF LIFE, N=3,394

MAS-XR

ATX

LIS-DEX

MPH OROS Placebo




EXECUTIVE FUNCTION, N=2,140

MAS-XR

ATX

LIS-DEX

MPH OROS


Placebo


FUNCTIONAL IMPROVEMENTS

Trial data lacking for functional improvements Social

Academic

Occupational productivity

DERP and ODPRN.




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




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



Fredriksen et al. European Neruospsychopharmacology 2013; 23: 508-527

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

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

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007813.pub3/full?highlightAbstract=adhd

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


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


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

drugs for adhd: adolescents to adults · drugs for adhd: adolescents to adults. disclosure natasha...

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