DRUGS FOR ADHD: ADOLESCENTS TO ADULTS

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

STEVEN 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

SARAH 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

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

Predominantly Inattentive Combined Inattention with hyperactivity Inattention without hyperactivity Predominantly Hyperactive-Impulsive Hyperactivity without inattention ADHD

Inattention remains Adults with ADHD are rarely hyperactive Hyperactivity may become restlessness

https://www.caddra.ca/practice-guidelines/

DSM-5 Criteria Before the age of 12 https://www.caddra.ca/practice-guidelines/

ADHD IN ADULTS Prevalence Magnitude

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 1 st line Long acting stimulants 2 nd 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 Intermediate Acting Stimulants Methylphendiate Dextroamphetamine Short Acting Stimulants Methylphenidate Dextroamphetamine Non-Stimulants Atomoxetine Guanfacine MPH-OROS MPH-ER MPH-CR MAS-XR LIS-DEX MPH-SR DEX-SR MPH-IR DEX-IR ATX GUAN-ER 18-72 mg/day 10-80 mg/day 25-100 mg/day 10-30 mg/day 20-70mg/day 20-60 mg/day 10-60 mg/day 10-60 mg/day 10-60 mg/day 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/drugeffectiveness-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 https://www.ohsu.edu/xd/research/centers-institutes/evidence-based-practice-center/drugeffectiveness-review-project/upload/adhd_final-report_update-4_december-2011.pdf DERP 2011

What is the evidence for ADHD drug treatments in Adults?

MPH OROS ATX Placebo MPH IR DEX- IR PATIENT REPORTED CLINICAL RESPONSE, N=4,575 = significant compared to placebo = not significant compared to placebo http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/

MAS-XR MPH OROS Placebo ATX MPH-IR DEX-IR OBSERVER REPORTED CLINICAL RESPONSE, N=3,548 = significant compared to placebo = not significant compared to placebo http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/

MAS-XR MPH OROS Placebo ATX LIS-DEX QUALITY OF LIFE, N=3,394 = significant compared to placebo = not significant compared to placebo http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/

MAS-XR MPH OROS Placebo ATX LIS-DEX EXECUTIVE FUNCTION, N=2,140 = not significant compared to 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. https://www.ohsu.edu/xd/research/centers-institutes/evidence-based-practice-center/drugeffectiveness-review-project/upload/adhd_final-report_update-4_december-2011.pdf http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/

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 https://www.ohsu.edu/xd/research/centers-institutes/evidence-based-practice-center/drugeffectiveness-review-project/upload/adhd_final-report_update-4_december-2011.pdf http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/

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/drugeffectiveness-review-project/upload/adhd_final-report_update-4_december-2011.pdf

Is there evidence for ADHD medications during the transition from adolescents to adults?...

QUALITY OF THE EVIDENCE 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

SAFETY

EVIDENCE FOR ADVERSE EFFECTS IN ADULTS 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 No differences between treatments for odds of withdrawal due to AE. http://odprn.ca/research/core-themes/drug-class-reviews/attention-deficit-hyperactivity-disorder/

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?

STEVEN 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

SARAH 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