Drug for ADHD

1. Dr. Subodh Sharma
Resident, MD Psychiatry
Department of Psychiatry
NMCTH, Birgunj , Nepal

2. Selective Norepinephrine Reuptake Inhibitor
Approved in 2002 for treatment of ADHD
Developed by Eli Lilly Pharmaceuticals (Strattera)
Off label use: Uni/Bipolar Depression
Weak antidepressant

3. Norepinephrine Reuptake Inhibition,
Dopamine facilitation in PFC
Increases Cortical Acetylcholine level

4.  Duration of action: Up to 24 hours
 Absorption: Rapid
 Distribution: Vd: IV: 0.85 L/kg
 Protein binding: 98%, primarily albumin
 Metabolism: Hepatic, via CYP2D6 and CYP2C19
 Half-life elimination: Atomoxetine: 5 hours (up to 24 hours in poor
metabolizers)
 Time to peak, plasma: 1-2 hours; delayed high-fat meal
 Excretion: Urine (80%) <3% is excreted unchanged); feces (17%)

5.  Comparative efficacy and safety of methylphenidate and atomoxetine for attention-
deficit hyperactivity disorder in children and adolescents: Meta-analysis based on
head-to-head trials Qiang Liu Et. Al. 2017
 Included 11 studies from all over the world from 2002-2013
 Concluded that Methylphenidate should be the first line of treatment in children
and adolescent.
 “Compared to ATX, MPH showed a higher response rate (RR = 1.14, 95% CI [1.
09, 1.20]), decreased inattention (SMD = −0.13, 95% CI [−0.25, −0.01]) and
lower risk of adverse events (drowsiness: RR = 0.17, 95% CI [0.11, 0.26; nausea:
RR = 0.49; 95% CI [0.29, 0.85; vomiting: RR = 0.41, 95% CI [0.27, 0.63]).”

7.  Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine,
bupropion and methylphenidate in treatment of attention deficit hyperactivity
disorder in children and adolescents: A meta-analysis with focus on bupropion;
Matej Stuhec et. Al. 2015
 Efficacy in reducing ADHD symptoms compared to placebo was small for
bupropion, while modest efficacy was shown for atomoxetine and
methylphenidate and high efficacy was observed for lisdexamfetamine.
 Compared to placebo treatment discontinuation was statistically significantly
lower for methylphenidate, while it was not significantly different for
atomoxetine, lisdexamfetamine, and bupropion

8.  Comparative efficacy and tolerability of medications for attention-deficit
hyperactivity disorder in children, adolescents, and adults: a systematic review
and network meta-analysis; Samuele Cortese et. al. 2018; The Lancet
 Clinician rating; all drugs i.e. Methylphenidate, Amphetamine, Modafinil and
Atomoxetine were superior than placebo.
 Teacher rating; only Methylphenidate and Modafinil were efficacious than
placebo
 Adult clinician rating: amphetamines, methylphenidate, bupropion, and
atomoxetine, but not modafinil, were better than placebo.

9.  With respect to tolerability, amphetamines were inferior to placebo in both
children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36–3·89) and adults
(3·26, 1·54–6·92)
 Atomoxetine (2·33, 1·28–4·25), Methylphenidate (2·39, 1·40–4·08), and
Modafinil (4·01, 1·42–11·33) were less well tolerated than placebo in adults
only.
 In head-to-head comparisons, only differences in efficacy (clinicians’ ratings)
were found, favoring amphetamines over modafinil, atomoxetine, and
methylphenidate in both children and adolescents (SMDs –0·46 to –0·24) and
adults (–0·94 to –0·29).

10.  Similar efficacy to IR Methylphenidate.
 Mild to Moderate side effects.
 Treatment algorithms involving the initial use of atomoxetine appear cost
effective versus algorithms involving initial methylphenidate (immediate- or
extended-release), dexamphetamine, tricyclic antidepressants.
 Data suggest that atomoxetine is unlikely to have any abuse potential.
 Atomoxetine appeared less likely than methylphenidate to exacerbate
disordered sleep in pediatric patients with ADHD.
 Atomoxetine; A Review of its Use in Attention-Deficit Hyperactivity Disorder in Children
and Adolescents; Karly P. Garnock-Jones et al, 2009

11.  Atomoxetine may be preferred in patients with :
 Other comorbid psychiatric disorders,
 Those who cannot tolerate stimulants,
 those with a substance misuse recurring history.

12. Pretreatment assessment of Hepatic Function is mandatory.
Adult
 Initial 40mg/day, may increase to 80mg/day (after 3 days) up to 100mg/day
(maximum dose)
 May be withdrawn without tapering
 Pediatrics (>6yrs of age):
 Initial 0.5mg/kg/day may increase to 1.2mg/kg/day
 Maximum 1.4mg/kg/day or 100mg/day whichever is less.
 Dose adjustment is required in hepatic impairment.

13.  Xerostomia (dry mouth)
 Headache
 Insomnia
 Decreased appetite
 Weight loss
 Vomiting
 Suicidal ideations
 Hypertension
 Erectile dysfunction
 Hepatic failure

14. Hypersensitivity
Hypertension
Angle closure glaucoma
Pheochromocytoma
Severe cardiac or vascular disorders

15.  Appropriate contraception is recommended for sexually active women
of childbearing potential (Heiligenstein 2003).
 Consider discontinuing or changing treatment in women who become
pregnant during atomoxetine therapy (Larsen 2015).
 An agent other than atomoxetine is preferred for the treatment of
attention-deficit/hyperactivity disorder (ADHD) in women who are
breastfeeding (Larsen 2015).

16.  Not registered in Nepal.
 Available in India.
 Brand names: Attentrol (Sun), Axepta (Intas)
 Price: Approximately 10rs/10mg tablet

17.  Atomoxetine is similarly efficacious compared to Methylphenidate and other
available options.
 Its low abuse potential and relatively low cost as compared to stimulants
makes it a good choice in number of situations.
 It can be combined with Stimulants if monotherapy is not efficacious.
 More readily available than stimulants in neighboring country gives us
opportunity for prescription.

18. Triangle Principle of treatment of ADHD
Pharmacotherapy
Parent Education &
Behaviour Therapy
School Instructions

19. 2 major Principals:
Encouraging and rewarding good behavior
(positive reinforcement).
Removing rewards by following bad behavior
with appropriate consequences, leading to the
extinguishing of bad behavior (punishment)

20.  Decide ahead of time which behaviors
are acceptable and which are not.
 Define the rules, but allow some
flexibility
 Manage aggression; Time out
 Create structure
 Break tasks into manageable pieces
 Simplify and organize your child’s life
 Limit distractions
 Encourage exercise
 Regulate sleep patterns
 Encourage out-loud thinking
 Promote wait time
 Calm yourself

21. Social skills training
Communication training
Family therapy
School-based interventions
Behavioral peer intervention

22.  Kaplan and Sadocks Comprehensive text Book of Psychiatry, Tenth edition, BJ Sadock et al.
 Stahl’s Essentials of Psychopharmacology, Fourth Edition, SM Stahl
 Atomoxetine; A Review of its Use in Attention-Deficit Hyperactivity Disorder in Children and Adolescents; Karly P.
Garnock-Jones et al, 2009
 Comparative efficacy and safety of methylphenidate and atomoxetine for attention-deficit hyperactivity disorder in children
and adolescents: Meta-analysis based on head-to-head trials Qiang Liu Et. Al. 2017
 Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine, bupropion and methylphenidate in treatment of
attention deficit hyperactivity disorder in children and adolescents: A meta-analysis with focus on bupropion; Matej Stuhec
et. Al. 2015
 Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents,
and adults: a systematic review and network meta-analysis; Samuele Cortese et. al. 2018; The Lancet
 Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine, bupropion and methylphenidate in treatment of
attention deficit hyperactivity disorder in children and adolescents: A meta-analysis with focus on bupropion Matej Stuhec
et al 2015
 Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: Update on
recommendations from the British Association for Psychopharmacology Blanca Bolea-Alamañac, 2017
 UpToDate