Case: Presenting complaint

 9 year old male referred from Australia for medication prescription.

 History of ADHD (combined type)- diagnosis considered since 2015
 Has not been on medications since last November.
 Coped with a recent overseas holiday.
 WISC-V
 Borderline verbal comprehension and working memory, low average fluid reasoning and
processing speed, and average visuospatial index.
 Conners assessments
History of presenting complaint continued

 Emotion dysregulation; difficulties with verbal expression

 Aggressive outbursts
 Heat triggers difficulties with behavioural regulation
 Some difficulties at home e.g. rough with sister
 Impaired awareness of social cues.
 Behind with school
 Some anxiety about going out but does not stop him doing things.
Past treatment

 Started medications in April 2018 (10 mg Methylphenidate SA at 8 am and 11 am)

  improved academic performance; more awareness of his emotions; sometimes asks for
medication when he feels he is not able to control himself
 Increased to methylphenidate IR 30 mg mane and 20 mg midi
 Play therapy
 Emotional regulation course
 Likes blu tack, playdough, chewing gum,
 Support from teacher aides and Reading Recovery Programme
Medications

 Methylphenidate LA 60 mg OD
Past medical history

 Recent left distal radius fracture

 Birth history
 Born at 38/40 in NZ via EMCS for foetal distress
 Gestational diabetes
 No neonatal issues or developmental concerns
 Issues with social interaction noticed in kindergarten
 Anxiety- trialled sertraline but this caused agitation and poor sleep
 Sometimes falls asleep at school- awaiting results of sleep study
Social and family history

 Lives with parents and sister

Examination

 Well-grown
 Height 154.5 cm (99.9th centile)
 Weight 61.2 kg (>99.9th centile)
 BP 114/86
Management

 Discuss appropriate treatment and dosing with Dr Colin Watt (CAMHS)

 IQ test to identify eligibility for extra support.
Clinical question

 What is the most effective pharmacological treatment for ADHD?

ADHD etiology

 Genetic and environmental influences

 Prematurity
 Prenatal alcohol and tobacco exposure
 Gene environmental interactions e.g. polymorphisms in dopamine transporter gene and
deprivation

 Animal studies suggest it is related to imbalance between norepinephrine and dopamine

systems in the prefrontal cortex.
Available treatments

 Methylphenidate
 Amphetamines: e.g
dexamphetamine,
lisdexamfetamine
 Atomoxetine (Strattera)
 Alpha-2 adrenergic agonists:
e.g. clonidine, guanfacine
Up to Date

 Stimulants (methylphenidate and amphetamines) first line.

 Amphetamines may be slightly more effective than methylphenidate but less well
tolerated.
 Often start with short acting formulations in case there are adverse effects.
 Variable dose-response relationship with stimulants.
Pubmed search results – paper 1
Pubmed search results- paper 1

 Search strategy: PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Register of
Controlled Trials, EMBASE, ERIC, MEDLINE, PsycINFO, OpenGrey, Web of Science
Core Collection, ProQuest Dissertations and Theses (UK and Ireland), ProQuest
Dissertations and Theses (abstracts and international), and the WHO International Trials
Registry Platform, including ClinicalTrials.gov, from the date of database inception to
April 7, 2017
 Population: children, adolescents, and adults with ADHD
 Intervention: ADHD medications
 Comparison: placebo
 Outcome: change in severity of clinician or teacher reported core ADHD symptoms
Results
Results
Results
Conclusions

 Stronger evidence for stimulants than non-stimulants.

 Methylphenidate best for children.
 Amphetamines best for adults.
Pubmed search- paper 2
Paper 2

 Search strategy: Electronic literature search of CENTRAL, MEDLINE, PreMEDLINE,

CINAHL, EMBASE, PsychINFO, Scopus and Web of Science for articles published in
the English language between 1950 and 2012. Reference lists of included studies were
checked for additional studies.
 Population: patients < 18 years
 Intervention: SA methylphenidate
 Comparison: LA methylphenidate
 Outcome: improvement of core ADHD symptoms; adverse effects
Results

 13 RCTS were included

 Meta-analysis of three studies which used parent ratings to report on
hyperactivity/impulsivity had an standardized mean difference of −0.30 (95% CI −0.51 to
−0.08) favouring the long-acting forms.
 Three studies used teacher ratings to report on hyperactivity and had a standardized mean
difference of 0.29 (95% CI 0.05 to 0.52) favouring the short-acting methylphenidate.
 Slightly more adverse events reported with long acting vs short acting (578 vs 566).
Conclusions

 Long-acting forms have a modest effect on the severity of inattention/overactivity and

hyperactivity/impulsivity according to parent reports.
 Short-acting methylphenidate was preferred according to teacher reports.
Pubmed search results- paper 3
Paper 3

 Search strategy: PubMed, Embase, and Cochrane library from their inception to April
2016 to select head-to-head trials that compared atomoxetine and methyphenidate in
children and adolescents.
 Population: children and adolescents
 Intervention: methylphenidate
 Comparison: atomoxetine
 Outcome: response rate, ADHD Rating Scale (ADHD–RS) score, and adverse events
Results
Conclusions

 Methylphenidate is more effective than atomoxetine: higher response rate and reduced
inattention plus lower risk of side effects apart from insomnia.
Pubmed search results- paper 4
Paper 4

 Systematic search through the ClinicalTrials.gov database and Pubmed for registered
RCTs of novel ADHD medications from 1 January 2014 to 31 December 2018
 Population: children, adolescents, or adults with a formal diagnosis of ADHD.
 Intervention: novel medications with potential for treatment of ADHD
 Comparison: controls without ADHD
 28 RCTs were identified.
Paper 4

 Serotonin–norepinephrine–dopamine reuptake inhibitor

 Centanafidine
 Selective norepinephrine reuptake inhibitor
 Viloxazine
 Selective HT agonist
 Vortioxetine
 Fasoracetam
 Metadoxine
 Mazindol
References

 1. Cortese S, Adamo N, Del Giovane C, Mohr-Jensen C, Hayes AJ, Carucci S, et al. Comparative efficacy and tolerability of medications for
attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. The Lancet Psychiatry.
2018;5(9):727-38.
 2. Liu Q, Zhang H, Fang Q, Qin L. 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. Journal of Clinical and Experimental Neuropsychology. 2017;39(9):854-65.
 3. Nageye F, Cortese S. Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD. Expert
review of neurotherapeutics. 2019;19(7):707-17.
 4. Punja S, Zorzela L, Hartling L, Urichuk L, Vohra S. Long-acting versus short-acting methylphenidate for paediatric ADHD: a systematic review
and meta-analysis of comparative efficacy. BMJ Open. 2013;3(3):e002312.
 5. da Silva BS, Cupertino RB, Rovaris DL, Schuch JB, Kappel DB, Müller D, et al. Exocytosis-related genes and response to methylphenidate
treatment in adults with ADHD. Molecular Psychiatry. 2018;23(6):1446-52.
 6. Stevens SE, Kumsta R, Kreppner JM, Brookes KJ, Rutter M, Sonuga-Barke EJS. Dopamine transporter gene polymorphism moderates the effects
of severe deprivation on ADHD symptoms: Developmental continuities in gene–environment interplay. American Journal of Medical Genetics Part B:
Neuropsychiatric Genetics. 2009;150B(6):753-61.
 Up to Date
Thank you 