ADHD

Prevalence of AHD

8% school-aged children (half are medicated)

Most common mental disorder aged 4-17 years

3M:1F.

Subtypes/ presentation of ADHD

1. inattentive

2. hyperactive

3. impulsive

Risk factors for ADHD

Genetic (parental ADHD) ↑8 x RR

Psychosocial adversity/trauma ↑4 x RR

Prematurity, ↓Birth Weight, early onset Sx

Smoking & alcohol use during pregnancy

Sleep deprivation, toxins (eg lead, ↓Fe?)

Head trauma (& LOC) in early childhood

↑ competing interests (screens, highschool commitments - multiple teachers, classes, timetables, homework etc)

Food additives/sugar diets controversial ('Media Diet')

Effect of adolescent risk-taking behaviour/co-morbidities

Diagnosis ADHD

Adults need fewer Dx criteria (5 vs 6 in children)

Diagnosis <6 difficult

Teacher & Parent Rating Scales not diagnostic

DSM-5: Symptoms must be:

- Present in ≥2 settings (if only present in 1 -> behavioural)

- Persist for >6 months

- Onset before age 12

- Impair academic, social, or occupational functioning

- Maladaptive & inconsistent with child's development

- Another diagnosis can't account for the symptoms

Differential: fetal alcohool Spectrum disorder, autism spec disorder, childhood absence epilepsy (inattentive sx), hearing/visual impairment

Comorbidities ADHD

30-50% motor coordination difficulties (dyspraxia, clumsy, etc)

>20% have pre-existing tics (before medication)

>1/3 have comorbid mental health conditions e.g. ODD (most common), learning, substance-use, psychoaffective disorders, conduct disorder

Comorbidities may mask ADHD

Treating ADHD makes the co-morbidities easier to treat

Hypervigilance counteracts inattention (but ↑ cognitive fatigue)

Inattentive ADHD overview (presentation, sx, development into adulthood)

Presentation:

- Peak at 8-9

- Most in girls

- Harder to detect and treat

Sx:

- Poor concentration & attention to detail (ADD)

- Disorganised, loses or misplaces things

- Forgetful, easily distracted, 'zones out'

- Difficulty with multi-stage commands

- Never completes project

Development:

- Persists into adulthood

- Academic underachievement

Hyperactive ADHD overview (presentation, sx, development into adulthood)

Presentation:

- Peak at 7-8

- Most in boys

Sx:

- Restless ("on the go")

- Excessive fidgetiness/ talking

- Can't remain seated in class

- Runs/climbs excessively

- Can't play quietly

Development:

- Hyperactivity reduces after adolescence

- Restlessness generally persists into adulthood

Impulsive ADHD overview (presentation, sx, development into adulthood)

Presentation:

- Peak at 7-8

- Most in boys

Sx:

- Difficulty awaiting turn, rushes work, messy handwriting

- Acts without thinking, can't work slowly /systematically

- Unintentional injury to self or others ('accident prone')

- Inability to resist temptation and opportunities ('dares')

- Intruding or interrupting others

Development:

- generally persists into adulthood

consequences of ADHD

Doubles mortality risk (adult,♀>♂) - violence, crime, ↓ health, risky behaviour/ accidents

More likely to be unemployed, unskilled, lower salary

4-fold higher STI rates

Higher teenage pregnancy rates

↑ risk: social and financial instability, welfare dependent, drug (especially cannabis) & alcohol abuse, workplace injury, MVA, Lack of fear awareness, ↑societal costs, ↑comorbidities, vulnerability, ↓self-esteem, taken advantage of by others, easily swayed, 'conned', marital discord/separation

DA and NA role in prefrontal cortex

DA role - Attention (stimulation/motivation), alertness, vigilance, ↑Goal-directed behaviour (reward, computer games), executive functioning (problem solving, working memory, cognitive flexibility, abstract reasoning & planning)

NA role - arousal (staying awake/on task), excitability (tonal), regulation (response to danger/opportunity), memory storage & retrieval (esp emotions)

ADHD = ↓DA & NA neurotransmission

DA role in nucleus accumbent

DA pathways - aversion, motivation, pleasure, reward, reinforcement of learning, addiction, motor planning (coordination), impulsivity

Major inputs include PFC amygdala & VTA via mesolimbic pathway (DA)

No NA neurones so atomoxetine = no addictive effects

1st line for ADHD

Pharmacological:

1. Psychostimulants: DAT inhibitor (dex, lisdex, methylphenidate)

2. Non-psychostimulants: Atomoxetine (NAT inhibitor), or ⍺-2A adrenoceptor agonists (guanfacine, clonidine)

3. Complementary Therapies (omega 3, vitamins/minerals, saffron)

Methylphenidate MOA, onset, dose (psychostimulant)

MOA:

1. Increase extracellular/ synaptic DA and NA by reversibly inhibiting DA, NA transporters (DAT, Nat)

2. Mild 5HT1A and alpha-R agonist

2 enantiomers d-MPH and l-MPH

- d-MPH is a bit more active

- Aus comes in racemic mixture

Onset: 20 mins, peak at 2 hours

Duration of action: 4 hours, Long acting: 8 hours

Dose: Approved dose range: 1-2 mg/kg/day. Max PBS cut off 72 mg/day. Maximum 60 mg for IR

Ritalin-LA capsules: 50% IR, 50% delayed release beads with polymer coating (about 4 hours)

Concerta: control release tabs

Dexamphetamine MOA, onset, dose (psychostimulant)

MOA:

1. Increase extracellular/ synaptic DA and NA by reversibly inhibiting DA, NA transporters (DAT, Nat)

2. ↑ DA and NA release (pre-stored) & ↓ storage of DA and NA vesicles -> potential stronger effect

Onset: 30 mins, peak in 2-3 hours

DOA: 6-8 hours

Dose:

0.5-1 mg/kg/day

Max 50 mg/day

5mg tabs - may require lots of tabs!!

Doses more than 50 mg/day needs stimulant subcommittee approval

Lisdexamphetamine MOA, onset, dose (psychostimulant)

MOA:

1. Increase extracellular/ synaptic DA and NA by reversibly inhibiting DA, NA transporters (DAT, Nat)

2. ↑ DA and NA release (pre-stored) & ↓ storage of DA and NA vesicles -> potential stronger effect

Onset: Inactive Prodrug (1h to be activated by RBCs)

DOA: 2-13 hours, no peak effect (long DOA increase insomnia risk)

Dose to clinical effect

Start: 30 mg/day

Usual range: 15-70 mg/day

20, 30, 40, 50, 60, 70 mg caps.

- independent of weight

Most patients lose weight: (7% ↓initial BW in 1 yr)

Boys often dislike pink 30 mg cap (50 mg is blue)

PBS Approved >25

May be opened & dissolved

Less potential for abuse: longer DOA + needs to be converted to active drug by RBC as well (same effect in inhaled or injected

Psychostimulant AE

COMMON: insomnia, ↓appetite, anorexia, weight loss, labile mood, headache, tics (MPH)...OR NONE

Usually at initiation/dose increase

May adjust to SE if at same dose for 2-3 weeks

Usually need appetite/weight loss for benefit/effect

Height may be delayed by <2 cm/year for first 3 years use - but due to disease or meds?

Transient ↑ BP and HR - generally safe CV profile, ECG/ Cardiology review if heart condition

↕ Tics & psychostimulants (no clear evidence)

Atomoxetine (non-psychostimulant)

MOA:

- Selective NAT inhibitor (prevents NA reuptake)

- Acts at PFC only

- Non-stimulant, no dopaminergic action, not an antidepressant

Indication:

3rd line after methylphenidate & DXPH/LDX

>6 yrs (PBS)

- Ideal for comorbid anxiety, substance use, tics, Tourettes, poor growth/mood/sleep on stimulants

Dose:

0.5 mg/kg/day for 3 days, then 1.2 mg/kg/day for 1-2 weeks to 1.4 mg/kg/day

Max 100 mg/day

PP:

- Do not open capsules (ocular irritant)

- Dyspepsia & dizziness common for first wk

- Takes 6-9 wks to work

- Beware CYP2D6 - Inhibitors (eg fluoxetine) to max 80mg

- 6% Caucasians: slow CYP2D6 metabolisers

- Risk of suicidality (if not already suicidal)

- Not on PBS if combined with psychostim Rx

Guanfacine (non-psychostimulant)

MOA:

- Selective α2A-R agonist

↑ cognition, ↑ working memory, ↓ distractibility, ↑ behavioural inhibition, ↑ verbal fluency

Indication:

Start 6-18 yrs (PBS)

Mono/adjunct psychostimulant Rx (0.05-0.12mg/kg/day)

Dose:

Start 1 mg/day, +1mg/week titration → 1-7 mg/day (monotherapy)

Max 4 mg (dual therapy)

1, 2, 3 & 4 mg tabs (7 or 28 packs)

PP:

- Avoid fat, grapefruit

- Swallow whole (SR), peak ~5hr, t1⁄2~18hr

- CYP3A4 metab (↑valproate, rifampicin↓, ketoconazole↑)

- AE:↓HR/BP, ↑weight/sleep (opposite to stimulants)

Adverse driving effects - may continue into but not started in adulthood

Lactose

Non-pharm for ADHD

Lifestyle:

- ↑ Organisation: timetable, calendar/apps, scaffolding

- Sleep: ↑Short & Long-term Memory, CBT, routine

- Exercise: sensory, balance, HIIT, yoga, tai chi, karaté

Cognitive: 'Brain-training' (eg CogMed, Luminosity)

- Mindfulness may ↑cortical thickness in ADHD (structural ∆)

Diet: increase Breakfast, Protein, ↓GI, Fe if low, intolerance?

- If ↓eating: ↑calories, ∆meds, holidays, adjuvant (α-ag)

Supplements - Omega 3 ~3g/day for 3/12, (↑Mg, Zn)

Saffron for ADHD

MOA:

1.

2. Inhibits DA & NA reuptake (also NMDA-R antagonist & GABA-α agonist)

Claimed actions: anti-inflammatory, antioxidant, antitumour, nootropic, anticonvulsant

EFFICACY: similar efficacy at 6 weeks, fewer AE:

Saffron ~ 1 mg/kg/day

Methylphenidate <1 mg/kg/day

EXPENSIVE