ADHD Treatments - Amphetamines & Others

What is Attention Deficit/Hyperactivity Disorder (study)

• Tiktok study

  • about ½ had incorrect info

  • small % was accurate

What is ADHD/ADD?

• a mental disorder, normal human differences, or a behavioral problem due to environmental demands?

  • other controversies: over-diagnosis; is there a late-onset (adult) type? wisdom of prescribing stimulants to children? (short-or long-term)

• Type types:

  • inattention

    • lack of attention to details/careless mistakes

    • difficulty sustaining attention

    • does not seem to listen

    • does not follow through on instructions (easily sidetracked)

    • difficulty organizing tasks and activities

    • avoids sustained mental effort

    • loses and misplaces objects

    • easily distracted

    • forgetful in daily activities

  • hyperactivity/impulsivity

    • fidgetness (hand or feet)/squirms in seat

    • leaves seat frequently

    • running about/feeling restless

    • excessively loud or noisy

    • always “on the go”

    • talks excessively

    • blurts out answers

    • difficulty waiting his or her turn

    • tends to act w/o thinking

  • ≥ 5 symptoms per category in adults, ≥ 6 mos; age of onset ≤ 12 years; noticeable in ≥ 2 settings; impact on social, academic, or occupational functioning; not better accounted for by another mental disorder

ADHD: Over Diagnosis in Young Children? (Study)

• are young children overdiagnosed bc they are put in school @ younger age & difference in month of enrollment

  • spike in Aug/Sept cohort → some of kids are over-diagnosed

  • states w/ Sept 1 cut off → same spike

  • states w/o Sept 1 cutoff → no spike

• overall => leads to overdiagnosis in cohort

What is ADHD? (Study)

• healthy controls: while engaged in task → DLPFC more engaged; VMPFC inengaged

• ADHD: w/o meds → no engagements in DLPFC

• ADHD: w/ meds → engagement in DLPFC & less enagagement in VMPFC

• overall => ADHD meds → normalize functioning in brain of PFC

  • stimulate brain areas of PFC that help w/ control & inhibition (i.e., DLPFC)

ADHD & “Mind Wandering”

• related to DMN

  • attention can shift from outward to inward

• Default Mode Network (inward): (wander)

  • PCC: posterior cingulate cortex

  • vmPFC: Ventromedial PFC

• Central Executive Network (outward): (focus)

  • dlPFC: dorsolateral PFC

  • PPC: posterior parietal cortex

• Salience Network (switch): (dynamic switching; salience - means something that catches your attention)

  • AIC: anterior insular cortex

  • ACC: anterior cingulate cortex

• someone w/ inattention ADHD = spends too much time in DMN

• either CEN underdeveloped or DMN overactive or dysfunctional SN

• ADHD meds = supress DMN & stimulate CEN

Most Prescribed Psychiatric Medications

• ADHD Pharm Approaches

  • stimulants:

    • amphetamines

    • methylphenidate

  • non-stimulants

    • atomoxetine

    • guanfacine clonidine (adjuncts)

Medications Available for ADHD

• lots of versions of methylphenidate = durations ~4 hrs - Ritalin

  • short duration

• mixed amphetamine salt (Adderal) = ~8 hrs

• Non-stimulants - long durations → small doses

  • can be used in addition to stimulants

Stimulants: methylphenidate (Ritalin)

• methylphenidate (Ritalin): in some form = 90% of marketed ADHD meds

  • 70% of children show improved behavior & learning ability

• PharmK: short 4 hrs. duration creates potential end-of-dose rebound in dysfunction

• PharmD: as a DRI, blocks DATs to increase DA levels, esp. in DLPFC

• methylphenidate (Concerta): coated w/ immediate-release methylphenidate → (push medication out of push compartment)

  • tablet contains “osmotic pump” system for gradual release over 10-hrs

  • tablet remains intact, leaves GI tract as an empty shell

ADHD Treatment - Don’t Forget Therapy!

• Multimodal Treatment of ADHD

  • sponsored by NIMH

  • N = 579 children (ages 7-10) diagnosed w/ ADHD, lasting 14 mo.

  • random assignment @ each clinic to 1 of 9 treatments

1. Medication management (mostly methylphenidate)

2. Behavioral Therapy

3. Combined Medication + Behavioral Therapy

4. Community Care (assessment & resource information)

• Results: (Children Successfully Treated)

  • Medication group = 56%

  • Behavioral Therapy group = 34%

  • Combo Treatment Group = 68%

• Combo is best

Stimulants: Amphetamines for ADHD

• Remember amphetamine PharmD?: NE & DA releasing agents

• mixed amphetamine salts (Adderall): dextro-amphetamine & amphetamine

  • mostly widely prescribed ADHD meds

  • typical side effects: reduced appetite, headache, insomnia, elevated BP/HR

  • rare and/or serious side effects: anxiety, psychosis, hostility, depression (esp. on withdrawal)

  • long-term effects on growth or brain development unclear

• Lisdexamfetamine (Vyvanse): prodrug approach, dextroamphetamine + amino acid L-lysine (RBCs metabolize into active drug); compared to Adderall

  • slower absorption (1-2 hrs vs. 30 min.), longer duration (14 hrs vs. 8-10 hrs)

  • likely lower abuse & addictive potential than Adderall

Non-Stimulants Medications: atomoxetine (Strattera)

• up to 30% of ADHD patients don’t respond well to stimulants

  • also, some parents/children uncomfortable w/ stimulants use

  • some non-stimulant meds are available

• atomoxetine (Strattera): FDA approved 2002

  • 1st SNRI (Selective NE Reuptake Inhibitor) approved for ADHD in children & adults

  • can be used w/ co-morbid ADHD/MDD; off-label use for treatment-resistant MDD

  • cross-tolerance w/ SSRIs may require dose adjustment

  • more effective in treatment-naive patients than there previously on stimulants, so it’s a better “first-line” drug before any potential more to stimulants

Non-Stimulant Medications (clonidine & quanfacine)

• NE agonists are thought to ultimately decrease NE release (via PharmD tolerance)

  • “downstream” effect of increase in DA release in PFC

  • common side effects: sedation & fatigue

• “Second-line” treatments/adjuncts to stimulant-based ADHD medications

• clonidine: old drug (1960s) for high BP

  • approved by FDA (2010) for ADHD under brand name Kapvay

• guanfacine (Intuniv): longer half-life, less sedating than other NE agonists

  • combining guanfacine with stimulant meds offers greater ADHD symptom improvements than either as monotherapy