ADHD Flashcards
Diagnosing ADHD
-Symptoms must be present before the age of 12; cannot diagnose before age 3.
-Impairment present in at least 2 different settings
-Evidence of functional interference: Socially, Academically, or in Extracurricular activities
-Subtypes = Inattentive, Hyperactive/Impulsive, and Combined
ADHD “causes”
-Genetic (75%)
-Delayed maturation of prefrontal cortex circuitry
-Ineffective “tonic” NE and DA neurotransmission/hypoactivity of dopamine and norepinephrine pathways in brain regions such as the prefrontal cortex (PFC)
ADHD Comorbidities
Comorbidities result from inadequate tuning in the VMPFC
Conditions: Learning disability, anxiety disorder, mood disorder, conduct disorder, oppositional defiant disorder, substance use disorder
Nicotine use in ADHD
Nicotine enhances DA release and enhances arousal –> subjective improvement of ADHD symptoms.
ADHD smoke 2x more compared to non-ADHD population.
ADHD medications primarily target _____ symptoms.
hyperactivity and impulsivity
Dopamine reward system
Bursts of firing by DA = phasic DA stimulation is thought to reinforce learning and reward conditioning
Known to fire when: education, recognition, career development, enriching social/family connections, other enriching experiences
ADHD Inattentive subtype
capacity for executive function is impaired, selective attention, difficulty with sustained attention and problem solving
Hyperactive/impulsive subtype
get into more trouble
ADHD Tx
- Assess/manage substance abuse problems
- Treat mood and anxiety
- Evaluate for other common ADHD comorbidities
- Stimulants or non-stimulants
ADHD Stimulants
Methylphenidate (Ritalin, Concerta): increases synaptic levels of DA and NE through selective inhibition of presynaptic transporters
Dextroamphetamine/Amphetamine Salts (Adderall, Vyvanse): cause release of DA, NE, and 5-HT into the synapse
ADHD Non-stimulants
Guanfacine (Intuniv)
Clonidine (Catapres)
Viloxazine (Qelbree)
Atomoxetine (Strattera)
Wellbutrin (Bupropion)
Contraindications to Stimulant Use
-Known cardiac abnormalities
-Moderate to severe hypertension
-Hyperthyroidism
-Motor tics & Tourette’s Syndrome
-Glaucoma
-Agitation
-Anxiety
-History of drug abuse
-Concurrent MAOI within 14 days
*Strattera contraindicated in hypertension and glaucoma
Pediatric ADHD Tx
- Behavioral therapy for children 5 years and younger
- Dextroamphetamine & amphetamine salts for 3 years and older
- Methylphenidate for 6 years and older
Tx monitoring ADHD
-Physical exam (height, weight, BP, pulse); height & weight 1-2x per year for kids
-Monitor for adverse effects and adjust medication dose/timing
-Monitor for therapeutic response initially every 1-2 weeks and then every 1-3 months
-Assess both behaviors and academic achievements
-Meds no longer needed if: No symptoms for 1 year, No need for medication adjustment, Lack of deterioration after missed dose
-Consider timed trial off meds during low stress time
Neurobiology of Inattention
Executive dysfunction and linked to inefficient information processing in the dorsolateral prefrontal cortex (DLPFC)
Sustained attention is hypothetically modulated by a cortico-striato-thalamo-cortical loop that involves the dorsolateral prefrontal cortex (DLPFC) projecting to the striatal complex. Inefficient activation of the DLPFC can lead to difficulty following through or finishing tasks, disorganization, and trouble sustaining mental effort
Neurobiology of Selective attention
Inefficient information processing in the dorsal anterior cingulate cortex (dACC).
Selective attention is hypothetically modulated by a cortico-striato-thalamo-cortical loop arising from the dorsal anterior cingulate cortex (dACC) and projecting to the striatal complex, then the thalamus, and back to the dACC. Inefficient activation of dACC can result in symptoms such as paying little attention to detail, making careless mistakes, not listening, losing things, being distracted, and forgetting things
Neurobiology of Impulsivity
Impulsivity is associated with a cortico-striato-thalamo-cortical loop that involves the orbital frontal cortex (OFC), the striatal complex, and the thalamus. Examples of impulsive symptoms in ADHD include talking excessively, blurting things out, not waiting one’s turn, and interrupting
Neurobiology of hyperactivity
Motor activity, such as hyperactivity and psychomotor agitation or retardation, can be modulated by a cortico-striato-thalamo-cortical loop from the prefrontal motor cortex to the putamen (lateral striatum) to the thalamus and back to the prefrontal motor cortex. Common symptoms of hyperactivity in children with ADHD include fidgeting, leaving one’s seat, running/climbing, being constantly on the go, and having trouble playing quietly.
ADHD: DA and NE
Excessive noradrenergic neurotransmission can lead to impaired working memory due to stimulation of α1 (and β1) receptors. Excessive dopaminergic neurotransmission can lead to overstimulation of D1 receptors in the prefrontal cortex
Prefrontal motor cortex is linked to ___________ symptoms
hyperactive
Orbitofrontal cortex is linked to _________________symptoms
impulsive
DLPFC is linked to ___________ symptoms
sustained attention and problem solving
dACC is linked to ___________ symptoms
selective attention
Mesocortical Dopamine Pathway
Projects to the prefrontal cortex and is responsible for modulating attention and executive function
Stimulant mechanism of action
Block the reuptake of dopamine and norepinephrine in the synapse, increasing their availability and improving attention and focus.
They can also promote increased release of dopamine and norepinephrine from presynaptic neurons
Amphetamines mechanism of action
Competitive inhibitor and pseudosubstrate for NETs and DATs, binding at the same site that the monoamines bind to the transporters, thus inhibiting NE and DA reuptake
Stimulant therapeutic effects
Effective at reducing core symptoms of ADHD, such as inattention, hyperactivity, and impulsivity.
They enhance cognitive control, task persistence, and working memory.
Stimulant side effects
Insomnia, reduced appetite, weight loss, irritability, and potential for increased anxiety. Cardiovascular side effects such as increased heart rate and blood pressure.
Stimulant risk for abuse
due to their ability to increase dopamine levels in reward pathways (e.g., mesolimbic dopamine system)
Atomoxetine (Strattera)
Non-stimulant. A norepinephrine reuptake inhibitor (NRI) that selectively blocks the norepinephrine transporter, increasing norepinephrine levels in the PFC.
Does not have dopaminergic effects in the striatum or nucleus accumbens, thus it has low abuse potential compared to stimulants.
Guanfacine (Intuniv) and Clonidine (Kapvay)
Non-stimulant. Alpha-2A adrenergic agonists that enhance prefrontal cortical function by strengthening working memory, impulse control, and attention through increased norepinephrine signaling. Clonidine is approved to treat hypertension and ONLY controlled-release Clonidine is approved for ADHD
Often used as adjunctive therapy with stimulants or as a second-line treatment.
Viloxazine ER
Non-stimulant. Inhibitor of the norepinephrine transporter (NET) and also has actions at serotonin 2B (5HT2B) and 5HT2C receptors
