Pharmacological Treatments for ADHD

Attention Deficit Hyperactivity Disorder (ADHD)

• ADHD is classified as a developmental disorder by the DSM-5.
• Disorders initially appearing in children are often labeled as developmental disorders.
• The defining feature of ADHD is a persistent pattern of inattention and/or hyperactivity-impulsivity.
• These symptoms must significantly impact developmental processes.

Neurotypical Behavior

• Expecting a five-year-old to sit through a lecture is not neurotypical behavior.
• Age-related improvements in memory and attention are evident.
• Executive functions, like following directions, raising hands, waiting, and adhering to rules, progressively develop.

Introduction to ADHD

• ADHD is a persistent pattern of inattention and/or hyperactivity-impulsivity.

Diagnosis of ADHD

• ADHD is diagnosed as one of three types: inattentive, hyperactive/impulsive, or combined.
• Diagnosis is based on criteria outlined in the DSM-5-TR.
• Symptoms must have been present for at least six months, with an onset typically before age 12.

Inattentive Type

• Easily distracted by extraneous stimuli.
• Difficulties concentrating on tasks and activities, such as lectures, conversations, or extended reading.
• Appearing not to listen directly when spoken to.
• Not following through on instructions or completing tasks or duties.
• Struggling to organize tasks and work, resulting in disorganized work and missed deadlines.
• Avoiding or disliking tasks requiring sustained mental effort, such as report-writing or form completion.
• Repeatedly losing necessary items for tasks or daily activities, such as school supplies, keys, wallets.
• Making careless mistakes in tasks due to a lack of attention to detail.
• Forgetting daily tasks, such as chores or errands.

Hyperactive/Impulsive Type

• Fidgeting, tapping hands or feet, or squirming in seat.
• Inability to remain seated in appropriate settings (like classrooms or workplaces).
• Running or climbing inappropriately.
• Excessive talking, interrupting others, or intruding on others' conversations or activities.
• Difficulty waiting for one's turn.

Combined Presentation

• A combined presentation of ADHD involves symptoms from both inattentive and hyperactive/impulsive types.
• To meet this criteria, there needs to be 6 valid symptoms from both categories A1 and A2.

Key Features of ADHD

• Symptoms must present in multiple settings (e.g. school, home).
• Signs of the disorder may be less noticeable with close supervision, frequent rewards for good behavior, in a new setting, or when the individual is engaging in a stimulating task.
• ADHD often impacts academic performance and can lead to social rejection.
• Other comorbid disorders like ASD or OCD are common with ADHD.
• ADHD is generally not considered an intellectual disorder, though mild delays in language, motor, and social development can occur.
• Delays could be secondary to not paying attention to things.

Prevalence of ADHD

• Prevalence is approximately 7.6%.
• Significantly higher proportion of males with ADHD compared to females (approx 3:1 ratio).
• Adult ADHD prevalence is up to 2.5%.
• ADHD symptoms can decrease in intensity over time but often remain persistent in 30–50% of cases.
• Impulsiveness and hyperactivity tend to diminish more quickly than inattention.
• Prevalence can vary geographically, with some areas exhibiting higher rates compared to others.

Prevalence of ADHD: Importance of Culture

• Diagnosis of ADHD is impacted by cultural context.
• Current diagnostic criteria are largely based on observations of elementary school-aged North American boys.
• Hyperactivity and inattentiveness might not be concerning in cultures where formal schooling isn't a consistent feature.
• High levels of academic achievement and competition, in some societies, may cause minor levels of inattentiveness or impulsivity to be viewed as problematic or pathological.
• Diagnostic criteria and the manifestation of the disorder vary significantly based on the environment, social and academic expectations/criteria.
• ADHD symptoms and their impact can differ across various cultures and contexts.

Comorbidity of ADHD

• About two-thirds of children diagnosed with ADHD also have at least one other DSM disorder, or co-morbidity.
• Common comorbidities include oppositional defiant disorder, tic disorders, conduct disorders, mood disorders and anxiety.

What Causes ADHD?

• Genetic factors are significant in ADHD etiology; estimates suggest heritability for ADHD is up to 80%.
• Strong genetic overlap exists with Autism Spectrum Disorder.
• Research has not fully identified specific genes responsible for ADHD.
• Weak associations have been identified with genes associated with dopamine reuptake transporter and the D4 dopamine receptor.

Environmental/Developmental Risk Factors

• Gene-environment interactions influence ADHD manifestation.
• Exposure to environmental factors (like smoking during pregnancy) may influence the severity of ADHD symptoms.
• Perinatal Hypoxia, (low oxygen availability) around birth is linked to ADHD risk.
• Food coloring or preservatives are not directly linked to ADHD in population-level studies. Though sensitivity in certain populations may affect behavior.

Behavioral Markers of ADHD

• Children with ADHD exhibit behavioral markers such as difficulty waiting for a second moment or turn.
• "Go, No-Go" tasks and the Iowa Gambling Task can help to highlight issues with behaviors related to impulsivity and risk assessment in individuals with ADHD.

Brain Areas Implicated in ADHD

• Dorsolateral prefrontal cortex (DLPFC)
• Ventrolateral prefrontal cortex (VLPFC)
• Parietal cortex
• Midcingulate cortex
• Striatum (Caudate and Putamen)
• Cerebellum
• Alerting network comprised of Frontal cortex, Parietal cortex and Thalamus
• Frontostriatal Circuit comprised of Ventral anterior cingulate cortex, Dorsal anterior cingulate cortex, Putamen, Nucleus Accumbens, Amygdala, and Caudate nucleus

How Exactly Are These Brain Areas Affected?

• Individuals with ADHD often exhibit lesser influence from rewards compared to neurotypical individuals.
• Deficits in executive functions and reward areas (such as the frontostriatal circuits) are often present.
• Also, weaknesses in inhibitory control mechanisms in behavior are often highlighted.

Treatment of ADHD

• Treatment options for ADHD are often effective (around 70-90% success rate).
• Commonly used treatments include psychostimulant medications like methylphenidate (Ritalin/Concerta), amphetamines (Adderall), and d-amphetamine (Dexedrine).
• These medications increase dopamine levels in the brain.

How Do Treatments Work?

• ADHD medications impact the dopamine system by manipulating dopamine transporter activity.
• This results in enhanced dopamine levels in the synapse.

Prefrontal Cortex (PFC) - D1 Receptor and NA α2A Receptor Stimulation

• Prefrontal cortex requires proper catecholamine levels for optimal function.
• Guided attention and responses occur when the correct levels of catecholamines are present.
• Impulsivity, inattention and difficulty concentrating are linked to under-activation and/or under-stimulation in this brain region.

Ethics of ADHD Treatment

• It is important to have a nuanced discussion regarding treatment and to carefully consider the need for effective parenting and schooling.
• Animal studies suggest the potential long-term side effects of ADHD medication and it is inappropriate to generalize findings to humans.
• ADHD symptoms often improve as the child develops; however this does not negate the potential long-lasting consequences of the disorder and the need for treatment in some cases.