Understanding ADHD: Symptoms, Diagnosis, and Subtypes

Overview of ADHD

• ADHD is the most common childhood psychiatric condition
• Symptoms include inattention, impulsivity, and/or hyperactivity
• Onset typically occurs by age 3, but must occur by age 12
• Diagnosis must be confirmed, as ADHD symptoms can indicate other psychiatric disorders

Diagnosis (DSM-5 Criteria)

• Inattention involves failure to pay close attention, difficulty sustaining attention, easy distractibility, and forgetfulness
• Hyperactivity/impulsivity includes fidgeting, inability to stay seated, excessive talking, impatience, and interrupting others
• ADHD Subtypes include Predominantly Inattentive, Predominantly Hyperactive-Impulsive and Combined Type
• Impaired function must occur in multiple settings (home, school, work)
• Symptoms interfere with or reduce the quality of social, academic, or occupational functioning
• Most patients do not "grow out of" ADHD
• As patients age, the hyperactive/impulsive subtype diminishes, and inattentive becomes more common
• Evaluate children/adolescents aged 4-18 years and obtain reports on the child's symptoms from parents/guardians, school staff, and mental health workers

ADHD Tools for Diagnosis

• NICHQ Vanderbilt Assessment Scale is used for teachers/parents
• Conners' Adult ADHD Rating Scales, particularly the Conners' Abbreviated Symptom Questionnaire, is a brevity and diagnostic accuracy tool
• Child Behavior Checklist (CBCL) is recommended for comprehensive assessments
• Computerized Tests of Attention are available

ADHD Epidemiology & Risk Factors

• More common in boys, with a 2-4:1 ratio in children
• Prevalence is equal in adults
• Higher prevalence in Non-Hispanic Caucasian and Black children
• Risk factors include genetic predisposition, prenatal tobacco/alcohol exposure, obstetric adversity, adverse parent/child relationships, environmental toxins (lead, pesticides), and nutritional deficiencies (iron, zinc, copper, magnesium, B6, fatty acids)

ADHD Pathophysiology

• Brain Structure and Function: Decreased volume in the prefrontal cortex, caudate nucleus, anterior cingulate gyrus, and cerebellum
• Dysfunction occurs in dopamine (D4 receptor) and norepinephrine pathways
• Functional MRI Findings: Reduced activation in attention and impulse control areas
• Default mode network (DMN) connectivity issues cause lapses in attention

ADHD Comorbid Conditions

• Comorbid conditions include learning disabilities, conduct disorder & oppositional defiant disorder, mood disorders (depression, bipolar disorder), anxiety disorder, substance abuse, Tourette’s syndrome, and autism spectrum disorder

Goals of Therapy

• Goals include improvement in overall functioning, baseline rating scales, relationships, academic performance, and self-esteem
• Therapy aims to decrease motor activity and impulsivity as well as disruptive behavior

Non-Pharmacologic Treatment

• Behavioral Interventions include parent training, classroom management, behavioral peer interventions, token economy, positive reinforcement, and time-out strategies, and cognitive-behavioral therapy for adolescents & adults
• Educational Support includes Individualized Education Programs (IEP) and 504 Plans

Pharmacologic Treatment

• Stronger effect on ADHD core symptoms than behavior therapy alone
• Combining behavior therapy and medication produces positive effects, and behavioral interventions may allow for effective lower stimulant doses

Stimulants (First-Line Treatment)

• All stimulants are C-II drugs
• All stimulants are equally effective
• Alternate therapy should be considered if co-morbidities are present
• All stimulants are approved for children, adolescents, and adults
• Do not start stimulants within 14 days of discontinuing a MAOI
• If the first stimulant formulation fails, switching to a different stimulant class is advised

Methylphenidate

• Ritalin, Concerta, Daytrana (Patch), Metadate, Aptensio XR, Quillivant XR, Quillichew ER, Cotempla XR
• Short-acting: Ritalin chewable tablets, liquid
• Intermediate-acting: Metadate tablets
• Long-acting: Aptensio XR (capsule), Concerta (tablet will appear in stool), Quillivant (oral suspension), Daytrana transdermal patch to wear for only 9 hours, onset 2 hours
• May be preferred if misuse and diversion are a concern and a stimulant is necessary
• It has less adverse effects compared to amphetamines, and fewer DDIs compared to MAS
• Preferred initial stimulant in children AND initial stimulant in patients with ASD and if the patient also has Tourette's syndrome

Dexmethylphenidate

• Focalin, Focalin XR
• Capsules can be opened and poured into liquid or applesauce
• More potent and longer-lasting than Methylphenidate

Serdexmethylphenidate/dexmethylphenidate:

• Azstarys
• Long-acting
• For patients with ADHD 6 years and older
• Swallow capsules whole or open and sprinkle onto applesauce

Mixed Amphetamine Salts:

• Adderall, Adderall XR, Mydayis
• Mydayis has the longest duration of action at 16 hours
• Amphetamines, especially MAS, are metabolized by the CYP2D6 enzyme
• Watch for Polymorphisms and DDIs, Antidepressants and Antipsychotics

Amphetamine sulfate:

• Evekeo
• Short-acting

Lisdexamfetamine:

• Vyvanse is long acting
• A prodrug converted to Dextroamphetamine
• Preferred if diversion is a concern, as it cannot be snorted

Amphetamine

• Adzenys XR-ODT/ER oral suspension, Dyanavel XR

Dextroamphetamine:

• Xelstrym Transdermal System is for ADHD & Narcolepsy in adults/children 6 years and older
• It inhibits dopamine/norepinephrine reuptake and increases catecholamine levels
• Alternative therapy is to be considered in anxiety, depression, bipolar disorder, or substance abuse history

Non-Stimulants (Second-Line or Adjunctive)

• Atomoxetine (Strattera) is a norepinephrine reuptake inhibitor
• It takes time to see improvements in ADHD symptoms
• Unlike stimulants, it has no abuse potential and is not a controlled substance
• It is may be a preferred treatment in co-morbid conditions of anxiety, active substance abuse, or family members with stimulant SUD
• Onset of action is 2-4 weeks
• BBW: Suicidal ideation in children and adolescents and warning for severe liver injury and CV events
• It is metabolized by CYP2D6 so watch for DDI with fluoxetine

Viloxazine (Qelbree)

• Similar to atomoxetine and is newly approved
• For treatment of ADHD in patients aged 6-17 years and approved for adults as well
• Screen patients for a history of suicide, bipolar disorder, and depression before starting
• Use a lower dose for renal impairment (eGFR less than 30)
• Avoid concomitant use with MAOI or within 14 days of MAOI discontinuation because of increased risk of hypertensive crisis and BBW for suicidal thoughts and behaviors
• Check Assess HR and BP

Bupropion (Wellbutrin):

• Dopamine & norepinephrine reuptake inhibitor
• 2nd line and not FDA approved for ADHD
• Contraindicated in seizure and eating disorders

Clonidine/Guanfacine (Alpha-2 Agonists):

• Used adjunctively for impulsivity, aggression, or tics
• Does not help with inattentive ADHD
• Requires tapering to avoid rebound HTN
• Especially effective for ADHD with aggressiveness, disruptive behavior, and insomnia or comorbid tic disorder
• Clonidine (Catapres IR and Patch & Kapvay ER taken twice daily): AE: Hypotension, bradycardia, QT prolongation
• Guanfacine (Tenex IR & Intuniv ER)

Mood Stabilizers

• Lithium and Anticonvulsants like Valproate, Oxcarbazepine, and Carbamazepine
• Not effective for inattentive subtype
• For patients who have Bipolar disorder & ADHD, the patient must be on a mood stabilizer before initiating stimulant

Antipsychotics

• Second-generation (atypical) are preferred in children - especially Risperidone, Aripiprazole, Haloperidol, Olanzapine, Quetiapine, Ziprasisone, or Lurasidone
• Can cause extrapyramidal symptoms

Stimulant Adverse Effects & Management

• Common: Insomnia, so give dose earlier in the day or consider a sedating medication at bedtime such as cyproheptadine
• Appetite suppression/weight loss, so give high-calorie meals when stimulant effects are low such as breakfast, dinner, or at bedtime or try cyproheptadine to stimulate appetite, headache, and irritability
• Rare/Serious: Increased heart rate, blood pressure, psychiatric symptoms (psychosis, mania, aggression Reduce dose or stop stimulant therapy) and skin discoloration with the methylphenidate patch
• Growth Effects: Small height deficit (~1 cm/year in early treatment)
• Consider drug-free weekends and a drug-free trial every year during summer to assess the necessity of medication
• Cardiovascular Risk: Increased risk of hypertension and arrhythmias, so baseline ECG recommended if risk factors are present.
• Clonidine and Guanfacine may cause dose-related bradycardia and lowered BP in youth and may prevent upward titration in addition to modest widening of the QTc interval that warrants monitoring.
• CV events were rate but TWICE AS LIKELY in stimulant users as in non-users
• Stimulant products should be used with caution in pediatrics and adults with known structural cardiac abnormalities
• Get screening of all children and adolescents prior to initiating pharmacological therapy for ADHD, including a medical and family history and physical exam.

ADHD and Substance Use Risk

• ADHD is an independent risk factor for substance use disorder (SUD)
• Early treatment with stimulants may have a protective effect against SUD
• High risk of stimulant misuse; non-stimulants may be preferable in at-risk populations

ADHD Treatment Guidelines (AAP, 2011 & 2019)

• Preschool (4-5 YOA): Behavioral therapy first-line, methylphenidate if necessary for moderate-severe disturbance
• Children (6-11 YOA): Stimulants and/or behavioral therapy, preferably both
• Adolescents (12-18 YOA): Stimulants with adolescent assent, behavioral therapy as adjunct, preferably both
• Adults: No official guidelines yet; treatment decisions based on childhood history
• Emphasize ruling out other causes of ADHD-like symptoms and identifying comorbid conditions

Special Populations & Considerations

• ADHD & Autism: Stimulants are less effective; Clonidine/Guanfacine helps and Methylphenidate is an option
• ADHD & Anxiety: Stimulants should improve anxiety; if worsened, consider Atomoxetine
• ADHD & Bipolar: Mood stabilizers are required before stimulant initiation
• ADHD & Aggression: High-dose stimulants, Alpha-2 agonists, mood stabilizers, and atypical antipsychotics

ADHD Medication Guide & Black Box Warnings

• High abuse potential of stimulants; monitor for dependence with misuse of amphetamines and CV events with adderall.
• Medication Guide Includes: Pharmacy MUST include a medication guide when dispensing a stimulant, including heart-related risks (sudden death, stroke, heart attack, hypertension) and psychiatric risks (aggression, mood disturbances, psychosis)

Complementary & Alternative Treatments

• Dietary Interventions: Allergy elimination, Feingold diet.
• Nutritional Supplements: Iron, zinc, magnesium, omega-3 fatty acids.
• Botanicals: Bacopa monnieri, Ginkgo biloba, Panax ginseng.