ADHD Pharmacology

Cheatsheet Content

### ADHD Overview Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by persistent patterns of inattention, hyperactivity, and/or impulsivity that interfere with functioning or development. #### Diagnostic Criteria (DSM-5) - **Inattention:** ≥6 symptoms (≥5 for adults/adolescents) for at least 6 months. - **Hyperactivity & Impulsivity:** ≥6 symptoms (≥5 for adults/adolescents) for at least 6 months. - Symptoms present before age 12. - Symptoms present in ≥2 settings (e.g., school, home, work). - Symptoms interfere with social, academic, or occupational functioning. - Not better explained by another mental disorder. #### Neurobiology - Primarily involves dysfunction in dopamine and norepinephrine pathways in the prefrontal cortex. - Leads to impaired executive functions (e.g., planning, working memory, impulse control). ### Treatment Principles - **Multimodal Approach:** Often combines pharmacotherapy with behavioral therapy, psychoeducation, and lifestyle modifications. - **Individualized Treatment:** Medication choice, dosage, and schedule are tailored to the individual's age, symptom profile, comorbidities, and response/tolerability. - **Titration:** Start low and go slow to find the optimal therapeutic dose with minimal side effects. - **Monitoring:** Regular assessment of efficacy, side effects, growth, and cardiovascular parameters. ### Stimulants (First-Line) Increase dopamine and norepinephrine in the synaptic cleft, primarily in the prefrontal cortex. #### 1. Methylphenidate (MPH) - **Mechanism:** Primarily blocks dopamine and norepinephrine reuptake. - **Forms:** - **Short-Acting (SA):** Ritalin, Methylin (onset ~30 min, duration 3-5 hrs). - **Intermediate-Acting (IA):** Ritalin SR, Metadate ER (onset ~30-60 min, duration 4-8 hrs). - **Long-Acting (LA):** Concerta, Ritalin LA, Focalin XR, Quillivant XR, Adhansia XR, Jornay PM (onset ~30-60 min, duration 8-16 hrs). - **Transdermal:** Daytrana patch (onset ~1-2 hrs, duration ~12 hrs after patch removal). - **Chewable/Liquid:** Quillichew ER, Quillivant XR. #### 2. Amphetamines (AMP) - **Mechanism:** Blocks reuptake and increases release of dopamine and norepinephrine. - **Forms:** - **Short-Acting (SA):** Dextroamphetamine (Dexedrine, Zenzedi), Mixed Amphetamine Salts (Adderall) (onset ~30 min, duration 4-6 hrs). - **Long-Acting (LA):** Adderall XR, Vyvanse, Dexedrine Spansule, Adzenys XR-ODT, Dyanavel XR, Mydayis (onset ~30-60 min, duration 10-14 hrs). - **Prodrug:** Lisdexamfetamine (Vyvanse) is converted to dextroamphetamine in the GI tract, leading to a smoother release profile and lower abuse potential. #### Common Side Effects (Stimulants) - **Cardiovascular:** Increased heart rate, blood pressure (monitor regularly). - **Psychiatric:** Anxiety, irritability, insomnia (dose-dependent), rare psychosis/mania. - **Gastrointestinal:** Decreased appetite, stomach ache, nausea. - **Neurological:** Headache, tics (can exacerbate pre-existing tics). - **Growth:** Potential for mild growth suppression in children (monitor height/weight). #### Contraindications/Precautions - Symptomatic cardiovascular disease, moderate-to-severe hypertension. - Hyperthyroidism. - Glaucoma. - History of severe anxiety, psychosis, or substance abuse. - Concomitant use with MAOIs (risk of hypertensive crisis). ### Non-Stimulants (Second-Line) Used when stimulants are ineffective, not tolerated, or contraindicated. #### 1. Atomoxetine (Strattera) - **Mechanism:** Selective norepinephrine reuptake inhibitor (SNRI). - **Onset of Action:** Slower (2-4 weeks for full effect). - **Advantages:** 24-hour symptom control, not a controlled substance, lower abuse potential. - **Side Effects:** Nausea, vomiting, fatigue, decreased appetite, dry mouth, insomnia, increased heart rate/BP. - **Black Box Warning:** Increased risk of suicidal ideation in children/adolescents. - **Drug Interactions:** CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) can increase atomoxetine levels. #### 2. Guanfacine Extended-Release (Intuniv) / Clonidine Extended-Release (Kapvay) - **Mechanism:** Alpha-2 adrenergic agonists. Primarily target the prefrontal cortex to improve attention, impulsivity, and reduce hyperactivity. - **Onset of Action:** Slower (weeks for full effect). - **Advantages:** Can improve sleep, reduce tics, and manage aggression. Often used as adjunctive therapy with stimulants. - **Side Effects:** Sedation, fatigue, dizziness, hypotension, bradycardia, dry mouth. - **Precautions:** Do not discontinue abruptly due to risk of rebound hypertension. #### 3. Bupropion (Wellbutrin) - **Mechanism:** Norepinephrine-dopamine reuptake inhibitor (NDRI). - **Use:** Off-label for ADHD, especially with comorbid depression or nicotine dependence. - **Side Effects:** Insomnia, dry mouth, nausea, headache, tremor. - **Contraindications:** Seizure disorder, eating disorders (increased seizure risk). ### Adjunctive Therapies Used to manage specific symptoms or comorbidities when primary treatments are insufficient. #### 1. Antidepressants - **SSRIs/SNRIs:** For comorbid anxiety or depression (e.g., fluoxetine, sertraline, venlafaxine). - **TCAs (e.g., Imipramine, Desipramine):** Historically used, but less common due to side effects (cardiac, anticholinergic). #### 2. Antipsychotics (Atypical) - **Low Dose:** For severe aggression or disruptive behaviors not responsive to other treatments (e.g., risperidone, aripiprazole). - **Side Effects:** Metabolic changes (weight gain, dyslipidemia), sedation, extrapyramidal symptoms. #### 3. Other - **Melatonin:** For stimulant-induced insomnia. - **Cognitive Behavioral Therapy (CBT):** For executive function deficits, emotional dysregulation, and comorbid anxiety/depression. - **Parent Training/Behavioral Therapy:** Essential for children and adolescents. ### Monitoring & Follow-Up - **Baseline Assessment:** - Comprehensive history (medical, psychiatric, family). - Physical exam, vital signs (HR, BP), height, weight. - ECG (if clinically indicated by history/exam, not routine for all). - **During Treatment:** - **Efficacy:** Symptom rating scales (e.g., ADHD-RS, Vanderbilt), input from parents/teachers/patient. - **Side Effects:** Regular inquiry about appetite, sleep, mood, GI issues. - **Growth:** Plot height and weight on growth charts (especially for children). - **Cardiovascular:** Monitor HR and BP at each visit, consider repeat ECG if new symptoms or concerns arise. - **Frequency:** - Initial titration: Weekly or bi-weekly. - Stable dose: Every 3-6 months, or as clinically indicated. ### Special Considerations #### Comorbidity Management - **Anxiety/Depression:** Treat concurrently. Stimulants can sometimes exacerbate anxiety, atomoxetine or bupropion may be better initial choices. - **Oppositional Defiant Disorder (ODD)/Conduct Disorder (CD):** Stimulants can help reduce aggression and impulsivity. Alpha-2 agonists may also be beneficial. - **Substance Use Disorder (SUD):** Non-stimulants (atomoxetine, guanfacine) are preferred. If stimulants are used, extended-release formulations like Vyvanse may be safer. - **Tic Disorders:** Stimulants can sometimes worsen tics. Atomoxetine, guanfacine, or clonidine are preferred. #### Pregnancy & Lactation - Generally, medications should be avoided or used with caution. - Risk-benefit discussion is crucial. - Non-pharmacological interventions are first-line. #### Geriatric Population - Start with lower doses and titrate slowly due to increased sensitivity and potential for comorbidities/polypharmacy. - Monitor closely for cardiovascular side effects and drug interactions. #### Drug Holidays - Historically common, but less routinely recommended now. - Can be considered for appetite suppression or to assess ongoing need for medication. - May lead to symptom rebound and difficulties with school/work performance.