Methylphenidate
Methylphenidate
Generic Name
Methylphenidate
Mechanism
- Presynaptic dopamine (DA) and norepinephrine (NE) reuptake inhibitor
- MPH blocks dopamine transporter (DAT) and norepinephrine transporter (NET) more potently in the prefrontal cortex.
- Increased synaptic DA/NE
- Enhances cognitive focus, impulse control, and executive function.
- Metabolism to r‑methylphenidate (74 % of activity) provides a longer half‑life in some ER products.
- Minimal direct receptor agonism; no significant interaction with adrenergic or dopaminergic receptors.
Pharmacokinetics
| Parameter | Typical IR | Typical ER |
| Absorption | Rapid, peak in 30–60 min | Peak 4–6 h (modified-release) |
| Bioavailability | 30–80 % | ~50 % |
| Distribution | Vd 0.5 L/kg; mostly protein bound (~35 %) | Similar distribution |
| Metabolism | Primarily CYP2D6‑mediated, epimerization to r‑MPH | Engineered for slower release; slower metabolism |
| Half‑life | 1–2 h (IR) | 2–4 h (ER; sustained up to 12 h with some preparations) |
| Excretion | Renal (~75 %) | Renal; unchanged drug and metabolites |
| Drug interactions | Strong MAOIs ↑ plasma levels >400 % | Same caution; ER products less prone to acute toxicity |
Indications
- Attention‑Deficit/Hyperactivity Disorder (ADHD) – children, adolescents, adults.
- Narcolepsy – for excessive daytime sleepiness (often part of dual‑therapy regimens).
- Off‑label uses (judgment‑based by prescriber):
- Mild cognitive deficits post-mild brain injury.
- Sluggish processing in elderly patients with transient ischemic attacks (TIA) – rarely.
Contraindications
- Absolute contraindications
- Known hypersensitivity to MPH or any component.
- Severe cardiovascular disease: uncontrolled hypertension, tachyarrhythmias, structural heart disease.
- Pheochromocytoma.
- Severe anxiety or agitation that may worsen.
- Relative contraindications
- Psychiatric disorders with latent psychosis/aggressive tendencies.
- Recent myocardial infarction.
- Therapy with monoamine oxidase inhibitors (MAO‑I) – avoid or delay at least 14 days after discontinuation.
- Warnings
- Potential for abuse, dependence, and withdrawal.
- May precipitate hypertension/hyperactivity in untreated or undertreated hypertension.
- Use caution in patients with glaucoma (risk of intra‑ocular pressure rise).
- Reports of sudden death in patients with structural cardiac abnormalities.
Dosing
| Age/Weight | Starting Dose | Titration | Maximum Dose (Daily) |
| Children (6–12 yr) | 0.3 mg/kg (max 18 mg) | Increase 2–4 mg weekly | 36 mg |
| Adolescents (≥13 yr) | 5 mg (IR) | Increase 5 mg every 3–5 days | 90 mg |
| Adults | 10 mg (IR) | Increase 10 mg weekly | 60 mg |
| Narcolepsy (all ages) | 0.5 mg/kg (max 60 mg/day) | Increase 2 mg every 3–5 days | 60 mg |
• Immediate‑Release: 1–3 times daily; take with or without food.
• Extended‑Release: Once daily, morning or early afternoon; avoid late timing to reduce nighttime insomnia.
• Adjust for renal/hepatic: Only mild dose reduction needed; no formal adjustment guidelines for mild CKD.
• Tapering: To avoid abrupt withdrawal or rebound insomnia, taper over 1–2 weeks if discontinuation is required.
Adverse Effects
Common (≥5 %)
• Insomnia, sleep disturbances
• Decreased appetite, weight loss (particularly in children)
• Headache, nausea, abdominal discomfort
• Palpitations, increased heart rate (Tachycardia)
• Anxiety, jitteriness
Serious (≤1 %)
• Hypertensive crisis, sudden cardiac death (rare in structurally normal hearts)
• Severe anxiety, panic attacks, or suicidality (especially in adolescents)
• Psychosis, hallucinations, mania (especially with high doses or misuse)
• Severe growth retardation in children (long‑term effect)
• Severe rashes/ hypersensitivity reactions (rare)
Monitoring
- Vitals: BP & HR at baseline, then every 2–4 weeks; more frequent if hypertension develops.
- Growth: Height and weight of children every 3–6 months.
- Psychiatric: Mood, behavior, sleep patterns; screen for suicidality (regular intervals).
- Drug screening: For abuse risk (especially in high‑risk populations).
- Laboratory: Routine labs only if clinically indicated (renal/hepatic panels).
- Cardiac: ECG at baseline in patients with cardiovascular risk factors; repeat if symptoms.
Clinical Pearls
1. “Switch‑to‑methamphetamine” caution: MPH is chemically different from amphetamines; however, abuse profiles overlap. Use caution with mixed stimulant therapies.
2. Delayed‑release formulations lessen dosing frequency but increase the risk of peak‑duration side effects (e.g., insomnia). Use ER only in patients who have titrated successfully with IR and tolerate the peak.
3. Early dosing adjustments: A 2–4 mg incremental increase every 3–5 days is usually adequate; larger jumps can lead to adverse psychiatric events.
4. Growth monitoring: Report any noticeable height stunting early; consider dose reduction or treatment interruption if growth velocity <90 % of expected.
5. CO₂ and stimulant paradox: Some patients exhibit paradoxical calmness when administered IR MPH; careful observation is needed in the first dose.
6. Sleep‑wake circadian considerations: Administer at least 4 h before bedtime; consider "wake‑sleep switch" if daytime insomnia is a primary concern.
7. Co‑administration with antidepressants: SSRIs may increase MPH toxicity; monitor for increased hypertension and neuropsychiatric excitation.
8. Use of BP‑monitor: For patients exhibiting tachycardia or hypertension, home BP monitoring can detect early trends and avoid hospitalization.
9. Intake with food: Decreases the peak concentration for IR but may reduce the overall bioavailability by about 10 %. This can be advantageous in children with severe anorexia or GI disturbances.
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• Reference‑friendly format: This card pulls together the essential data for use by medical students, residents, and practicing clinicians. For in‑depth evidence, consult the latest FDA prescribing information and peer‑reviewed pharmacology texts.