Methylphenidate

Methylphenidate is a central nervous system stimulant used for attention deficit hyperactivity disorder in children aged 6 years and over and in adults, and for narcolepsy. It is a controlled drug with a significant potential for misuse and diversion, so it is prescribed and dispensed under specialist supervision. Immediate-release and several modified-release products differ in duration, and the formulation must be named when prescribing.

Classification. Central nervous system stimulant, piperidine derivative.

Mechanism. Blocks reuptake of dopamine and noradrenaline by inhibiting the dopamine and noradrenaline transporters, which increases synaptic levels in the prefrontal cortex and striatum.

Pharmacokinetics. Well absorbed orally with extensive first-pass metabolism (bioavailability about 30%). Hydrolysed by carboxylesterase 1 to the inactive ritalinic acid, so it is not affected by most cytochrome interactions. Immediate release: peak in 1 to 2 hours, half-life 2 to 3 hours, effect lasts 3 to 5 hours. Modified release lasts 8 to 12 hours depending on the product.

All regimens are oral with no loading dose.

ADHD, children aged 6 years and over (immediate release).

• Start 5 mg once or twice daily (morning and lunchtime).
• Titration: increase by 5 to 10 mg at weekly intervals.
• Usual 20 to 30 mg daily in two or three divided doses. Maximum 60 mg daily.

ADHD, children aged 6 years and over (osmotic-release extended release).

• Start 18 mg once daily in the morning.
• Titration: increase by 9 to 18 mg at weekly intervals.
• Maximum 54 mg daily in children (72 mg in adolescents in some labels).

ADHD, adults.

• Immediate release: start 5 mg two or three times daily; increase weekly by 5 to 10 mg; usual 20 to 60 mg daily in divided doses; maximum 60 mg daily.
• Extended release: start 18 mg once daily in the morning; increase weekly; maximum 72 mg daily.

Narcolepsy, adults (immediate release). 10 mg two or three times daily; titrate to response; usual 20 to 30 mg daily; maximum 60 mg daily.

Dose limits. Treatment is reviewed at least once a year, and a break in treatment is considered to check that the medicine is still needed. Stop if there is no benefit after one month at an adequate dose. Kidney and liver impairment: no formal adjustment, use with caution.

Contraindications. Concurrent monoamine oxidase inhibitor or within 14 days of stopping one, severe hypertension, heart failure, arrhythmia, structural cardiac abnormality, cardiomyopathy, hyperthyroidism, phaeochromocytoma, glaucoma, severe depression, suicidal ideation, psychosis or mania, undiagnosed tics. Major warning of abuse, misuse and addiction.

Serious adverse effects. Hypertension, tachycardia and arrhythmias, sudden death with structural heart disease, psychosis or mania, seizures, priapism, peripheral vasculopathy (Raynaud phenomenon), growth slowing in children, depression or suicidal thoughts, dependence and misuse, worsening tics.

Common adverse effects. Reduced appetite, weight loss, insomnia, headache, abdominal pain, nervousness, irritability, tachycardia.

Interactions. Monoamine oxidase inhibitors are contraindicated. Other sympathomimetics and khat (cathinone) add cardiovascular and psychiatric effects, so ask about khat chewing. Methylphenidate can raise levels of warfarin, phenytoin, phenobarbital, primidone and tricyclic antidepressants. It can reduce the effect of antihypertensives. Alcohol worsens central nervous system effects. Clonidine with methylphenidate has been associated with rare serious events, so the combination needs specialist care.

Common prescribing errors. Prescribing without a cardiovascular history and blood pressure; giving a modified-release product without naming it; late-day dosing causing insomnia; not recording height and weight in children; continuing without review; dispensing large supplies to patients at risk of diversion.

Special groups.

• Pregnancy: avoid unless the benefit clearly outweighs the risk; data on fetal risk are limited.
• Breastfeeding: small amounts in milk; avoid or monitor the infant.
• Children: not for children under 6 years; monitor growth.
• Older adults: limited data; use with caution.
• Kidney impairment: no formal adjustment.
• Liver impairment: use with caution.

Formulations. Immediate-release tablets 5 mg, 10 mg and 20 mg; osmotic-release extended-release tablets 18 mg, 27 mg, 36 mg and 54 mg; modified-release capsules 10 mg, 20 mg, 30 mg and 40 mg; transdermal patch in some regions. Swallow extended-release tablets whole. Give the last dose of immediate release before 4 pm.

Baseline. Blood pressure, pulse, height and weight (plotted in children), cardiovascular history and family history of sudden cardiac death, examination of the heart, psychiatric history including tics and substance use, khat and alcohol use. Obtain an ECG if there is a cardiac history, family history, or abnormal examination.

Monitoring. Check blood pressure, pulse and weight every 3 to 6 months, and height every 6 months in children. Review the need for treatment at least yearly. Ask about appetite, sleep, mood, tics and misuse.

Stopping. No taper is needed, but stop with review because mood and attention may worsen. Withdrawal after prolonged high-dose use can cause depression and fatigue.

Referral and escalation. Refer to a specialist for diagnosis and initiation, for psychiatric or cardiac complications, and for suspected misuse. Chest pain, syncope, psychosis or priapism needs urgent assessment.