Dexmethylphenidate

Dexmethylphenidate is the more active d-enantiomer of methylphenidate. It is used for attention deficit hyperactivity disorder in children aged 6 years and over and in adults. The dose is about half that of methylphenidate, and the safety profile, controlled-drug status and monitoring requirements are the same.

Classification. Central nervous system stimulant, piperidine derivative.

Mechanism. Blocks reuptake of dopamine and noradrenaline by inhibiting the dopamine and noradrenaline transporters.

Pharmacokinetics. Well absorbed orally, peak in about 1 to 1.5 hours for immediate release (and a second peak about 6 to 7 hours for extended release). Hydrolysed by carboxylesterase 1 to d-ritalinic acid, which is inactive. Half-life about 2 to 4.5 hours. Extended-release capsules act for 8 to 12 hours.

All regimens are oral with no loading dose.

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

• Start 2.5 mg twice daily.
• Titration: increase by 2.5 to 5 mg weekly.
• Maximum 20 mg daily in two divided doses, given at least 4 hours apart.

ADHD (extended-release capsules).

• Children aged 6 years and over: start 5 mg once daily in the morning; increase by 5 mg weekly; maximum 30 mg daily.
• Adults: start 10 mg once daily (or 5 mg if already taking methylphenidate, using half the methylphenidate daily dose); increase by 10 mg weekly; maximum 40 mg daily.
• Switching from methylphenidate: use half the total daily dose.

Dose limits. Review treatment at least yearly and consider a break. Stop if there is no benefit after one month at an adequate dose.

Contraindications. Concurrent monoamine oxidase inhibitor or within 14 days of stopping one, severe hypertension, heart failure, arrhythmia, structural cardiac abnormality, 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, Raynaud phenomenon, growth slowing in children, depression or suicidal thoughts, dependence and misuse.

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. It can raise levels of warfarin and some anticonvulsants. It can reduce the effect of antihypertensives. Alcohol worsens central nervous system effects.

Common prescribing errors. Using a methylphenidate dose without halving it; not naming the formulation; late-day dosing; omitting height, weight and blood pressure records; continuing without yearly review.

Special groups.

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

Formulations. Immediate-release tablets 2.5 mg, 5 mg and 10 mg; extended-release capsules 5 mg to 40 mg. Extended-release capsules can be opened and sprinkled on a spoonful of cool soft food and swallowed without chewing. Give the last dose of immediate release before 4 pm.

Baseline. Blood pressure, pulse, height and weight, cardiovascular history, family history of sudden cardiac death, psychiatric history including tics and substance use, khat and alcohol use.

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

Stopping. No taper is needed; stop with review because mood and attention may worsen.

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