Methylphenidate

Methylphenidate, short: MPH; is a drug with the molecular formula: C14H19NO2. The average half-life is about 2.0 h. Like amphetamine, methamphetamine or tyramine, methylphenidate belongs to the group of indirectly acting sympathomimetics.

Note: Methylphenidate was discovered in 1944 by the Swiss chemist Leandro Panizzon. In the Federal Republic of Germany the drug is classified as a narcotic and is subject to a special prescription.

Methylphenidate acts as an indirect sympathomimetic by releasing noradrenaline from intraneuronal stores of adrenergic neurons and inhibiting reuptake indirectly sympathomimetically (see figure). With increasing concentration in the central nervous system, methylphenidate also releases dopamine and inhibits its reuptake. The central stimulating effect manifests itself, among other things, in an increase in the ability to concentrate, performance and decision-making, suppression of fatigue and physical exhaustion.

Pharmaokinetics: Methylphenidate is rapidly and almost completely absorbed. The relatively short half-life (2 h) correlates well with the duration of action of 1 to 4 hours. Methylphenidate is rapidly and almost completely metabolized by the carboxylesterase CES1A1 and mainly degraded to ritalic acid with low pharmacodynamic activity. After oral administration, 78-97% of the dose is excreted in urine and 1 to 3% in faeces in the form of metabolites within 48 to 96 hours.

Treatment of ADHD in children and adolescents (6 years and >6 years): Treatment should be started with 5 mg once or twice a day (e.g. in the morning and at noon) of short-acting or rapidly releasing methylphenidate. If necessary, the daily dose can be increased by 5-10 mg at weekly intervals. The maximum daily dose of 60 mg should not be exceeded. The total daily dose should be divided into 2 - 3 individual doses.

ADHD in adults: Initial dose: 10 mg/day. If necessary, the daily dose can be increased weekly in steps of 10 mg daily. The total daily dose should be divided into 2ED (morning and noon). Maximum daily dose 1 mg/kg bw. The maximum daily dose of 80 mg methylphenidate hydrochloride should not be exceeded in adults.

Narcolepsy in children and adolescents (6 years and > 6 years): Treatment should be started with 5 mg once or twice a day (e.g. morning and noon) of short-acting or rapidly releasing methylphenidate. If necessary, the daily dose can be increased by 5-10 mg at weekly intervals. The maximum daily dose of 60 mg should be observed.

Treatment of adults with narcolepsy: The average daily dose is 20 - 30 mg and should be divided into 2 - 3 single doses. The maximum daily dose of 80 mg should be observed.

Note: Frequencies: ADR's are classified according to their frequency in:

• very often >1:10
• frequent (> 1:100 <1:10)
• occasionally (>1:1,000<1:100)
• rare (>1:10,000 <1:1,000)
• very rare (<1:10,000 including individual reports).

Among the very common (≥ 1/10) side effects are: loss of appetite, insomnia, nervousness, lack of concentration and sensitivity to noise (in adults with narcolepsy), headache, nausea, dry mouth, sweating

The most common side effects (≥ 1/100 to < 1/10) include: Anorexia, moderate reduction in weight gain and length growth with prolonged use in children, abnormal behavior, aggression, affect lability, agitation, anorexia, anxiety, depression, irritability, restlessness, insomnia, Decrease in libido, panic attacks, dyskinesia, tachycardia, palpitations, arrhythmias, hypertension, peripheral sensation of cold (these symptoms usually occur at the beginning of treatment and can be alleviated by accompanying food intake)

Glaucoma, pheochromocytoma. During treatment with non-selective, irreversible monoamine oxidase (MAO) inhibitors or within at least 14 days after stopping such substances, as there is then a risk of hypertensive crisis. Hyperthyroidism or thyrotoxicosis

Limited choice: Ritalin®, Medikinet®, Concerta®

Treatment with drugs is carried out according to guidelines and within the framework of a multimodal therapy concept. It is not suitable for monotherapy. The individual benefit and effectiveness of methylphenidate on ADHD symptoms can vary considerably and depends on a number of factors. In cases of severe symptoms, enormous improvements can sometimes be achieved with drug combination treatment.

1. Fekete S et al (2017) Does methylphenidate induce liver damage? - Analysis of spontaneous reports to the Federal Institute for Drugs and Medical Devices (BfArM). Z Children Adolescent psychiatrist Psychother 46:342-348.
2. Graefe KH et al. (2016) Sympathetic Nervous System. In: Graefe KH et al. pharmacology and toxicology. Georg Thieme Publishing House, Stuttgart S.96
3. Gautschi OP et al. (2006) Necrotising myositis after intravenous methylphenidate (Ritalin) injection. Emerg Med J 23:739.
4. Gehrmann J et al. (2017) Narcolepsy in childhood and adolescence: symptoms, diagnosis and therapy. A case report. Z Children Adolescent Psychiatrist Psychother 45:149-157.