methylphenidate (MPH) has been shown to act as a norepinephrine and dopamine reuptake inhibitor (NDRI), thereby increasing the presence of these neurotransmitters in the extraneuronal space and prolonging their action. There is a dose-related effect of psychostimulants on receptor stimulation, where higher doses are shown to increase norepinephrine (NE) and dopamine (DA) efflux throughout the brain which can result in impaired cognition and locomotor-activating effects. In contrast, low doses are found to selectively activate NE and DE neurotransmission within the prefrontal cortex which is an area of the brain thought to play a prominent role in ADHD pathophysiology, thereby improving clinical efficacy and preventing side effects. The lower doses used to treat ADHD are not associated with the locomotor-activating effects associated with higher doses and instead reduce movement, impulsivity, and increase cognitive function including sustained attention and working memory. Methylphenidate's beneficial effects in sustaining attention have also been shown to be mediated by alpha-1 adrenergic receptor activity.

Clinical findings have shown that children with ADHD have an abnormality in the dopamine transporter gene (DAT1), the D4 receptor gene (DRD-4), and/or the D2 receptor gene that may be at least partly overcome by the dopaminergic effects of methylphenidate, suggesting a possible mode of action.

Methylphenidate is used in the treatment of attention deficit hyper activity disorder (ADHD) and narcolepsy.

Child: Over 6 years, initially 5 mg 1-2 times daily, increased if necessary at weekly intervals by 5-10 mg daily to max. 60 mg daily in divided doses; discontinue if no response after one month also suspend periodically to assess child’s condition (usually finally discontinued during or after puberty); Child under 6 years not recommended.

Adult: 10-15 mg daily in divided doses (2-3 times daily). Average dosage is 20-30 mg daily. Some patients may require 40-60 mg daily. Patients who are unable to sleep if medication is taken late in the day should take the last dose before 6 pm.

Administration

Should be taken on an empty stomach. Take 30-45 min before meals. May be taken with or without food.  Swallow whole, do not divide/chew/crush.

Methylphenidate is contraindicated in alcoholics, emotionally unstable patients, drug abusers, hypertension, cardiac arrhythmias, psychoses, epilepsy, thyro-toxicosis, glaucoma marked anxiety, severe depression and known sensitivity to methylphenidate.

Sleep disturbances, restlessness, dizziness, headache, tremor, convulsion, rash, pruritis; urticaria, fever, arthralgia, alopecia, exfoliative, dermatitis, erythema multiforme, thrombocytopenic purpuria, thrombocytopenia, Leucopenia, urinary disorder and very rarely liver damage.

In mild hypertension (contraindicated if moderate or severe)-monitor blood pressure; history of epilepsy; tics and Tourette syndrome. Occasional cystic ovarian swellings in premenopausal women, occasional hypercalcemia if bony metastases; increased risk of thromboembolic events when used with cytotoxics; breast feeding; endometrial changes; porphyria

Pregnancy & Lactation

The use of methylphenidate in pregnancy and lactation has not been established.