Methylphenidate dosing

Atomoxetine is the most recent addition to the ADHD armamentarium in both children and adults. In clinical studies, atomoxetine has demonstrated superior efficacy over placebo and equivalent efficacy when compared with a suboptimal immediate-release methylphenidate dose.17 20 However, it is not clear whether atomoxetine is superior to typical methylphenidate doses or other stimulant formulations. Atomoxetine may be used as a second- or third-line medication for ADHD. 

Switching from immediate-release methylphenidate Start Focalin at 50% of the methylphenidate dose (administer Focalin in divided bid doses) titrate as above. Maximum total daily dose 10 mg bid... 

Methylphenidate Ritalin-SR Ritalin LA Metadate ER Metadate CD Concerta Slowly absorbed tablet Capsule with 50% methylphenidate dose as immediate-release beads and 50% as delayed-release beads Slowly absorbed tablet with methylphenidate incorporated in a wax matrix tablet, allowing gradual diffusion Capsule that provides 30% of methylphenidate dose hy immediate-release beads and 70% of the dose by extended-release beads Tablet that contains approximately 22% of the methylphenidate dose in an immediate-release capsule overcoat and 78% within the tablet that is released by an osmotic process over an extended period... 

Ritalin LA, which contains half the methylphenidate dose in immediate-release heads and half the dose in enteric-coated, delayed-release heads, is also intended to provide efficacy throughout at least the school day (Biederman et al. 2003 Lopez et al. 2003). 

As with other stimulants, chorea (24) and choreoathe-tosis (25) can be precipitated in children and adults at methylphenidate doses ranging from therapeutic to abuse... 

GreenhUl LL, Swanson JM, Vitiello B, Davies M, Qevenger W, Wu M, Arnold LE, Abikoff HB, Bukstein OG, Conners CK, Elliott GR, Hechtman L, Hinshaw SP, Hoza B, Jensen PS, Kraemer HC, March JS, Newcom JH, Severe JB, Wells K, Wigal T. Impairment and deportment responses to different methylphenidate doses in children with ADHD the MTA titration trial. J Am Acad Child Adolesc Psychiatry 2001 40(2) 180-7. 

A 6-year-old girl with ADHD and pervasive developmental disorder and behavioural problems who was treated with Depakote (valproic acid) and had an abnormal electrocardiogram (ECG) with left Centro parietal spikes experienced a convulsion the day after the first administration of a methylphenidate dose. A repeat electroencephalography demonstrated continuous spike and slow wave during sleep [73 ]. 

Dopaminergic mechanisms within the ventral striatum (i.e., nucleus accumbens) subserve the ability of amphetamine and methylphenidate in low to moderate doses to increase locomotor activity. In contrast, very low dosages in animals seem to cause hypoactivity presumably by stimulation of autoreceptors, a finding that would be compatible with the clinical impression that methylphenidate might be usefiil in some patients with mania. 

At low doses, both psychostimulants could theoretically stimulate tonic, extracellular levels of monoamines, and the small increase in steady state levels would produce feedback inhibition of further release by stimulating presynaptic autoreceptors. While this mechanism is clearly an important one for the normal regulation of monoamine neurotransmission, there is no direct evidence to support the notion that the doses used clinically to treat ADHD are low enough to have primarily presynaptic effects. However, alterations in phasic dopamine release could produce net reductions in dopamine release under putatively altered tonic dopaminergic conditions that might occur in ADHD and that might explain the beneficial effects of methylphenidate in ADHD. 

The development of psychosis is the most striking clinical characteristic of high-dose stimulant abuse. The amphetamines, methylphenidate, and phen-metrazine all produce psychosis (Ellinwood et al. 1973 Harris and Batki 2000 Iversen et al. 1978 Lucas and Weiss 1971 McCormick and McNeil 1962). 

Psychostimulants (e.g., methylphenidate and dextroamphetamine with or without amphetamine) are the most effective agents in treating ADHD. Once the diagnosis of ADHD has been made, a stimulant medication should be used first line in treating ADHD (Fig. 39-1). Stimulants are safe and effective, with a response rate of 70% to 90% in patients with ADHD.3,13,14 Generally, a trial of at least 3 months on a stimulant is appropriate, and this includes dose titration to response... 

Initial response to short-acting stimulant formulations (e.g., methylphenidate and dextroamphetamine) is seen within 30 minutes and can last for 4 to 6 hours.13,14 This short duration of effect frequently requires that short-acting stimulant formulations be dosed at least twice daily, thus increasing the chance of missed doses and non-compliance. Further, patients using any stimulant formulation but especially shortacting formulations can experience a rebound effect of ADHD symptoms as the stimulant wears off.14... 

The (+)-enantiomer, DOV 21,947, is approximately twice as potent at NET and SERT as DOV 216,303. The minimum effective dose in both mouse tail suspension and rat FST models is 5mg/kg [87,88]. The (—)-enantiomer, DOV 102,677, is less potent than DOV 216,303 across all three transporters [89]. It is active in the FST in rats with a minimum effective dose of 20mg/kg. DOV 102,677 is as effective as methylphenidate in reducing the amplitude of the startle response in juvenile mice, without notably altering motor activity. It is reportedly under development for the treatment of alcohol abuse and alcoholism [68]. 

Garfinkel BD, Webster CD, Sloman L. (1981). Responses to methylphenidate and varied doses of caffeine in children with attention deficit disorder. Can J Psychiatry. 26(6) 395-401. 

Methylphenidate is typically initiated at a dose of 5 mg given twice a day. At each weekly visit, the dose can be increased by 2.5-5mg. Usually 20-30mg/day is sufficient, though as much as 60 mg per dose is occasionally needed. Many children with ADHD experience rebound hyperactivity at night when the daytime dose of medication has worn off. When this occurs, an after-school dose that is usually 25-50% of the earlier doses is helpful. The benefit of methylphenidate is often apparent within the first few days or so, and the dose can be increased weekly as needed. 

The prescribing physician should be notified immediately if tics or psychosis (usually paranoia) develop. The medication should always be stopped when psychosis occurs. We once said the same about tics, but recent research suggests that stimulants may not worsen tics. Methylphenidate is now available in a controlled-release preparation (Concerta), which can be prescribed once daily. One key advantage to once-daily dosing is not pharmacological, but rather that it avoids the stigma children may experience when they need to go to the school nurse s office to receive their afternoon dose. Focalin is the active isomer of methylphenidate. 

Dextroamphetamine (Dexedrine). Dextroamphetamine is the second most widely used stimulant and the most commonly used amphetamine in the United States. It is about twice as potent as methylphenidate and should be initiated in the treatment of ADHD at 2.5 mg taken twice daily with breakfast and lunch. Like other stimulants, the benefits of dextroamphetamine can be seen almost immediately. With weekly visits while starting treatment, the dose can be increased in 2.5-5 mg increments until the effective dose is found. Because dextroamphetamine is also slightly longer acting than methylphenidate, patients may be less likely to need an evening dose. If an after-school dose is used, then like methylphenidate it should be 25-50% of the daytime dose. 

First-line pharmacotherapy treatments include methylphenidate, dextroamphetamine, the mixed amphetamine salts (Adderall), and atomoxetine (see Table 8.3). When an early evening dose is indicated (e.g., completion of homework) it is typically at 25-50% of the doses prescribed earlier in the day. 

Methylphenidate (Ritalin, Concerta, Focalin). Methylphenidate was introduced in the late 1950s and is now the most widely used prescription stimulant. It was first used to treat ADHD in children but is also effective for narcolepsy. Like dextroamphetamine, methylphenidate should be started at 5 mg per dose given two to three times each day with meals. The average effective dose is 20-30 mg/day, but some patients require as much as 60 mg/day. The benefit of methylphenidate should also be apparent on the first day or so, and the dose can be increased every 5-7 days as needed. Focalin dosing is approximately half that of methylphenidate. 

Pemoline is a less potent stimulant than methylphenidate or dextroamphetamine. It should be initiated at 18.75 mg taken each morning with breakfast and can be increased in increments of 18.75mg every week or so. Typical dosing for pemoline ranges from 60 to 200mg/day in treating narcolepsy. Because pemoline is less potent than other stimulants, it is more likely to be ineffective, even at its higher doses. When pemoline does not relieve daytime sleepiness or sleep attacks, then the patient should be switched to a different stimulant. 

Methylphenidate is a CNS stimulant similar to amphetamine however, in usual doses it has a more expressed action on mental activity rather than physical or motor activity. In therapeutic doses it does not raise blood pressure, respiratory rate, or increase heart rate. All of these effects as well as a number of others are associated with general excitement of the CNS. Tremor, tachycardia, hyperpyrexia, and a state of confusion can result from using large doses. It is used in treating moderate depression and apathetic conditions, and also as an adjuvant drug for treating attention deficit disorder in children.Synonyms of this dmg are meridil, ritalin, and others. 

Patients new to methylphenidate The recommended starting dose of dexmethylphenidate for patients who are not currently taking racemic methylphenidate or for patients who are on stimulants other than methylphenidate is... 

Patients currently using methylphenidate For patients currently using methylphenidate, the recommended starting dose of dexmethylphenidate is half the dose of racemic methylphenidate. The maximum recommended dose is 20 mg/day (10 mg twice/day, immediate-release). 

Carcinogenesis In a lifetime carcinogenicity study carried out in B6C3F1 mice, racemic methylphenidate caused an increase in hepatocellular adenomas and, in males only, an increase in hepatoblastomas at a daily dose of approximately 60... 

Patients new to methylphenidate - The recommended starting dose for patients who are not currently taking methylphenidate or for patients who are on stimulants other than methylphenidate is 18 mg once/day. Dosage may be adjusted in 18 mg increments at weekly intervals to a maximum of 54 mg/day taken once/day in the morning for children 6 to 12 years of age, and a maximum of 72 mg/day (not to exceed 2 mg/kg/day) for adolescents 13 to 17 years of age. 

Recommended Dose Conversion from Methylphenidate Regimens to Concerta ... 

Previous methylphenidate daily dosage Recommended Concerta starting dose... 

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