Dextroamphetamine dosing

The relationship between dose and SLA was characterized by an inverted U-shaped curve for the phencyclinoids tested and dextroamphetamine. Geometric increases in cumulative IV doses produced nearly linear increases followed by decreases in SLA for each... 

FIGURE 5. Dose-response curves for the rate-increasing effects of phencyclinoids and dextroamphetamine on spontaneous locomotor activity. 

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... 

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. 

The side effects and potential for abuse with Adderall are essentially the same as for dextroamphetamine. We recommend starting Adderall at 2.5 mg twice a day or 5 mg each morning and then adding the second dose after a week or so. Using the extended-release formulation allows for the titration of the single dose with weekly adjustments as needed. 

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. 

Dextroamphetamine (Dexedrine) is commonly initiated at 5 mg taken two to three times daily before meals. Many patients will experience its benefits almost from the first day. The dose can be increased every 5-7 days until the effective dose is found. 

Dextroamphetamine does have several side effects that are characteristic of the stimulant class of medications. The most common side effects are insomnia, loss of appetite with associated weight loss, and occasional nausea and diarrhea. Taking the medication just before meals helps to minimize the nausea and diarrhea. To avoid insomnia, dextroamphetamine should rarely, if ever, be taken any later than 6 PM. Some patients will only be able to take the medication with breakfast or lunch, because a dinnertime dose will produce insomnia at bedtime. 

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. 

Dextroamphetamine is a powerful stimulant of the nervous system that manifests its effects by releasing dopamine and norepinephrine from presynaptic nerve endings, thus stimulating central dopaminergic and noradrenergic receptors. In certain doses it strengthens the excitatory process in the CNS, reduces fatigue, elevates mood and the capacity to work, reduces the need for sleep, and decreases appetite. 

The acute effects of psychomotor stimulant overdoses are related to their CNS stimulant properties and may include euphoria, dizziness, tremor, irritability, and insomnia. At higher doses, convulsions and coma may ensue. These drugs are cardiac stimulants and may cause headache, palpitation, cardiac arrhythmias, anginal pain, and either hypotension or hypertension. Dextroamphetamine produces somewhat less cardiac stimulation. Chronic intoxication, in addition to these symptoms, commonly results in weight loss and a psychotic reaction that is often diagnosed as schizophrenia. 

Methylphenidate and D-amphetamine are both short-acting compounds, with an onset of action within 30 to 60 minutes and a peak clinical effect seen usually between 1 and 2 hours after administration, lasting 2 to 5 hours. Therefore, multiple daily administrations are required for a consistent daytime response. The amphetamine compound Adderall, the sustained-release preparations of methylphenidate and dextroamphetamine, and pemoline are all intermediate-acting compounds with an onset of action within 60 minutes and a peak clinical effect seen usually between 1 and 3 hours after administration and maintained for up to 8 hours (8 hours with metadate C.D. and Ritalin LA 12 hours with Concerta), allowing for a single dose for the entire school day. Adderall XR is a 12 hour preparation. 

Psychostimulant medication can be useful in the treatment of severe, acute pain, such as that seen during a sickle cell crisis (Yaster et al., 2000). Dextroamphetamine and methylphenidate are also effective as adjuvants, as they have independent analgesic effects, and potentiate the effects of opioid analgesics. The increase in alertness afforded by the use of psychostimulants can also allow the use of larger doses of opioids (Yaster et al., 2000). Methylphenidate and dextroamphetamine have been used to diminish the sedative effects of opioid analgesic medication (Yee and Berde, 1991) in adolescent patients with malignancies or sickle crisis, and may also potentiate the effects of analgesics. Doses used by Yee and Berde (1991) were 2.5 to 10 mg bid of methylphenidate, or 2.5 to 5 mg bid of dextroamphetamine. 

There is a clinical impression that psychostimulants may be helpful in HIV- or AIDS-related affective syndromes (487, 488). Thus, methylphenidate 10 to 20 mg per day (up to 40 mg per day) or dextroamphetamine 5 to 15 mg per day (up to 60 mg per day) has been helpful in patients with mild depression who also show symptoms of social withdrawal, fatigue, and apathy, as well as mild cognitive impairment. At times, the combination of low-dose antidepressant and psychostimulant may be more effective and less likely to induce adverse CNS effects. 

The usual chronic oral dose of dextroamphetamine is 5 mg, 2-3 times daily however, studies employing the drug to prolong wakefulness and performance typically employ larger doses in the range of 10-20 mg (100). Prior to administering normal therapeutic doses to humans, a test dose of 2.5 mg is recommended since toxic manifestations have been seen (as an idiosyncrasy) after even a 2-mg dose, although reactions are rare with doses under 15 mg. 

---