DEXTROAMPHETAMINE AMPHETAMINE TRIAL

Additional information regarding dosing and medication pharmacokinetics are available in Table 1. While there is long-standing clinical experience of treatment benefit, this needs to be weighed against potential risks.

Again, lack of rigorous testing makes evaluation of the amphetamines for EDS in narcolepsy challenging. Similar to methylphenidate, initial studies of these medications were small, but did show benefit for reducing sleepiness and enhancing performance in a dose-dependent manner ( Mitler et al., 1986, 1990, 1993 Mitler and Hayduk, 2002). They are also a US DEA Schedule IIN controlled substance. Additionally, these medications carry an FDA Boxed warning for high potential of abuse and sudden death with misuse.

Serious cardiovascular adverse effects in healthy adults are unlikely to occur. Adverse events include misuse/abuse, serious CV complications including MI, peripheral vascular disease, cerebrovascular accident, lowered seizure threshold, and psychiatric disorders.

Significant medication interactions exist with MAOIs, sibutramine, serotonergic agents, and CYP2D6 inhibitors. Contraindications are similar to methylphenidate and include advanced or symptomatic CV disease, hyperthyroidism, and history of addiction. These medications are also not dialyzable therefore, they should not be used in end-stage renal disease and dose adjustments are needed with severe renal impairment. While there are no recommended dose adjustments with liver impairment, caution with dosing should be used in this setting. These medications are hepatically metabolized via CYP P450s and renally eliminated. For the IR mixed amphetamine salts, peak concentration is reached at 3 h whereas peak concentration for the ER formulation is 7 h. Half-life elimination varies by enantiomer, with d-amphetamine taking 11 h, and l-amphetamine lasting 13–14 h. Transition to ER formulations can decrease frequency of dosing however, some patients still require a second dose later in the day. Usual dosing for dextroamphetamine and mixed amphetamine salts starts at 10 mg and can be titrated up to a maximum of 60 mg/day in divided doses. Extracellular levels of norepinephrine rise in a dose-dependent manner in the prefrontal cortex with administration of amphetamines additionally dopamine levels rise in the striatum ( Heal et al., 2013). These medications increase dopamine, norepinephrine, and to a lesser extent serotonin levels via increased release at the synaptic terminals in addition to also blocking reuptake of monoamines and likely inhibiting monoamine oxidase ( Heal et al., 2013). d-Amphetamines are the dextro-enantiomer, which is more potent than the levo-enantiomer ( Heal et al., 2013). Bhanu Prakash Kolla, in Reference Module in Biomedical Sciences, 2021 2.3.2.2 AmphetaminesĪmphetamines including dextroamphetamine ( d-amphetamine) and mixed amphetamine salts (Adderall™) have been used for narcolepsy even prior to methylphenidate (since 1930s) ( Szabo et al., 2019). It is notable that summer and other briefer drug holidays produced consistent improvements in tic severity even in subjects whose tics were mild while on stimulants. Long-term, open follow-up of this study supported an advantage for MPH compared to dextroamphetamine. Dextroamphetamine showed significantly greater effects upon tic severity compared to placebo, while the effects of MPH upon tic severity were indistinguishable from placebo. A significant decrease of hyperactivity was seen on ADHD measures. Weekly dextroamphetamine doses were 7.5, 15, and 22.5 mg/dose twice daily.

DEXTROAMPHETAMINE AMPHETAMINE TRIAL

(1997) conducted a crossover trial of 3 weeks to compare MPH and dextroamphetamine to placebo on tic severity in boys with ADHD and TS or chronic tic disorder. The pharmacodynamics effects of dextroamphetamine include reuptake inhibition of monoamines and direct stimulation of release of dopamine and noradrenaline. Renata Rizzo, Mariangela Gulisano, in International Review of Neurobiology, 2013 4.2.2 Dextroamphetamine

Dextroamphetamine amphetamine