Amphetamine salts

The proposed mechanism of ADHD pharmacotherapy is to modulate neurotransmitters in order to improve academic and social functioning. Pharmacologic therapy can be divided into two categories stimulants and non-stimulants. Stimulant medications include methylphenidate, dexmethylphenidate, amphetamine salts, and dextroamphetamine, whereas non-stimulant medications include atomoxetine, tricyclic antidepressants (e.g., imipramine), clonidine, guanfacine, and bupropion. 

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. 

Spencer TJ, Wilens TE, Biederman J, Weisler RH, Read SC, Pratt R. (2006) Efficacy and safety of mixed amphetamine salts extended release (AdderaU... 

Ambrosini PJ, Sallee FR, Lopez FA, Shi L, Michaels MA. (2006) LADD.CAT stndy gronp A community assessment, open-label stndy of the safety, tolerability, and effectiveness of mixed amphetamine salts extended release in school-age children with ADHD. Curr Med Res Opin 22 427-240. 

Kramer WQ Read SC, Tran BV, Zhang Y, Tnlloch SJ. (2005) Pharmacokinetics of mixed amphetamine salts extended release in adolescents with ADHD. CNS Spectrums 10 6-13. 

More research has been done on pharmacotherapy of ADHD in children and adolescents with MR than for other disorders. Reviews by Aman (1996), Arnold et al. (1998), and Handen (1993) summarize the psychostimulant research (methylphenidate, amphetamine, and magnesium pemoline). Of the 10 or more group studies of methylphenidate or dextroamphetamine in children, adolescents, and adults with ADHD and MR/ DD since 1980, all but one were positive and statistically significant. They showed substantial benefit for motor overflow, attention span, and impulsiveness. Improvements were also seen in cognitive performance, some measures of social behavior, and independent play. The sole negative study was of adolescents and adults without ADHD, most of them with profound MR (see Aman, 1996). No studies of mixed amphetamine salts (Adderall) or magnesium pemoline (Cylert) were found for this population (Arnold et al., 1998). 

McGough JJ, Biederman J, Wigal SB, et al Long-term tolerahility and effectiveness of once-daily mixed amphetamine salts (Adderall XR) in children with ADHD. J Am Acad Child Adolesc Psychiatry 44 530-538, 2005a... 

This group of medications has been studied for the treatment of hyperactivity or ADHD since 1936 and has consistentiy shown robust efficacy in more than 150 randomized ciinicai triais (RCTs) of schooi-aged chiidren. There are more than 3,000 citations and 250 reviews of stimulant treatment (63, 64 and 65). Robust short-term stimulant-related improvement in ADHD has been reported in 161 controlled RCTs, including five preschool, 140 school-age, seven adolescent, and nine adult studies (66). There were 133 trials with methylphenidate, 22 with dextroamphetamines, and six with pemoline. In addition, two studies found treatment with mixed amphetamine salts to be superior to placebo (67, 68). 

FIGURE 7-43. Adrenergic combo 4 NRI plus d,/-amphetamine. In this case, the NRI action at NE is double-boosted by a mixture of amphetamine salts containing the / as well as the d form of amphetamine. The /-amphetamine causes NE release. In addition, DA will be single-boosted by the (/-amphetamine, which causes DA release. 

The composition of amphetamine or dexamphetamine pills or capsules actually is a combination of the various types of amphetamine salts. For instance, the... 

Findling RL, Biederman J, Wilens TE, Spencer TJ, McGrough JJ, Lopez FA, Tulloch SJ, on behalf of the SL1381.301 and. 302 Study Groups. Short- and longterm cardiovascular effects of mixed amphetamine salts extended release in children. J Pediatr 2005 147 348-54. 

Adderall and Adderall XR are a mixture of d-amphetamine and l-amphetamine salts in the ratio of 3 1... 

Theoretically, this could lead to relatively more noradrenergic actions of the Adderall mixture of amphetamine salts than that of pure dextro-amphetamine sulfate, but this is unproven and of no clear clinical significance... 

Amphetamine Salt, Adderall, Adderall Extended Release (XR)... 

FIGURE 61-1. Algorithm for management of ADHD. Treat predominant disorder first, reassess, and consider alternative or adjunct medications for optimal symptom control. MPHD, methylphenidate DEX, dextroamphetamine MXA, mixed amphetamine salts TCA, tricyclic antidepressant AD, antidepressant. (Adapted from Pliszka et al, Pliszka et al, MTA Cooperative Group, Caballero, Daviss et al, State et al, Schur et al, Hughes et al, Muller-Vahl, and Jimenez-Jimenez. )... 

At this time, the preferred first-line drug therapy for ADHD is either methylphenidate, dexmethylphenidate, mixed amphetamine salts, or dextroamphetamine. Atomoxetine, bupropion, or TCAs are good options for those umesponsive to or unable to tolerate stimulants. Clonidine and guanfacine are third-line options or adjuncts that require careful cardiovascular monitoring. Mood stabilizers (e.g., lithium, divalproex, and carbamazepine) and atypical antipsychotics are adjuncts for control of aggression or comorbid bipolar disorder. Other agents require further investigation before their status in the treatment of ADHD can be fuUy determined. 

A critical part of the assessment must be to determine the patient s impairment at various times throughout the day to ensure that medication coverage overlaps with the time when the patient is most likely to benefit. As with all medication trials, it is important to start with a low dose of medication and keep increasing it slowly until the optimal risk-to-benefit ratio has been determined. Stimulant medication (methylphenidate, mixed amphetamine salts, and pemoline) and atomoxetine (a non-stimulant selective norepinephrine reuptake inhibitor, approved by the FDA for adult ADHD) are the first-line treatments of adult ADHD. Pemoline is not recommended as first-line treatment due to the risk of hepatoxicity. Stimulant drugs used to treat adults with ADHD are considered safe and effective, and have been well studied. There are several new long-acting formulations of... 

A hemorrhagic stroke has been attributed to the use of mixed amphetamine salts [9" ]. 

Kapetanovic S, Kim MA. Hemorrhagic stroke in a patient recently started on mixed amphetamine salts. Am J Psychiatry 2010 167(10) 1277-8. 

Winterstein AG, Gerhard T, Shuster J, Saidi A. Cardiac safety of methylphenidate versus amphetamine salts in the treatment of ADHD. Pediatrics 2009 124 e75-80. 

A review of 20 clinical trials published between 1979 and 2012 showed that subjects randomised to treatment with mixed amphetamine salts demonstrated a statistically significant increase in the resting heart rate [+5.7 bpm (3.6, 7.8), p < 0.0001] and systolic blood pressure [+2.0 mmHg (0.8, 3.2), p = 0.005] compared to subjects randomised to placebo [1 ]. A significant increased risk in resting heart rate >90 bpm [4.2% (n = 50) versus 1.7% (n = 8), odds ratio (OR) = 2.75 (1.3,6.7), p = 0.006] was found [l ]. A retrospective cohort study of new amphetamine users (n = 38,586) showed that the propensity score-adjusted hazard ratio for sudden death/ventricular arrhythmia was 1.18 (95% confidence interval [Cl] 0.55-2.54), for stroke 0.80 (95% Cl 0.44-1.47), for myocardial infarction 0.75 (95% Cl 0.42-1.35), and 0.78 for stroke/myocardial infarction (95% CEO.51-1.19) [2 ]. In a review of claims of privately insured young people, ages 6-21 years, without known cardiovascular risk factors (n = 171,126) that included all methylphenidate and... 

Product information AdderaU (R), mixed amphetamine salts. Saint-Laurent, Quebec Shire Canada, Inc. 

Martin PT, Corcoran M, Zhang P, Katie A. Randomized, double-blind, placebo-controlled, crossover study of the effects of lisdexamfetamine dimesylate and mixed amphetamine salts on cognition throughout the day in adults with attention-defidt/hyperactivity disorder. Clin Drug... 

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