Vyvanse: The Next Generation of ADHD Medication
James G. Brown
South University
December 6, 2012

Historical Background
“Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric disorder associated with significant impairments in occupational, academic, neuropsychological, and social functioning” (Mattingly, 2010, p. 316). ADHD is typically considered as a childhood disorder, however, “symptoms persist into adulthood in up to 65% of children with ADHD” (Mattingly, 2010, p. 316). Although it is still a relatively rare condition, in the United States, it affects “4.4% [of the population], or 9 million adults” (Mattingly, 2010, p. 316). There appears to be some evidence that the condition is sex linked, as “boys are diagnosed with ADHD 2 – 4 times as frequently as girls” (Berman, Kuczenski, McCracken and London, 2009, p. 4).

Adults affected by ADHD are often misdiagnosed and of those who are correctly diagnosed, approximately only 10% receive any treatment (Mattingly, 2010, p. 316). Depending on the severity “untreated ADHD…[can help create] a pervasive pattern of repeated difficulties or impairment. Continuing impairment from ADHD may cause individuals to struggle with academic, career, and personal goals, or may cause significant difficulty within interpersonal relationships” (Mattingly, 2010, p. 316.) In addition, ADHD has a high level of comorbidity with depression, various anxiety disorders, as well as a greater likelihood of engagement in criminality, substance abuse or other risk taking behavior. (Mattingly, 2010).

“Pharmacotherapy continues to be the mainstay of treatment for ADHD” (Mattingly, 2010, p. 316). Although the diagnosis of ADHD “is not [clearly] defined by a biological marker”(Duncan, Miller, & Sparks, 2004, p. 156) there is preliminary evidence that the condition of ADHD has significant biological components regarding brain mass, and therefore a better fit into the medical model of treatment (Ingersoll & Rak, 2008).

There are many psychopharmacological options for the maintenance treatment of ADHD. The medications break down into two classes: stimulants and non-stimulants. Stimulant medication tends to be the preferred choice of treatment of the medical community (Mattingly, 2010) and “have unequivocally established their efficacy over placebo” (Duncan, et al, 2004, p. 156). The newest and faster growing ADHD medication on the market today is Vyvanse. Vyvanse is the brand name of lisdexamfetamine dimesylate. It was developed by Shire Pharmaceuticals and was approved for the treatment of adults with ADHD by the Food and Drug Administration (FDA) (Laughren, 2008). It is being promoted by Shire Pharmaceuticals as a replacement for Adderall-XR, which lost its patent in 2007 (Shire Pharmaceuticals, 2010).

Vyvanse “was developed with the goal of providing long duration of effect that is consistent throughout the day with reduced potential for abuse” (Kaminski & Krishnan, 2009, p. 420). The reason why there is less potential for abuse with Vyvanse than with other ADHD stimulant-based medication is that the psychotropic ingredient, dextroamphetamine (d-amphetamine) “does not become available through mechanical manipulation, such as crushing or simple extraction” (Kaminski & Krishnan, 2009, p. 420) and only becomes activated after being ingested in the body.

Mechanism of Action

What makes Vyvanse different than Adderall or other earlier forms of medication for ADHD is its “novel mechanism of delivery” (Lyseng-Williamson, 2010, p. 1.) Unlike other ADHD medications, Vyvanse is a prodrug. A prodrug means that the psychoactive agent is inactive and subsequently converted into its active form by the body’s own natural metabolic processes. In the case of Vyvanse, after ingestion it “is rapidly absorbed from the gastrointestinal track and converted primarily in blood due to the hydrolytic activity of dextroamphetamine, which is responsible for the drug’s activity” (Shire Pharmaceuticals, 2012, p. 5) and therapeutic effect. This metabolic conversion process causes a delayed reaction and a lower plasma concentration which allows Vyvanse to have a longer half-life and less abuse potential than an immediate-release amphetamine (Jasinski & Krishnan, 2009). In addition, due to the fact that the therapeutic effect of this medication only takes place in the intestinal tract, injecting it intravenously or ingesting the drug through insufflation (snorting) should not produce a euphoric effect as is possible in the case of other amphetamines.
Like all amphetamines, “the mode of therapeutic action in…(ADHD) is not known” (Shire Pharmaceuticals, 2012, p. 5). “Amphetamines readily pass the blood-brain barrier to reach their primary sites of action in the brain” (Berman, et al., 2009, p. 3) and it is theorized that “amphetamines block the reuptake of [the neurotransmitters] norepinephrine and dopamine into the presynaptic neuron and increase…[their availability] in the extraneuronal space” (Shire Pharmaceuticals, 2012, p. 5). Essentially amphetamines balance the dopamine and norepinephrine neurotransmitters in the brain, which help increase alertness, attentiveness, and concentration. This can result in improving cognitive performance while decreasing lethargy.

Pharmacokinetics

Vyvanse “has predictable pharmacokinetic characteristics” (Mattingly, 2010, p. 318). Vyvanse “is the first long-acting prodrug stimulant…for the treatment of ADHD” (Mattingly, 2010, p. 317). Vyvanse is manufactured in single doses of 30, 50, and 70 mg. capsules. However, whatever dose is administered, it typically reaches peak blood levels within 3 1/2 hours (Shire Pharmaceuticals, 2012). In addition, the psychoactive component, d-amphetamine, has a half-life of approximately 12 hours, (Shire Pharmaceuticals, 2012) which indicates that, for example, once a patient takes 50 mg. of Vyvanse, he or she will still have 25 mg. in his or her body 12 hours after taking his or her initial dose.

“Vyvanse has a lower pharmacokinetic variability and has a slightly longer duration than other delayed-release amphetamine medications, but requires higher doses” (Berman, et al, 2009, p. 3). In comparison with Adderall-XR, the FDA approve[s] doses up to 20 mg. a day due to the lack of evidence for clearly superior benefits from higher doses” (Berman, et al, 2009, p. 3). However, in the case of Vyvanse, “once-daily doses of 30, 50, 70 mg….has been shown to be effective in improving symptoms of ADHD” (Janinski, D., & Krishnan, S. 2009, p. 420) and “is approved for up to 70 mg [per] day for school-aged children” (Berman, et al, 2009, p. 125).
Pharmacotherapy

Vyvanse is primarily indicated for the treatment of ADHD in children, adolescents and adults (Shire Pharmaceuticals, 2012). It is also used for the treatment of narcolepsy and other sleep disorders (Berman et al, 2009.) Vyvanse may not be appropriate for persons with “known hypersensitivity to amphetamine products… [or known to have] anaphylactic reactions, Stevens-Johnson Syndrome, angioedema, and urticarial” (Shire Pharmaceuticals, 2012, p. 2). In addition, special caution should be used with individuals currently taking monoamine oxidase (MAO) inhibitors with Vyvanse as mixing the two substance could “result in hypertensive crisis,” (Shire Pharmaceuticals, 2012, p. 2). This occurs when blood pressure suddenly spikes so high that organ damage can occur. If this crisis occurs, emergency medical attention may be needed in order to prevent organ damage. As a safety precaution, “Vyvanse should not be given for at least 14 days after discontinuation of an MAO inhibitor” (Shire Pharmaceuticals, 2012, p. 2).

In addition, Vyvanse should not be given to individuals with known “cardiac abnormalities or other serious heart problems” (Shire Pharmaceuticals, 2012, p. 2). Vyvanse has been known to increase blood pressure and therefore caution should be taken by individuals with pre-existing hypertension. Individuals with co-morbid conditions such as Bipolar Disorder, and a history of psychosis should not take Vyvanse as it may exacerbate symptoms of those disorders. If after taking Vyvanse, there is an emergency of new psychotic or manic symptoms, Vyvanse should be discontinued and the individual should immediately consult a medical professional (Shire Pharmaceuticals, 2012).

Effectiveness

Participants
In 2010, a study on the effectiveness of Vyvanse was conducted. In this study, adults participants, who were previously diagnosed with ADHD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) and “further validated by a comprehensive psychiatric evaluation that included a semi-structured interview based on the Adult ADHD Clinical Diagnostic Scale, version 1.2 (ACDS v. 1.2)” (Wigal, Brams, Gasior, Gao, Squires, & Giblin, 2010, p. 2) participated in a 4-week, double-blind, placebo controlled, clinical trial. “It was designed to assess duration of efficacy, tolerability, and safety of…Vyvanse…in adults with ADHD” (Wigal et al, 2010, p. 3).

“The study comprised of four phases: screening and washout (6 weeks); open-label dose optimization (4 weeks); double-blind crossover (2 weeks) which included 2 full-day evaluations” (Wigal et al, 2010, p. 3). The study began with 142 subjects; however, only 103 completed the study. Of the original cohort, 39 discontinued prematurely due to a natural disaster (i.e. hurricane) or due to various health concerns or personal reasons.
Drugs

According to Wigal et al, the study’s primary objective was to assess and evaluate Vyvanse’s efficacy versus placebo (2010). No other psychotropic substance was used to evaluate the effectiveness of Vyvanse. In the open-label dose optimization phase, all adult participants were given Vyvanse was administered in doses of 30, 50, and 70 mg. until optimization was achieved. Upon receiving Vyvanse, the subjects who received an intolerable response, they were permitted to reduce their dose by 20 mg. until the dose was acceptable to them. Those who received a favorable response were permitted to increase their dose to the maximum dose of 70 mg. (Wigal et al, 2010, p. 6).

In the second phase, “subjects…entered a 2 week double-blind crossover phase” (Wigal et al, 2010, p. 6) where all participants were given Vyvanse “for 7 days followed by placebo for 7 days or placebo for 7 days followed by their optimized dose of [Vyvanse]” (Wagal et al, p. 6).

Outcomes

The results were that the participants receiving Vyvanse reported and were determined to have greater improvement in reducing signs and symptoms of ADHD that those who received the placebo. The only negative effect was that “during dose optimization [participants receiving treatment with Vyvanse experienced]…decreased appetite, dry month, headache and insomnia” (Wigal et al., 2010, p. 1). Reference:

Berman, S.M., Kuczenski, R., McCracken, J.T. &; London, E.D. (2009). Potential adverse effects of amphetamine treatment on brain and behavior: A review. Molecular Psychiatry, 14, 123-142.

Duncan, B.L., Miller, S.D., & Sparks, J.A. (2004). The heroic client. San Francisco, CA: Jossey-Bass.

Howland, R.H. (2008). Lisdexamfetamine: A prodrug stimulant for adhd. Journal of Psychosocial Nursing, 46(8), 19-23.

Ingersoll, R.E., & Rak, C.F. (2006). Psychopharmacology for the helping professions: An integral exploration. Belmont, CA: Brooks/Cole.

Janinski, D.R., & Krishnan, S. (2009). Abuse liability and safety of oral lisdexamfetamine dimesylate in individuals with a history of stimulate abuse. Journal of Psychopharmacology, 23(4), 419-427. doi:10.1177/0269881109103113

Laughren, T. (2008). Approval of vyvanse. Department of Health and Human Services: Food and Drug Administration.

Mattingly, G. (2010). Review article: Lisdexamfetamine dimesylate: A prodrug stimulant for the treatment of adhd in children and adults.
MBL Communications Inc., 315-318.

Lyseng-Williamson. K.A. (2010). Lisdexamfetamine dimesylate: A guide to its use in attention-deficit hyperactivity disorder. Drugs & Therapy Perspectives, 26(10), 1-5

Wigal, T., Brams, M., Gasior, M., Gasior, M., Gao, J., Squires, L., & Giblin, J. (2010). Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: Novel findings using a simulated adult workplace environment design. Behavioral and Brain Functions, 6(34), 1 -14.

Vyvanse® (lisdemamfetamine dimesylate) capsules. (2012). Highlights of prescribing information: A Medication Guide. Wayne (PA): Shire Pharmaceutical Inc., U.S.