Vyvanse (Lisdexamfetamine Dimesylate) – Dale Mortimer, M.D.

Introduction

Vyvanse (lisdexamfetamine dimesylate) is the first long–acting, water–soluble, schedule II, pro–drug medication which is now FDA–approved for the treatment of attention deficit/ hyperactivity disorders (“ADHD”) in children, adolescents and adults.

Once Vyvanse is swallowed and then absorbed into the portal circulation, Vyvanse is converted over the course of the day to the active ingredient, i.e., dextroamphetamine. Unlike other longer–acting stimulant options available for the treatment of ADHD, the “time–release” properties of Vyvanse are “built into the molecule.” And, because of the particular design of the Vyvanse molecule, Vyvanse is highly unlikely to cause euphoria, substance abuse, or chemical dependency.

Vyvanse is manufactured by Shire Pharmaceuticals. In 2007, Vyvanse was FDA–approved for marketing as safe and effective for treatment of children with the diagnosis of ADHD. In 2008, Vyvanse was FDA–approved for the treatment of adults with childhood–onset ADHD. And in 2011, Vyvanse was then FDA–approved for the treatment of adolescents with ADHD. Vyvanse patent expires in 2023.

Since 2007, I have prescribed Vyvanse to over 686 patients, with patient ages ranging from 9 to 68 years of age. When I last “ran the numbers” on my patient database, 66% of my patients who have tried Vyvanse have had a robust response [e.g., much improved: attention, concentration, motivation, time management, academic performance, and impulse control – as supported by patient/ teacher/parent/boss/spouse report, clinical assessment, and 4–minute duration, computerized continuous performance task. About 4% of my patient population have reported lack of perceived benefit from Vyvanse at any dose tried; and about 30% of those prescribed Vyvanse did not continue with the medication for various reasons – as discussed below.

What is most notable to me is that 47% of my ADHD patients have reported better results with Vyvanse than with any other stimulant or non–stimulant tried for management of their ADHD symptoms. Many of these ADHD patients have reported to me that they prefer the “more even” benefit of Vyvanse throughout the day; other patients have reported that they can tolerate Vyvanse better than other stimulants tried (i.e., typically Vyvanse has less severe adverse effects on sleep and appetite than does, say, Adderall). I have been able to confirm my patients’ reports of Vyvanse efficacy with my computerized continuous performance task test – which objectively measures attention, impulsivity, and reaction time (i.e., the 4–minute continuous performance task).

Since Vyvanse is relatively new, Vyvanse may not be as familiar to primary care physicians, pharmacists, and pharmacy benefits managers at for–profit companies as are the other, older ADHD treatment options (e.g., Dextrostat, Dexedrine Spansules, Adderall, Desoxyn, methylphenidate, Metadate CD, Ritalin LA, Concerta, and Daytrana). This essay is an abridged version of my current reading of published clinical studies on Vyvanse – plus my current clinical experience with Vyvanse since 2007.‍

Pharmacoeconomics:

Manufacturer: Shire Pharmaceuticals; Shire Development, Inc. and Shire US, Inc. Packagers: New River Pharmaceuticals, Inc.; Pantheon, Inc.; Physicians total Care Inc. Quality Care; Shire, Inc.

Shire’s patent on Vyvanse is scheduled to expire in 2023.‍

Molecular Structure

IUPAC Name: (2S)-2,6-diamino-N-[(2S)-1-phenylpropan-2-yl]hexanamide

<pastedGraphic.png>

Brief History of the Amphetamines

Prescribing amphetamines (i.e., dextroamphetamine, levoamphetamine, and methamphetamine) for legitimate medical conditions is not new. Amphetamine (which is a racemic mixture of dextro– and levo–amphetamine) was first synthesized in 1887. In 1932, amphetamine was first used and marketed as an over–the–counter bronchodilator medication for asthma. In 1937, amphetamine (as Benzedrine – which is a racemic mixture of the dextro– and levo–amphetamine isomers) was introduced in tablet form to treat narcolepsy and post–encephalitic parkinsonism.

A methylated version of amphetamine is methamphetamine, which was first synthesized in 1919, and was initially available as an over–the–counter decongestant. Methamphetamine (its current brand name is “Desoxyn”) has been a prescription medication available for over sixty years. As far as I can determine, methamphetamine was first reported effective as an antidepressant in 1948. Since 1970 (or earlier), methamphetamine (Desoxyn) has been FDA–approved for the treatment of endogenous obesity and what is now called ADHD. Methamphetamine (Desoxyn) is also frequently prescribed off–label for the treatment of narcolepsy, chronic pain, and depressed mood.

Benzedrine is a racemic mixture of dextroamphetamine and its enantiomer levoamphetamine. In the 1930s, Benzedrine was found effective in the treatment of hyperactive children. Its efficacy in the management of hyperactive boys was published by Bradley in 1937. Benzedrine was not available for many decades, having been replaced by Dextroamphetamine (e.g., Dextrostat and Dexedrine Spansules) and mixed amphetamine sales (Adderall IR and XR). However, in 2015, Benzedrine was resurrected, marketed under its newly minted name: Evekeo.

In the 1960s, Obetrol (a combination of amphetamine salts and methamphetamine) was FDA approved for the treatment of obesity. As a consequence of the Controlled Substances Act of 1970, Obetrol was reformulated, and methamphetamine was eliminated from the compound. After 1970, Obetrol continued to be FDA–approved for the treatment of obesity as mixed amphetamine salts in a 3:1 ratio of dextroamphetamine and levoamphetamine. In 1994, Shire bought the manufacturing rights to Obetrol,; Shire then renamed Obetrol to the much more catchy name, Adderall (presumably for treating “all” cases of “ADD”). The Adderall tablet (“IR” for immediate release) was then aggressively marketed by Shire for the treatment of ADHD. Then, in 2001, along came the Adderall time–released capsule (Adderall XR).

In 1958, dextroamphetamine was FDA approved for the treatment of both narcolepsy and ADHD. For many decades, dextroamphetamine has been available for prescription as either Dexedrine (brand) or Dextrostat (generic) There is also an very old “time release” form of dextroamphetamine available now as Dexedrine Spansules. The Spansules’ usual duration of action is about 5 hours per dose. Then in 2015, dextroamphetamine options increased with the introduction of immediate–release Zenzedi tablets, ranging from 2.5 mg to 30 mg tablets.‍

Pharmacokinetics of Vyvanse (i.e., what the body does to the medication)

Vyvanse is a pro–drug. Once ingested, the Vyvanse is rapidly absorbed in the GI tract where it is converted via hydrolysis in the portal circulation by red blood cell enzymes to dextroamphetamine and lysine. Dextroamphetamine is the active ingredient. Lysine is an essential amino acid found in relatively high concentrations in such foods sources as soybeans, peas, lentils, and sardines.

A clinically significant response to Vyvanse dose is usually seen within 2 hours of ingestion of Vyvanse. Clinical trials have found Vyvanse effective for managing ADHD symptoms for up to 13 hours after ingestion in children, and up to 14 hours in adults. In my patient population, the majority of those who find a benefit with Vyvanse report that it lasts from morning to bedtime. A minority (about 5%) of my clinical population report that the benefit starts to wane at about 8 hours after ingestion.

Vyvanse is unlikely to be affected by gastric contents, gastric pH, or GI transit time.

The majority of dextroamphetamine is excreted unchanged in the urine, without significant levels of active metabolites. It will show up as dextroamphetamine in urine drug tests.

Volume of distribution: unknown

Protein binding: unknown

Route of elimination: renal excretion

Half–life: the plasma elimination half–life of Vyvanse typically averages less than one hour.

Clearance: unknown‍

Pharmacodynamics of Vyvanse (i.e., what the medication does to the body)

As stated at www.drugbank.ca:

“Lisdexamfetamine is a pro-drug of dextroamphetamine. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. Norepinephrine and dopamine contribute to maintaining alertness, increasing focus, and sustaining thought, effort, and motivation. However, the exact therapeutic action in ADHD is not known.”‍

Formulations of Vyvanse

Vyvanse is a powder, and is currently available in capsules of 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. In addition to swallowing the capsules, Vyvanse is also FDA–approved for dissolving the Vyvanse powder in water. The Vyvanse powder is readily dissolved in water (or in juice), and has a mildly sour taste (described by my patients as tasting like weak lemonade). The flecks that float in the water won’t dissolve – these flecks are either some filler or some binder which has been added to the Vyvanse; the flecks are inert ingredients. There is no need to attempt to swallow these flecks (which quickly settle to the bottom of the water container, anyway). The solution of Vyvanse in water or juice is stable and as far as anyone knows, the solution does not need to be refrigerated. There is nothing special about the capsule shell – the shell just envelops the active ingredient.‍

Dosing range for Vyvanse

I have been able to use a very accurate, short and convenient computerized continuous performance task test to help identify or confirm optimal Vyvanse doses. Based on my “number crunching” of 60 of my ADHD patients who have had good results with Vyvanse, the dose of Vyvanse producing optimal results has been 70 mg daily (with one standard deviation of plus/minus 60 mg). Thus, the majority – but certainly not all – of my patients have been able to find their optimal Vyvanse dose using either one or two capsules daily.

My current often–prescribed “recipe” for ADHD patients who are initiating a Vyvanse trial is as follows:

Cost of Vyvanse

Without medical insurance pharmacy benefits coverage, Vyvanse costs close to $10 per capsule (for any size Vyvanse capsule).

Since the “launching” of Vyvanse in 2007, the manufacturers of Vyvanse (originally, Shire Pharmaceuticals), have offered various voucher programs to help patients with the costs of Vyvanse. These various voucher programs to help patients with the costs of Vyvanse may change every year.‍

Therapeutic blood levels of Vyvanse

Not clinically useful.‍

Adverse effects of Vyvanse

Reported – or anticipated – adverse effects are those which are typically found with the other ADHD stimulant medications: less appetite – especially for lunch – is probably the most common side effect. Insomnia is also sometimes reported with Vyvanse (especially if Vyvanse is taken later in the day – i.e, after high noon).

Adverse effects reported in published clinical studies which were found more frequently with Vyvanse than with placebo include: irritability, upper abdominal pain, vomiting, dry mouth, and weight loss. In published clinical trials, the majority of these side effects were mild, tolerable, and resolved within a week of continued Vyvanse use. Headaches have not been found to be more frequent with Vyvanse than with placebo.

Consistent with the literature from the clinical trials, the most common clinical reasons given for stopping Vyvanse in my clinical population have been: difficulty falling asleep and decreased appetite. About 30% of my patients discontinued Vyvanse. Some discontinued Vyvanse because of the cost of the medication. (As a result of our most recent national recession, many patients lost their jobs, and subsequently lost their medical insurance coverage for medications.) Others discontinued Vyvanse because another less expensive stimulant worked as well or better than Vyvanse. And some discontinued Vyvanse because of adverse side effects (i.e., from decreased appetite, difficulty falling asleep, worsening tics, or “I just didn’t care for it”).

In my patient population, it has been the cost of the medication which has probably been the most frequently verbalized reason for patients discontinuing Vyvanse.

Among my patients who have tried doses of Vyvanse which, in retrospect, were higher than optimal for that particular patient, the patients simply did not care for the results. In those patients who have tried a supra–optimal Vyvanse dose, they consistently describe the experience of higher Vyvanse doses in almost exactly these words: “I just didn’t like the higher dose.” Patients who tried higher doses and “didn’t like it” did not complain of significant headaches, palpitations, jitteriness, stomach–aches, or light–headedness – they just didn’t care for the Vyvanse doses greater than that which was, in retrospect, the optimal for them.

Besides decreased appetite, and insomnia, a minority of patients (or their parents) report the following adverse effects associated with Vyvanse (which can also be seen with the other stimulants used for ADHD treatment): With Vyvanse, a minority of patients reported that the patient was: too calm; too talkative; sad/ tearful; irritable; had dry mouth; experienced cold hands/ feet; and demonstrated worsening tic–like behaviors (e.g., eye blinking; fingernail ripping; lip and cheek chewing; and teeth clenching).‍

Potential for Vyvanse abuse

While the FDA has classified Vyvanse as a Schedule II medication, this decision appears to be more politically motivated than based on clinical evidence of documented abuse potential.

Vyvanse is a prodrug and a relatively long molecule. Because Vyvanse is both a very long molecule, and because Vyvanse is water soluble (i.e., Vyvanse is not lipid soluble), Vyvanse does not pass through an intact blood–brain barrier into the human brain. To become pharmacologically active, Vyvanse must to be swallowed, and then be converted from pro–drug to dextroamphetamine via enzymatic cleavage found on red blood cells (and maybe peptidases in the gut). Thus, if Vyvanse is smoked, snorted, or injected, it cannot pass through an intact blood–brain barrier into the brain. Thus, I must conclude that caffeine is more likely to cause euphoria than would Vyvanse. (And, of course, daily caffeine use is more likely to cause chemical dependence than is daily Vyvanse use.)

Curiously enough, those with a valid diagnosis of ADHD (or narcolepsy, chronic pain or depression) seldom – if ever – report euphoria from any of the methylphenidate or amphetamine preparations currently available by prescription. Euphoria from the methylphenidate or amphetamine preparations currently used for the treatment of ADHD is so rare in those with a valid diagnosis of ADHD that if a patient did report euphoria, a physician could probably see his or her case report published in a medical journal.‍

Safety of Vyvanse

As I noted in the introduction, stimulants (including Vyvanse) used in the treatment of ADHD are considered by child & adolescent psychiatrists to be some of the safest medications used in all of medicine. Looking at the Vyvanse literature, I note that in their 2011 published study of the safety and efficacy of Vyvanse in ADHD adolescents (with Vyvanse doses up to 70 mg daily), Findling and colleagues found a slight increase from baseline to endpoint in mean electrocardiogram–measured heart rate (2-3 beats/ minute). No participant had a QTcF (QT interval corrected using the Fridericia method – which is less likely to be influenced by extremes of heart rate) of > 480 milliseconds. Overall, Findling and colleagues reported no clinically meaningful trends observed in EKG interval data in those patients prescribed Vyvanse (no surprise there).

Published clinical trials addressing the cardiovascular effects of stimulants such as Vyvanse have repeatedly found that stimulants cause statistically significant but clinically insignificant effects on blood pressure (i.e., 1–3 mm change systolic and diastolic pressures with Vyvanse compared to placebo) and clinically insignificant effects on pulse (i.e., average pulse change of 3 beats per minute with Vyvanse compared to placebo). To put this in perspective: a can of Pepsi, a cup of coffee, or a night of partial sleep deprivation (i.e., only 4 hours of sleep) predictably increases pulse and blood pressure to a greater extent than does a prescribed ADHD medication such as Vyvanse at doses commonly used to optimally manage ADHD.

To date (i.e., as of November 2017), published studies and reviews have convincingly shown that neither Vyvanse nor or any other stimulant used to treat ADHD in children, adolescents or adults causes seizures, tics, or lethal cardiovascular events in any age group. Stimulants’ effects on blood pressure, pulse, height and weight might be statistically significant but they are clinically insignificant. Those who claim otherwise are not familiar with the current published literature on this topic, and these individuals who maintain this dangerous and uninformed position should in my opinion be both geeked and fleered.‍

Contraindications

Those with previously identified, pre–existing structural heart pathology who are prescribed stimulants may be at increased risk for sudden death. However, this is a political opinion lacking any convincing clinical data. And since I believe that this position is a political one, then there will never be sufficient numbers of clinical studies which will convince the uninformed otherwise. Furthermore, do be aware that I doubt than any ethics committee will ever approve a proposed clinical study seeking to assess the cardiovascular effects of stimulants in ADHD patients with a history of congenital heart disease, ischemic heart disease, angina, cardiomyopathy, ventricular arrhythmias, heart failure, stroke, and/or myocardial infarction.‍

Potential risk in suicide or overdose

Despite what the mass media might insinuate to the contrary, the reality is that – as is the case with the other stimulants used in the treatment of ADHD and narcolepsy – there is not any dose of Vyvanse which has been identified as being a lethal dose for humans. Rats have been given oral Vyvanse doses up to 1,000 mg/ kg without lethality (– the equivalent dose for humans is about 80,000 mg Vyvanse given to an average sized – that is, obese – adult).‍

Drug interactions

Vyvanse mixes without any serious problems with other amphetamines such as dextroamphetamine (Dextrostat, Dexedrine Spansules, and Zenzedi), mixed amphetamine salts (Adderall) and methamphetamine (Desoxyn). As far as I am aware, there are no published studies looking at the safety of combining Vyvanse with methylphenidate (e.g., Ritalin) products. However, many clinicians have prescribed combinations of amphetamines and methylphenidate products to their patients for decades without serious adverse events.

Vyvanse may be safely prescribed with monoamine oxidase inhibitors if prescribed cautiously and carefully by a smart, seasoned clinician.‍

Withdrawal effects

As is the case with any of the other stimulants used in the treatment of ADHD, end of the dose “rebound” can occur with Vyvanse. But end–of–the dose rebound with Vyvanse appears to be rare. (But then again, end–of–the–dose rebound irritability is not really withdrawal.)

Every night as a patient taking a stimulant sleeps, he or she metabolizes and/or excretes just about all of the day’s stimulant dose. And every morning upon awakening and before taking his/ her morning dose, the patient has effectively zero benefit from the stimulant ingested during the previous day. [Compare this to waking up in the morning without first putting on your eyeglasses. No medications (or no eyeglasses) – means no focus for that day. Take the stimulant (or put on the eyeglasses) – and the previous benefit returns for no more than the duration of that day.]‍

Diagnostic lab tests altered by Vyvanse.

In those taking Vyvanse, one should expect urine and blood drug tests to be positive for dextroamphetamine.‍

Case reports of safety and efficacy of Vyvanse in doses exceeding FDA–advertising limits

In reviewing at a sample of 225 of my patients who have reported on their experience with Vyvanse, about 70% report that they have found Vyvanse more effective or better tolerated than other stimulants tried (e.g., Dextrostat, Desoxyn, Adderall, methylphenidate, Ritalin LA, Metadate CD, Concerta, Daytrana, Focalin, etc.). That is, in general, compared to other stimulants tried for ADHD treatment, Vyvanse is equal to or less likely to adversely affect sleep or appetite.

One of my youngest Vyvanse patients has been a 9 year old boy with ADHD, Tourette’s disorder, anxiety disorder, and multiple learning disorders. While his tics were well controlled with Risperdal 3 mg at bedtime, the boy was still inattentive, wiggly, off task, out of his chair, and not completing school work on time – typical ADHD symptoms. We tried Adderall XR (too irritable), Daytrana patch (too inconvenient to apply the patch in the morning), Desoxyn (too expensive), Dexedrine Spansules, and Dextrostat. Both the Dexedrine Spansules and Dextrostat worked well for improving on–task behaviors, but the medications’ duration of benefit was the expected 4–5 hours per dose, and the youngster’s mother didn’t want her son taking any medications at the school (basically, “Just because,” the mother explained). At a Vyvanse dose [carefully and gradually titrated up to an optimal and well–tolerated dose] of 280 mg in the morning, the youngster experienced a dramatic improvement in attention, concentration, and academic performance – without clinically adverse effects on blood pressure, pulse, height, weight; and without a worsening of tics or anxiety.

I recently evaluated and successfully treated a 10 year old boy with ADHD, social anxiety, tics, learning disorders, and PANDAS (pediatric autoimmune disorder associated with strept infections). His tics were under good control with a combination of Risperdal and prophylactic Amoxicillin. For ADHD treatment, he tried Daytrana (associated with a predictable rebound irritability when the patch was removed at the end of the day), and Concerta (– which was too harsh on his appetite). Finally, at a dose [carefully and gradually titrated up to an optimal and well–tolerated dose] of Vyvanse 210 mg in the morning was associated with a dramatic improvement in his classroom performance – without clinically adverse effects on blood pressure, pulse, height, weight; and without a worsening of tics or anxiety. His parents and teachers have been very pleased with the results thus far.

I recently evaluated and treated an 11 year old boy with ADHD, reading disorder, and chronic motor tics. He has previously tried Focalin XR (and didn’t like it). He is doing well with Vyvanse [which was carefully titrated up to the optimal and well–tolerated dose of] 100 mg in the morning.

I recently evaluated and treated a 13 year old girl with ADHD and co–occurring bipolar disorder. Her mood instability and irritability improved with Lithobid 900 mg at bedtime, but inattention, daydreaming, and fidgetiness continued to be interfering with her daily functioning at school, at home, and with her friends.  She tried Concerta (alas, the benefit waned by noon), methylphenidate (alas, the benefit duration was too short to cover the school day), Daytrana (alas, which didn’t work at all), and Strattera (alas, no benefit up to 50 mg daily). She is now doing great at school, at home and with her friends with Lithobid 900 mg at bedtime and Vyvanse [which was carefully titrated up to the optimal dose of] 120 mg in the morning.

I recently evaluated and treated a 13 year old boy with oppositional defiant disorder, ADHD, and an anxiety disorder. He has tried Ritalin LA, and Concerta up to 162 mg in the morning (worked well, but benefit waned at 13 hours after dose). He is doing best he has ever done after switching to Vyvanse [which was carefully titrated up to the optimal and well–tolerated dose of] 100 mg in the morning.

I have treated at least 30 adults over 60 years of age with doses of Vyvanse whose optimal dose ranged from 20 to 280 mg Vyvanse daily. None have had any significant side effects. One of these older Vyvanse–responsive patients is a 61 year–old man whose job requires frequent and prolonged public speaking. Adderall XR, clonidine, Desoxyn, Dextrostat and Focalin XR were effective in managing ADHD symptoms, but all medications caused severe and impairing dry mouth. Concerta was helpful, but its benefit was not dramatic. Daytrana patch was helpful, but the skin reaction from the Daytrana adhesive was irksome. The optimal dose for this 59 year–old professional was Vyvanse [which was carefully titrated up to the optimal dose of] 100 mg in the morning. However, dry mouth at this dose [of 100 mg in the morning] was too bothersome – although the dry mouth was less impairing than other stimulants than he has tried thus far. He continues to report that the benefit from Vyvanse for management of ADHD symptoms at the lower dose of 70 mg in the morning continues to be “good enough for now.” The dry mouth has also decreased over time with this lower Vyvanse dose.‍

Personal Clinical Opinions and Conclusions

Vyvanse is both a new and an old medication. The active ingredient in Vyvanse (i.e., dextroamphetamine) has been prescribed since the early 1900s, and since then, it has been prescribed to millions and millions of children, adolescents and adults for over 80 years now. The time–release formulation which is Vyvanse is new and unique, and the other component of Vyvanse (lysine) is an essential amino acid which has been consumed by humans for thousands of years without problems. Vyvanse is in a new, unique time–release design which results in a more smooth, even benefit for the treatment of ADHD throughout the day, with the benefit continuing for probably 90% or more of ADHD patients until bedtime. Unlike many other stimulants used to treat ADHD, Vyvanse (along with Concerta and Daytrana) enjoys an very low potential for abuse – with the potential for chemical dependence from these medications being lower than that seen from those who drink caffeine daily. Vyvanse is well tolerated, and is in general, much less harsh on appetite than is the case with almost all the other time–release stimulants currently available. Since Vyvanse is the old, familiar dextroamphetamine in a new time–release formulation, there should not be any surprises regarding rare or unusual side effects surfacing from taking prescribed Vyvanse responsibly.

Efficiently switching from another stimulant (i.e., Adderall, Adzenys XR ODT, Desoxyn, Dextrostat, Dexedrine Spansules, Evekeo, Focalin, Ritalin, Metadate CD, Mydayis, Ritalin LA, or Zenzedi) to Vyvanse or vice versa is more challenging than switching between Desoxyn and Ritalin LA because there is not a reliable “conversion formula” for quickly and accurately switching between Vyvanse and the other psychostimulants. Determining optimal Vyvanse (and Daytrana) dose thus will require more “trial and error” efforts than is the case in switching between other stimulants (e.e., switching from methylphenidate to methamphetamine). Nevertheless, in my clinical opinion, I believe that the benefits of Vyvanse are sufficient to justify considering Vyvanse for an empirical trial for those with a legitimate diagnosis of ADHD. A few ADHD patients find Vyvanse 10 mg in the morning the optimal dose for them. Other ADHD patients may need as much as 350mg of Vyvanse in the morning to obtain optimal ADHD symptom management. A computerized continuous performance task test can help to quickly and efficiently identify the optimal Vyvanse dose for any particular ADHD patient.

There are now a sufficient number of published studies and published comprehensive reviews of the literature [e.g., Cooper et al (2011); Faraone et al (2008); Hammerness et al 92011); Pliszka et al (2006), Biederman et al (2005); Olfson et al (2012); Schelleman et al (2011); Wilens et al (2005)] which have conclusively documented the extraordinary safety and efficacy of the stimulants in the treatment of children, adolescent, and adults who have a legitimate diagnosis of ADHD. Insurance or pharmacy benefits managers who attempt to deny pharmacy coverage for Vyvanse (or any of the other stimulants currently used for the treatment of ADHD in children, adolescents and adults) based on some “theoretical” concern about cardiovascular risks of sudden cardiac death from stimulant doses higher than the maximum advertising dose guidelines listed in the Physicians’ Desk Reference can no longer be rationally justified.

Furthermore, as many other internationally–published clinicians have emphasized, ADHD is not a benign condition. When untreated or under-treated, those with ADHD have a very poor prognosis. That is, those with untreated or under–treated ADHD are at an increased life–time risk for: school failure; unplanned adolescent pregnancy; more frequent and more expensive motor vehicle accidents; early–onset substance abuse; divorce (once married, that is); more frequent job changes; bankruptcy; and increased risk of premature death from suicide, homicide, or from a general medical condition.

The only justifiable stance that a medical insurance company can take when it denies pharmacy benefits coverage for Vyvanse – or another medication which is used responsibly in the treatment of those patients with a valid ADHD diagnosis – has to do with the cost of the medication prescribed. That is, a medical insurance company or its sub–contracted pharmacy benefits manager can only legitimately assert something like the following in denying pharmacy benefits coverage for Vyvanse or any other stimulant prescribed to treat ADHD [with my comments in brackets]:

“We are denying coverage of Vyvanse [or another effective medication for the treatment of ADHD] at the dose prescribed for this patient’s potentially–lethal medical condition [i.e., untreated or under-treated, ADHD is a potentially lethal medical condition] because Vyvanse [or another effective medication for the treatment of ADHD] at the dose prescribed is too expensive for our budget, and our CEO only cares about the financial bottom line and his (or her) year–end bonus. Furthermore, do be aware that we really don’t care if, as a consequence of our pharmacy benefits coverage denial for Vyvanse [or another effective medication for the treatment of ADHD] for this ADHD patient ultimately leads to the patient’s premature death. You may appeal this decision but it won’t change our minds. You may pursue legal remedies including filing a complaint with state or federal agencies. We don’t care – this is why our budget for our attorneys’ fees is so large.”

To reiterate: if a medical insurance company or its pharmacy benefits manager denies coverage of Vyvanse or another stimulant responsibly prescribed for the treatment of ADHD, then the above captioned response is the only rationally defensible position that the insurance company or its pharmacy benefits managers can take. Any other response must be construed as disingenuous and self–serving.

I hope that, with time, there will be further clinical trials the results of which will be published to further reassure clinicians, pharmacists, pharmacy benefits managers, state medical boards, patients and parents that Vyvanse when carefully and responsibly prescribed even at doses that are sometimes higher than the current FDA–determined limit for manufacturers’ advertising is just as safe for children, adolescents, and adults with ADHD as are the lower Vyvanse doses. What is paramount for clinicians to remember is that the ADHD patient be prescribed the best dose of Vyvanse (or some other stimulant) in order to obtain optimal control of ADHD symptoms throughout the waking day, and the dose or doses of the stimulant (or stimulants)  that works best for one particular patient varies with what is found to be the optimal stimulant dose for other ADHD patients.

While every stimulant medication in the ADHD armamentarium has it place – and I have patients who preferentially do best on every stimulant preparation currently available for treatment of ADHD – I would not be surprised to see Vyvanse soon become one of the most frequently prescribed medications used in the responsible treatment of attention–deficit/hyperactivity disorder.

Dr. Mortimer is a physician licensed to practice medicine in the State of Washington. He is a diplomate of (i.e., “Board certified” by) the American Board of Psychiatry and Neurology. He is also a fully–trained child & adolescent psychiatrist. Among other things, Dr. Mortimer has been on the clinical teaching faculty for Oregon Health Science University’s Department of Psychiatry, and for the Family Practice Training Program at Eastmoreland Osteopathic Hospital in Milwaukie, Oregon. Dr. Mortimer has served as a principle investigator and as a clinical investigator for phase III clinical drug trials, several of which investigated specific stimulants proposed for the treatment of ADHD. Dr. Mortimer has also seen some of his clinical writings published in peer–reviewed international medical journals. Dr. Mortimer currently enjoys maintaining a full–time, solo private practice in child, adolescent, and general adult psychiatry in the non–incorporated Hazel Dell neighborhood of Vancouver, Washington.

Dr. Mortimer has not received – nor does he expect to receive – any compensation for the time spent in composing and revising this essay on Vyvanse and other stimulants.