Understand how to naviate the current shortage of pediatric ADHD medications.
Background
Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder most commonly seen in children that may progress into adulthood. ADHD can affect the overall well-being, social interactions, and academic performance of the nearly 6 million children diagnosed with ADHD in the United States as of 2016.1 The subtypes of ADHD include inattention and hyperactivity/impulsivity and can be classified by the Diagnostic and Statistical Manual of Mental Disorders. The first-line treatment should be behavioral therapy, which may include behavioral parent training, behavioral classroom management, or behavioral peer interventions, before moving on to pharmacological treatment. The clinician must take the patient’s past medical history and preferences into consideration when determining an appropriate treatment plan.2 Stimulant medications are considered as first-line pharmacologic therapy in patients older than 6 years.2
These medications have potential adverse drug events (ADEs), such as growth effects, sleep disturbances, and cardiac concerns. Stimulants do have an increased potential for abuse and physical dependence with long-term use and should be used cautiously in patients who are deemed to be at high risk of abuse.2 Another option to treat ADHD is nonstimulant medications. Although nonstimulant medications have been shown to be less effective than stimulant medications, they can be a good alternative for patients who do not want the potential ADEs of stimulant medications, and they have reduced potential for misuse and physical dependence.2
Current shortage
In early August 2023, the Drug Enforcement Administration and FDA released a statement in which they recognized the shortage of prescription stimulants.3 The record-high increase in stimulant medication prescriptions began during the COVID-19 pandemic and may be linked to increased prescribing of medications via telehealth appointments.3 Current stimulant medications that are on national shortage include generic methylphenidate 18-mg, 27-mg, 36-mg, and 54-mg tablets and brand-name Methylin ER 10-mg and 20-mg tablets.4 Many of the generic lisdexamfetamine and both brand-name and generic dextroamphetamine/ amphetamine capsule formulations are also on shortage.4 The initial shortage of dextroamphetamine/amphetamine caused a subsequent increased demand for methylphenidate, which led to its own respective shortage in response.3 An additional reason for these shortages could be a lack of available active ingredients to manufacture the medications.4 This article will continue to discuss medications that are currently available as of January 2024 and may be used as treatment options to mitigate shortages and patient-related concerns (Table).6,9,10,14,16,17,19,20
Discussion
A new dextroamphetamine patch (Xelstrym) was approved in March 2022 for patients aged 6 years and older.5 A clinical study conducted by Cutler et al enrolled patients with ADHD aged 6 to 17 years to receive the transdermal dextroamphetamine patch.ADHD symptoms, as assessed by the Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale, were noted to decrease by an overall least-squares mean difference of −5.87 (95% CI, 6.76 to −4.97; P < .001) when compared with placebo.6
Dextroamphetamine works by blocking the reuptake of dopamine and norepinephrine into the presynaptic neurons, which leads to an increase of monoamines being released into the extraneuronal space.7 Prior to therapy initiation, patients should be screened for a medical or family history of cardiovascular disease and ventricular arrhythmias. The lowest dose of the patch should be used at initiation and titrated weekly based on symptoms to the maximum dose.7 Of note, other stimulants should be discontinued when switching to the dextroamphetamine transdermal patch and only 1 patch should be applied in a 24-hour period.7 The patch should be applied to the upper arm, upper back, chest, hip, or flank 2 hours before the effect is desired and should be removed 9 hours after application.7 The patch may be a good option for patients who struggle taking medication, as the patch may be placed in the morning and left on throughout the school day. Common ADEs include nausea, vomiting, headache, stomach pain, irritability, trouble sleeping, decreased appetite, increased heart rate, increased blood pressure, and muscle twitching, such as tics.7
Lisdexamfetamine dimesylate, the generic version of the stimulant Vyvanse, recently garnered FDA approval in August 2023. The production of the generic product is expected to increase accessibility and lower costs.8 Capsules can be opened and mixed with foods and drinks, such as water, yogurt, and orange juice, until contents have disappeared.9 Lisdexamfetamine dimesylate is contraindicated in patients with hypersensitivity to amphetamine products and those taking monoamine oxidase inhibitors.9 Prior to therapy initiation, patients should be screened for a medical or family history of a cardiac disease, motor/verbal tics, or Tourette syndrome. Similar to other stimulant medications, lisdexamfetamine can increase blood pressure and heart rate.9 Other common ADEs include anxiety, constipation, diarrhea, feeling jittery, dry mouth, weight loss, insomnia, and dizziness.9
Alternative and adjunctive ADHD therapies are available for pediatric patients if stimulant medications are not tolerated or available. Atomoxetine (Strattera) is a nonstimulant that is FDA approved for use in children aged 6 years and older to treat ADHD and works through selectively inhibiting the presynaptic norepinephrine transporter.10 Atomoxetine offers weight-based dosing, which may be an advantage specifically in the pediatric population. However, children must be able to swallow the capsules whole as they cannot be chewed, crushed, or opened.10 Atomoxetine can be taken once daily or divided twice daily, pending patient and caregiver preference, and should be trialed for at least 4 weeks to see full clinical benefit.10,11 Dose adjustments should be made in patients known to be poor metabolizers of cytochrome P450 2D6.12 ADEs include abdominal pain, nausea, vomiting, behavioral changes, decreased appetite, risk of liver damage, pediatric priapism, and auditory hallucinations.11,13 Atomoxetine carries a black box warning for suicidal ideation and is associated with delayed growth development.2,10,11 Atomoxetine is a feasible alternative, but parents should be made aware that nonstimulant medications have a lesser effect on ADHD than stimulants.2
Another nonstimulant medication, viloxazine (Qelbree), was approved in April 2021 for children aged 6 years and older. Viloxazine is available as an extended-release capsule that is administered once daily.14 The capsule may be opened and sprinkled on foods, making it a feasible therapeutic option in children with an inability to swallow medications.15,16 This medication works through blocking norepinephrine reuptake and increasing serotonin levels in the prefrontal cortex.15 When compared with atomoxetine by Price et al,12 viloxazine had demonstrated a greater change from baseline in the pediatric ADHD Rating Scale-5 in 35 children who each received a 4-week trial of both atomoxetine and viloxazine (t = − 10.12; P < .00001). A total of 89% of the children within the study had a reported positive response by 2 weeks of therapy with viloxazine compared with 14% with atomoxetine.16 Tolerability was also noted to be higher in the viloxazine treatment period, as only 4% of the total patient cohort discontinued viloxazine due to ADEs vs 36% of patients during the atomoxetine treatment period.16 Viloxazine can be used concomitantly with other stimulants and can be initiated on the titration schedule if switching from a stimulant.17 Common ADEs of viloxazine include fatigue, weight loss, insomnia, upper respiratory infections, and abdominal pain in children and adolescents. There also is a black box warning for suicidal ideation and behavior.16
Guanfacine and clonidine are approved as add-on therapy to stimulants for the treatment of ADHD and work via central alpha-2A adrenergic receptor agonists.16,17 Intuniv, the brand name for extended-release guanfacine, can be initiated after lack of response in a 6-week stimulant trial. Similar to atomoxetine, the tablet must be taken whole.16 Patients may experience somnolence, fatigue, nausea, lethargy, insomnia, and abdominal pain. If the medication needs to be discontinued, the dose should be tapered down every 3 to 7 days.17 Extended release clonidine (Kapvay) is given at bedtime due to its sedating potential.17 It is important to note that the immediate-release and extended-release clonidine are not interchangeable on a milligram-per-milligram basis due to differing pharmacokinetic profiles.17,18 Doses may be increased weekly as clinically necessary.19 The daily dose can be divided to twice daily as the dose increases with titration; however, if the daily dose is split unevenly, the larger dose should be given at bedtime.17 Similar to guanfacine, the dose should be tapered every 3 to 7 days upon discontinuation.17 ADEs of clonidine include somnolence, fatigue, upper respiratory tract infection, irritability, sore throat, insomnia, and emotional imbalance.17
Conclusion
As listed prior, the medications mostly affected by the national shortages are the generic formulations of the stimulant treatment options. However, the medications in this article are currently available for patient use and should be considered if a patient’s typical medication is on shortage. If planning to switch between stimulants, clinicians should refer to available conversion references and remember that several medications, such as dextroamphetamine and amphetamine salts, are not equivalent on a milligram-per-milligram basis.21-23 Other potential remedies include prescribing specifically for the brand formulation of the medication on shortage with the denotation to not substitute; although insurances may not cover brand formulations. Pharmacists can play a vital role by helping patients obtain medication access through available manufacturer discount cards and patient assistance programs. If switching to a different medication is not feasible, another potential remedy clinicians could offer is to employ weekend medication holidays for the patient. A study by Martins et al did not demonstrate an increase in ADHD symptoms when employing a methylphenidate weekend holiday vs standard daily dosing in a cohort of 40 children.24
Education of the ongoing shortages and knowledge of other treatment options is imperative to optimize a patient’s treatment regimens and quality of life. Although certain medications continue to be unavailable, providers should ensure patients that effective and safe alternatives can be used to treat the symptoms of ADHD. These alternative treatment options may also be explored due to caregiver’s preference, patient tolerability issues, lack of medication benefits, and other unmanaged psychiatric comorbidities.
References:
Overcoming pediatric obesity: Behavioral strategies and GLP-1 support
October 4th 2024Kay Rhee, MD, discusses the challenges of pediatric obesity treatment, highlighting the role of biological and environmental factors, behavioral interventions, and the potential benefits of GLP-1 medications in weight management for children and teens.
Socioeconomic and racial disparities found in pediatric opioid prescriptions
September 29th 2024A study presented at the 2024 AAP Conference found that white children and those from higher socioeconomic backgrounds are more likely to receive opioid prescriptions for fractures. Despite effective non-opioid alternatives, disparities persist in opioid prescription patterns.
Overcoming pediatric obesity: Behavioral strategies and GLP-1 support
October 4th 2024Kay Rhee, MD, discusses the challenges of pediatric obesity treatment, highlighting the role of biological and environmental factors, behavioral interventions, and the potential benefits of GLP-1 medications in weight management for children and teens.
Socioeconomic and racial disparities found in pediatric opioid prescriptions
September 29th 2024A study presented at the 2024 AAP Conference found that white children and those from higher socioeconomic backgrounds are more likely to receive opioid prescriptions for fractures. Despite effective non-opioid alternatives, disparities persist in opioid prescription patterns.
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