Taking the stress out of individualizing ADHD drug therapy

Case

Fred is a 9-year-old boy who has been your patient since he was born. Last year, after failing the fourth grade, Fred was diagnosed with ADHD, inattentive subtype. Over the past year, Fred’s ADHD symptoms have responded extremely well to methylphenidate (MPH). His dose was titrated to optimize control of his symptoms, and his current dosage is 10 mg, 3 times daily (8 am, noon, and 4 pm). He receives his morning and late-afternoon doses at home, and his noon dose is administered at school by the school nurse. He is doing much better academically, has developed many good friends, and has had no problems tolerating the medication so far. He has a healthy appetite, is an average weight and height for his age, and sleeps well at night. Fred’s parents also believe that the behavioural therapy training workshops they attended have improved their ability to understand Fred’s behaviour and provide more structure in his home environment.

Fred will soon be moving to a new school that has a policy that prevents school personnel from administering MPH or other medications. Fred’s parents are concerned that Fred will forget to take his noon dose at school. They come to see you at the clinic to discuss the possibility of changing Fred to one of the newer ADHD medications that will work for the whole school day. They also ask if they need to worry about warnings they have read about ADHD medications causing “problems with the heart.”

In an effort to enhance the individualized approach to ADHD management, and to ultimately improve tolerability and adherence to therapy, an increasing number of products with novel delivery systems have become available in Canada. Table 13,9,17,18 lists available products and differentiates them according to whether they are short-acting, intermediate-acting, or long-acting preparations. Generally, all psychostimulants are considered equally efficacious and they do not differ considerably with respect to tolerability.9 The differences among the psychostimulant delivery systems often guide prescribers’ choices. These differences relate to onset of action, duration of effect, cost, convenience of administration, and dosage form (capsules that can be opened vs tablets that must be swallowed whole).

While short-acting agents are less expensive, are more easily titrated, and can be timed to correspond to certain activities (eg, homework in the evening), long-acting medications also offer advantages. Sustained-release MPH and Dexedrine Spansules, although slightly longer acting than immediate-release (IR) formulations, often require multiple daily dosing (therefore administration at school is necessary) and might be combined with IR tablets for faster onset. These regimens tend to be complicated to adhere to and result in the child having to carry medication to schools or care facilities, increasing risk of drug diversion and theft. Once-daily psycho-stimulant preparations, while more expensive, might improve adherence to therapy and decrease abuse and diversion risk. Once-daily preparations not only obviate the need for doses during the school day, but have also been shown to be as effective as MPH administered 3 times daily12 and are less likely to be abused owing to barriers within their formulations. Physicians might also want to consider using treatment agreements* as part of the patient education process to decrease abuse and diversion risk. The RxFiles ADHD newsletter, available on CFPlus,* offers other strategies to reduce stimulant abuse and diversion risk. Once-daily administration allows for a 10- to 12-hour duration of effect, which essentially provides therapeutic drug levels throughout the entire school day and into the early evening. This is important for after-school peer and parent interactions and also for completing homework tasks. Additionally, long-acting stimulants might result in less rebound hyperactivity.

For the purposes of promoting adherence to therapy and maintaining his therapeutic gain, it is reasonable to consider converting Fred’s current regimen of thrice daily MPH IR to a once-daily preparation, although this might have cost implications. As he has responded adequately to MPH without side effects, it is reasonable to convert him to a once-daily MPH preparation or alternate psychostimulant (eg, extended-release Adderall). The dosage conversion from an IR product to a long-acting preparation or another dosage form of the same drug is not necessarily 1 to 1.9,10 For example, Fred’s 10-mg dose of MPH 3 times daily might be converted to a 27-mg or 36-mg dose of Concerta once daily. Alternatively, he could be switched to Biphentin, 20 or 30 mg daily.

Some individuals respond to or tolerate one formulation of stimulant differently than another. Furthermore, dosage conversions are only approximations and need to be individualized. It is essential to closely monitor patients for both effectiveness of the drug and any adverse effects. Therefore, during the dose-titration process it is useful to have information about Fred’s progress from multiple sources, including his teachers. Regular documentation (every few months) of ADHD symptoms and impairment should be made through the appropriate use of rating scales, such as SNAP-IV (Swanson, Nolan and Pelham Teacher and Parent Rating Scale)19 and CGI (Clinical Global Impression scale),20 and also based on academic performance. The Canadian Attention Deficit Hyperactivity Disorder Resource Alliance website (www.caddra.ca) contains links to scales and other useful monitoring tools. Management of side effects will depend on their severity. Mild appetite suppression and insomnia are usually expected and tolerable. Moderate to severe side effects warrant reduction of the dose, discontinuation of the medication, introduction of a different formulation, or use of adjunctive treatments. Box 110,21,22 offers ideas on individualizing therapy. The RxFiles newsletter* provides a more comprehensive list of comorbidities and side effects and further information on their management.

Some patients might require a small dose of additional MPH IR in the late afternoon or early evening to control evening symptoms for activities such as school events, homework, and family functions.9 Alternatively, the 22% of drug released immediately from Concerta might not be sufficient to manage morning symptoms in some patients. In such instances, morning supplementation with MPH IR or a change to another long-acting formulation with a higher percentage of drug released immediately (eg, 40% with Biphentin or 50% with extended-release Adderall) might be beneficial.

Concerns have been raised regarding use of psycho-stimulants and the possible, rare association with cardiac events and sudden death.23,24 There is inadequate evidence to establish a causal relationship; however, patients with known cardiac structural or rhythm abnormalities or signs and symptoms suggestive of cardiac disease should not be prescribed these drugs.25 Whether a routine electrocardiogram (ECG) is necessary has been open to debate.25,26 An ECG increases the likelihood of identifying serious cardiac conditions, especially if there are suspicions of high-risk conditions; ECGs should be read by physicians with expertise in reading pediatric ECGs. Pediatric cardiology should be consulted if there are serious cardiac findings, abnormal ECG results, or family history of sudden cardiac death in relatives younger than 35 years of age.25

In some patients, a “drug holiday” might be considered during school breaks or summer holidays to assess the level of ADHD symptoms while not taking therapy and reassess the clinical need for medication. Decisions regarding drug holidays must be made on a case-by-case basis. In addition, the patient, parents, and physician should review the goals of therapy every 2 years.

Conclusion

This case illustrates that psychostimulants administered once daily in a long-acting formulation can offer some advantages, particularly in school-aged children. However, as with all medication, adherence to ADHD medication regimens can decrease over time. It is essential, therefore, that strategies are employed to improve adherence. Other strategies that have been effective for improving adherence included the following14:

• Educate patients and parents about anticipated results, benefits, and possible adverse effects.

• Provide frequent follow-up early in treatment, especially during dose titration.

• Strive for dose optimization.

• Identify and treat comorbid conditions.