There is little agreement on how high to dose stimulants. One common rule of thumb is to prescribe 1 mg/kg body weight of methylphenidate (MPH) vs. 0.5 mg/kg of amphetamine (AMP) preparations (Sachdev P et al., Aust N Z J Psychiatry 2000;34(4):645- 50). Using this for the average 12-year-old boy (50th percentile is 40 kg, or about 90 pounds), Ritalin (MPH) would be dosed at 40 mg/day and Adderall (AMP) at 20 mg/day. The average adult male weight is about 75 kg or 165 lbs, meaning the weight-based dose of Ritalin is 75 mg/day or 37.5 mg/day of Adderall.
If we follow this logic, though, we run afoul of the FDA, since the maximum recommended dose of almost all stimulants is 60 mg. The fact is that many patients need much higher than recommended doses, especially adult patients. Maximum recommended doses are arrived at based on initial clinical trials by drug companies. Companies will typically err on the side of caution and choose as the maximum tested dose a relatively low one to prevent side effects and maximize the chances of FDA approval. But in the real world, many patients may need higher doses.
Generally, when patients are dosed according to algorithms that specify increases in doses when response is suboptimal, patients are given doses higher than those given in community settings. For example, in the NIMH-sponsored Multimodal Treatment Study of Children With ADHD (known as the MTA) 579 children with ADHD were randomly assigned to four treatment groups: medication management, med management combined with behavioral therapy, behavioral therapy alone, and community care (in which patients received care of their choosing, often from a pediatrician).
The average final dose of Ritalin in the community care patients was 18.7 mg/day, whereas patients assigned to researcher-clinicians received an average of 32.8 mg/day. The patients on the higher doses improved more (Jensen PS, et al., J Dev Behav Pediatr 2001;22:60-73).
The MTA study used a “forced titration” strategy. This meant that at monthly visits symptoms were rated with the Clinical Global Improvement scale. If patients had ADHD residual symptoms (or if they had significant side effects), the algorithm required a specific change—an increase in dose for residual symptoms or a decrease or switch to another drug in cases of side effects. This active approach to dose titration was designed to rapidly lead to a state in which there was “no room for improvement” within the dosing limits set by the study and FDA, using the terminology of the authors (Vitiello B et al., J Am Acad Child Adol Psychiat 2001;40(2):188-196).
Studies have shown that community doctors tend to underdose adults with ADHD as well. In one survey, average dosing in the community was 30 to 40 mg/day of Concerta and 30 mg/day of Adderall XR. Compare these paltry doses to what clinical trials have found is most effective in adults: Concerta 80 mg/day and Adderall XR 60 mg/day (Olfson M et al., J Clin Psychopharm 2008;28(2): 255-257).
Meanwhile, anecdotal reports indicate that some patients, particularly adults who are overweight, require much higher doses. For example, Marc Schwartz and Nicholas Schwartz carried out a study of optimal stimulant dosing in their private practice and published the results on their website, www.adult add.info. After reviewing the charts of 260 adult ADHD patients, they found that the average optimal daily doses were 67 mg/day for MPH, 53 mg/day for AMP, and 83 mg/day for Vyvanse (lisdexamfetamine), the newest stimulant. The maximum dose was more than 200 mg/day for all stimulants. These results have not been subject to the peer review process, but they are intriguing nonetheless—especially with their finding that Vyvanse requires significantly higher dosing (about 1.5 times higher) to have the same effect as its competitors.
Preventing stimulant abuse and diversion
All stimulants are controlled substances, meaning that they are classified by the Drug Enforcement Administration (DEA) as schedule II, a category they share with other highly abusable drugs such as methadone and oxycodone. Such drugs cannot be refilled and can not be called into the pharmacy. This means that we have to require law-abiding citizens with genuine ADHD to come pick up a paper prescription every month, a chore for many patients. However, two years ago, on December 19, 2007, the DEA changed its rules to officially sanction a procedure common in medicine—namely, writing multiple sequential prescriptions of stimulants, up to a maximum of a 90-day supply. (You can read the final rule at http://bit.ly/5lVgBp.)
The new guidelines, however, do not allow you to actually “post-date” prescriptions. To designate prescriptions to be filled later, you must write the instructions for the pharmacist in the body of the prescription using wording such as “Do not fill before [date].” Thus, for example, if I see a patient on 1/1/2010, I could write out three sequential prescriptions of stimulants. All three would be dated “1/1/2010.” In the body of the first month’s script, I would simply write in the medication dose and instructions— no different from any standard prescription. In the second month’s script, somewhere below today’s date, I would add “do not fill before 2/1/2010,” and on the third month’s script I would write “do not fill before 3/1/2010.” Not all states have to agree with this federal ruling, and in states where the controlled substance laws are more restrictive, you may not be able to take advantage of the DEA’s new policy.
While the majority of patients do not abuse or divert their stimulants, every practice has a few who do. The red flag of stimulant abuse is when patients tell you that they need to fill a prescription early. Typical reasons given are that the prescription was lost, was dropped into the sink, was stolen by a friend of the family, that the patient is going on a long trip and needs extra, etc. How to handle this will vary depending on your level of trust of the patient. A common strategy is to allow patients only one extra refill and to document that you informed them of this policy. Another technique is to tell all your patients on stimulants ahead of time that you will write no more that one prescription per month and will never make any exception.
Some completely innocent patients will complain, but unfortunately we have no way of knowing whether patients are being truthful or not. If a patient says: “Why don’t you trust me?” you can respond with some variant of, “I trust you, but it’s the drugs I don’t trust. I’ve seen too many patients get addicted to them, often with the best of intentions, and getting addicted to stimulants can cause too much damage to your life.” You can also point out to patients that there is no dangerous withdrawal syndrome from stimulants—the worst that is likely to happen is some fatigue for a few days, and, of course, a return of the symptoms of inattention for which they are presumably being prescribed the medication.
The potential downside of this strict policy is that honest patients will be penalized for the unethical behavior of others. After all, patients with ADHD are by definition absent-minded and are particularly likely to misplace their scripts. In general, diversion of stimulants is more likely in adolescents (who might give or sell the drugs to classmates) and in lower income patients, who might need the money derived from selling prescription meds. Follow your instincts—if the patient is trustworthy, the reason for the early refill is believable, and the situation is documented in the chart, dispensing extra medication is defensible and will not get you into trouble with the DEA.