Prescribing and Dosing Stimulants

[Chip (OP)]

source: https://psychcentral.com/pro/prescribing-and-dosing-stimulants-practical-issues#1

Prescribing and Dosing Stimulants: Practical Issues

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 changean 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.