I can’t resist adding some extra ideas to Dr. Plyler’s review of Amy Arnsten’s article, Catecholamine Influences on Dorsolateral Prefrontal Networks 1. As he indicated, ADHD is one of the conditions on which we focus in this practice. Dr. Arnsten’s paper made several points that deserve special emphasis.
- The neurochemical control of the DLPFC (that part of the frontal cortex mediating control of attention, response inhibition, and working memory – the neuropsychological capacities whose impairment generates the classic symptoms of ADHD) under normal conditions is exquisitely calibrated to environmental demands and internal reserves. Put differently, the regulatory actions of our DLPFC are adjusted on an almost second to second basis, depending on the immediate cognitive tasks confronting us and our level of stress and fatigue. This dynamic reality contrasts with the more popular but almost cartoonish view of certain brain regions monolithically carrying out set functions.
- With this understanding of how the brain (the DLPFC in particular) operates under normal circumstances, a realization is inevitable: our pharmacotherapeutic efforts at treating ADHD are laughably clumsy and primitive by comparison. In contrast to the immediate neurochemical changes that cause fine-grained temporal adjustments in DLPFC functioning, our use of medication is bulky and nonspecific. We do not have the capacity to alter our medications on a second to second basis, nor make quick adjustments in doses depending on the particular challenges facing the individual. This realization should humble all of us engaged in the therapy of this challenging disorder. We need a brain-based version of the insulin pump: a delivery method that can more finely titrate dosing according to environmental demands.
- This realization has a practical implication for the pharmacotherapy of ADHD: Customize! We should tailor our medication efforts to the specifics of each patient’s daily needs and the variability of their needs. For those with regular daily schedules such as full-time businessmen, stay-at-home moms, or college students, using set doses of long acting stimulants may be the easiest and most effective treatment strategy. For those with more erratic schedules though, such as part-time students, project-based workers, or parents whose demands ramp up in the morning and the evenings when their kids are home – these patients may benefit from more flexible dosing strategies of their stimulants. They may also benefit from shorter-acting agents that allow greater therapeutic fine-tuning. Whichever route is optimal, it should be carefully worked out together as part of the treatment process.
- Last, ADHD is not only about dopamine. Arnsten emphasizes the critical and overlooked role of norepinephrine in DLPFC function and impairment. This leads to a second clinical implication: Don’t forget about noradrenergic agents in treating ADHD. Yes, stimulants will hit both dopamine and norepinephrine, but for those who cannot tolerate or those who fail to respond optimally to these agents, we must give more serious consideration to atomoxetine and guanfacine. In our experience, these noradrenergic medications are under-utilized.