Guanfacine (Tenex) and working memory

#1 takes both Ritalin and Guanfacine (Tenex and other trade names) - longterm. So I track research on both meds.

Ritalin is as well understood as any brain med. As best we can tell it's unreasonably safe and effective for ADHD, despite a trashy article in a pop science magazine.

Guanfacine, a second line med for ADHD also used (off label) for "explosive" kids, is much less studied than Ritalin. The proposed mechanisms of action are interesting, it seems to increase certain kinds of neuronal connections and to perhaps facilitate learning capabilities.

On the one hand, this is encouraging. Working memory deficits are a significant component of most developmental disorders of the brain. On the other, it's disturbing. When clinicians hear "increased cellular activity" in brains we think "cancer" and "seizure".

Fortunately, so far, there's no sign of that (though we're in early days). There is, however, continued research on Guanfacine's effect on working memory and task performance in primates. Studies have recently moved to using elderly primates, but results are mixed. As best I can tell from the abstract, this was a negative result (A typical child dose of Guanfacine would be .04 mg/kg) ...

Effects of the alpha-2 adrenoceptor agonist g... [Eur J Neurosci. 2011] - PubMed - NCBI

Alpha-2 adrenergic receptors are potential targets for ameliorating cognitive deficits associated with aging as well as certain pathologies such as attention deficit disorder, schizophrenia and Parkinson's disease. Although the alpha-2 agonist guanfacine has been reported to improve working memory in aged primates, it has been difficult to assess the extent to which these improvements may be related to drug effects on attention and/or memory processes involved in task performance. The present study investigated effects of guanfacine on specific attention and memory tasks in aged monkeys.

Four Rhesus monkeys (18-21 years old) performed a sustained attention (continuous performance) task and spatial working memory task (self-ordered spatial search) that has minimal demands on attention. Effects of a low (0.0015 mg/kg) and high (0.5 mg/kg) dose of gunafacine were examined. Low-dose guanfacine improved performance on the attention task [i.e. decreased omission errors by 50.8 ± 4.3% (P = 0.001) without an effect on commission errors] but failed to improve performance on the spatial working memory task. The high dose of guanfacine had no effects on either task. Guanfacine may have a preferential effect on some aspects of attention in normal aged monkeys and in doing so may also improve performance on other tasks, including some working memory tasks that have relatively high attention demands.

The doses are interesting here -- much lower than a human therapeutic dose and much higher. They were also looking at a one time dose effect. This reads like a mini-pub as a research team gears up for the real research. It's a modest investigation, and they basically didn't find anything. (Give the cost and ethics of primate experimentation one assumes there's much more to come.)

So the results are pretty meaningless. What's interesting is that the research is gearing up.

We should learn a lot more about the risks and benefits of Guanfacine over the next five years. For now I'm comfortable with our son's use of this medication.