Explaining the Cognitive-Enhancing Effects of ADHD Treatments

Explaining the Cognitive-Enhancing Effects of ADHD Treatments

August 4, 2008

Norman Sussman, MD, DFAPA

Editor, Primary Psychiatry and Psychiatry Weekly, Professor of
Psychiatry, New York University School of Medicine

First published in Psychiatry Weekly, Volume 3, Issue 27, on August 4,
2008

The clinical use of psychostimulants to treat
attention-deficit/hyperactivity disorder (ADHD) is widespread, but the
neural mechanisms responsible for their
cognition-enhancing/behavioral-calming have never been adequately
explained. This lack of clarity makes it more difficult to address
criticisms that these drugs are not effective or are harmful.

The fact is that stimulants are high on the list of controversial
psychotropic medications. Apart from unanswered questions about how
these drugs work, a major reason for concern about the use of drugs like
amphetamines and methylphenidate is that they have a potential for
diversion for recreational use, or some argue, may result in abuse among
those who use them therapeutically. Most recently, there have been
reports that influential researchers at Harvard Medical School may not
have adequately disclosed the extent of their relationships with
manufacturers of ADHD medications; these reports have raised additional
questions about the validity of some studies that show very favorable
risk-benefit profiles when these drugs are used to treat ADHD.1

Understanding how a drug works-demystifying its mechanism of action-can
go a long way in overcoming excessive skepticism or antipathy to a
psychotropic agent. It can also help in the development of more
effective or better-tolerated medications. It may be helpful that
researchers have made recent progress in explaining how these drugs
work.

Devilbiss and Berridge2 report that methyphenidate "fine-tunes" neuronal
activity in the prefrontal cortex. This is the brain region involved in
attention, decision-making, and impulse control. Of particular interest
is that the medication had little or no effects on other areas of the
brain. To investigate, Devilbiss and Berridge2 attached tiny electrodes
to individual neurons in the brains of normal rats and watched how
different doses of the drug affected neuron activity. This is an
important study because it seeks a more scientific explanation for the
cognition-enhancing/behavioral-calming actions of these drugs.

The usual response to the question of "How do these drugs work?" has
been to say that they raise brain activity of the catecholamine
neurotransmitters, dopamine and norepinephrine. This study2 provides a
more complex but more specific explanation. According to the authors,
the study showed that cognition-enhancing doses of methylphenidate
"increase the magnitude of both excitatory and inhibitory responses of
pre-frontal cortex [PFC] neurons while simultaneously reducing the
duration of the inhibitory response. Low-dose methylphenidate also
produced 'gating,' resulting in a larger number of PFC neurons
responsive to CA1-subiculum input. Combined, these observations suggest
that low-dose methylphenidate increases both the sensitivity of PFC
neurons and the pool of responsive PFC neurons in a more complex manner
than simply regulating the level of PFC excitability (ie, gain of
neuronal activity), consistent with known actions of catecholamines on
cortical neurons."

As we learn more about the underlying neurobiology of ADHD and the
mechanism-of-action of drugs that treat it manifestations, the idea of
seeking treatment will become more prevalent and the types of treatment
options will expand.

References

1. Harris G, Carey B. Researchers fail to reveal full drug pay. New York
Times. June 8, 2008. Available at:
www.nytimes.com/2008/06/08/us/08conflict.html. Accessed July 21, 2008.

2. Devilbiss DM, Berridge CW. Cognition-enhancing doses of
methylphenidate preferentially increase prefrontal cortex neuronal
responsiveness. Biol Psychiatry. 2008 Jun 26. [Epub ahead of print].

Disclosure: Dr. Sussman reports no affiliations with, or financial
interests in, any organization that may pose a conflict of interest.

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