How do ADHD medications work?

Like with other areas of psychiatry, we have treatments that work, but we don’t know how for certain.  We have developed theories  based on the evidence available. The main neurotransmitter systems affected by ADHD medications are Dopamine and Norepinephrine.

Dopamine DA and Norepinephrine NE look a lot alike at a molecular level. (In fact, the brain removes one small piece of a DA molecule to make NE.) They are made in different areas of the brain and the roads they take there are different too. Put simply if both the DA and NE circuits are working well, we attend better. By strengthening one, the other, or both, medications decrease the symptoms of ADHD. You can focus more easily (possibly DA primarily), and you can think better about what you are focusing on (possibly NE primarily), if both systems are in good shape.

The heart of this body of theory is that there is a deficiency, particularly of Dopamine, that is corrected by stimulant medication.  Medications that enhance the transmission of Dopamine and/or Norepinephrine thus help improve symptoms. Stimulants like Ritalin and Adderall act by boosting Dopamine “current”.  Stimulants are the most studied and the most used treatments for ADHD.

There are differences in the mechanisms of action of methylphenidate (e.g. Ritalin) and amphetamines (e.g. Adderall), though both are “stimulants“. When one doesn’t work, the other might.

To understand some leading theories of ADHD, think of two common household items, electrical currents and electrical outlets. As a generalization, stimulant medications that help ADHD boost primarily the Dopamine current back to its normal levels so that patients with ADHD can focus, inhibit their motoric hyperactivity and impulsivity, and function normally.

Normal Brain

Dopamine/Norepinephrine Currents

ADHD Brain

Dopamine/Norepinephrine Currents

Treated ADHD Brain

Dopamine Current/Norepinephrine Current

There are also non-stimulant medications available that have demonstrated efficacy for ADHD. These include Strattera, Tricyclic Antidepressants, and Wellbutrin. Some reports of Effexor and other agents being helpful exist as well. These medication primarily boost Norepinephrine current, but also boost Dopamine current as well. Other influences we are learning about include hormones and possibly histamine mechanisms.   Acetycholine, a different neurotransmitter entirely, may play a role as well.

The Horse and Rider

Think of brain functioning as requiring collaboration between two areas of our brains, analogous to the relationship between a horse and its rider. In healthy functioning, our behavior is guided by the rider in our personalities. Sometimes, the horse too frequently breaks free and runs wild at inopportune times.

The circuits or "reins" are between the outer layer of the brain and the region below it AKA the "cortical" and “sub cortical” areas.If you think of the cortex of the brain as analogous to the rider, and the subcortex as analogous to the horse, then in ADHD the reins are not working too well. There is too much horsepower, and too little rider control of it.

In other words, with ADHD, electrical circuits mediated by DA are too weak, analogous to the weakened reigns on a horse. These circuits are important for the horse and rider to yoke together as a cohesive team.

With the circuitry back to normal, the rider can harness his horse successfully and ride off into the sunset.

FOR MOST READERS THIS MAY BE ENOUGH INFORMATION. FOR THE TECHNICALLY INCLINED, PLEASE READ ON FOR MORE INFORMATION.

Electrical currents: In reality, the current is generated by depolarizations of cell membranes that are adjacent to each other. Small packages of neurotransmitters are secreted into the tiny spaces between brain cells (neurons) where it leads to the creation of microscopic currents in adjacent nerve cells. The current thus spreads from one cell to another; a microscopic chain reaction.

Electrical Outlets: Outlets symbolize the post synaptic receptors.

Transporters: Transporters weaken the current by scooping up the DA and NE and putting it back inside nerve cells, i.e. breaking the circuit. ADHD may be caused by genetic mutations in transporters that make them work too much and leave a state of "too little DA".  Stimulants, Strattera and the other agents block transporters.   Strattera boosts NE current mostly, but also increases DA current in what may be a key area, the prefrontal cortex. 

Maybe its not just the transporters. Maybe it’s the receiving nerve cell’s DA receptors, i.e. the outlets, that are broken leading to a weakened circuit. 

Provigil boosts alertness by a different poorly understood mechanism possibly using, in part, Histamine.  There are some reports it can help in ADHD.

Imaging studies are focusing on pinpointing the brain areas that don’t work well. The Dorso Lateral Prefrontal Cortex, and the Dorsal Anterior Cingulate Gyrus are key areas of interest. The Caudate, Putamen, and Globus Pallidus are Sub Cortical areas that are important in regulating hyperactivity, attention and impulse control.

FYI

Long ago, Freud posited that there were two domains of our psyches that are always relating to each other. He called these the id and the ego and used the metaphor of a horse and its rider.