The article was medically reviewed by Dr. Pavlo Papach, a psychiatrist at Maale Hacarmel Mental Health Center in Israel. All the information is offered for educational purposes only.
The ADHD brain works somewhat differently from a neurotypical brain. ADHD medications aim to ameliorate some of these divergent patterns of brain activity by balancing specific brain systems. Getting a handle on ADHD medication requires some neuroscientific knowledge, so prepare for a quick neuroanatomy tutorial.
The neuroanatomy of the ADHD brain
The symptoms of ADHD are thought to arise from specific neurochemical changes in the circuits that involve the frontmost part of the brain called the prefrontal cortex, namely:
Dorsolateral prefrontal cortex (DLPFC) is linked to inattention
Dorsal anterior cingulate cortex (dACC) - to difficulties with focusing
Orbitofrontal cortex (OFC) - impulsivity
Supplementary motor area (SMA) - restlessness and excessive movement.
The image below highlights the areas of the prefrontal cortex involved in ADHD:
Prefrontal cortex activity in ADHD is thought to be caused by the dysregulation of two neurotransmitters: dopamine and norepinephrine. Both of these brain chemicals play a crucial role in making neural connections in the prefrontal cortex, including cognitive functions affected in ADHD, such as attention, motivation, and movement.
The natural question is, does ADHD occur when NE (norepinephrine) and DA (dopamine) in the prefrontal cortex are too low or too high? “The answer seems to be that either too much or too little stimulation by NE or DA can cause inefficient information processing because for the prefrontal cortex to work [...], cortical pyramidal neurons need to be tuned, […] neither too high nor too low,” writes Prof. Stephen M. Stahl, author, and professor of psychiatry at the University of California, San Diego, in Stahl’s Essential Psychopharmacology.
When the activity of norepinephrine and dopamine receptors is too low, all incoming neural signals are perceived as the same, giving rise to unguided attention (when a person has trouble focusing on a task). If stimulation is too high, neural signals get scrambled, which also affects a person’s attention.
The challenge of getting norepinephrine and dopamine levels just right explains why a wide range of ADHD medications and doses may be required for various people.
How ADHD medication works
Psychostimulant medications are the primary way to reduce ADHD symptoms. But the name ‘stimulant’ is itself misleading. The National Institute of Mental Health explains: “Although it may seem unusual to treat ADHD with a medication that is considered a stimulant, it works by increasing the brain chemicals dopamine and norepinephrine, which play essential roles in thinking and attention.”
Stimulants are divided into two distinct types: those based on methylphenidate and amphetamine. Both of them increase the levels of norepinephrine and dopamine in the prefrontal cortex, and they do so in similar ways.
Each nerve cell, or neuron, produces neurotransmitters to communicate with neighboring neurons. Once communication has taken place, the neuron reabsorbs the neurotransmitters in a process called reuptake. Stimulant medications like methylphenidate and amphetamine prevent the reuptake of dopamine and norepinephrine to make more of these two neurotransmitters readily available. This way, stimulants improve the connection between nerve cells and the functioning of brain areas with imbalanced connectivity, such as the DLPFC.
The difference between methylphenidate and amphetamine lies in the extent to which they influence these two systems.
Both methylphenidate and amphetamine are classified as Schedule II Controlled Substances. However, ADHD treatment doses are much lower than those that can lead to dependence.
Non-stimulant ADHD medications
Non-stimulants target a variety of brain pathways. Unlike stimulants, these ADHD medications don’t improve neurotransmission by directly influencing dopamine and norepinephrine. Instead, they either block the reuptake of norepinephrine alone or involve other neurotransmitters altogether. These medications are prescription only, but they’re not considered controlled substances.
Medications like atomoxetine (Strattera) and viloxazine (Qelbree) prevent the reuptake of norepinephrine. Due to a limited effect on dopamine, these medications are not primary treatments for ADHD, even though they are equally capable of improving attention, hyperactivity, and impulsivity.
Two other medications – guanfacine and clonidine – are sometimes used to improve insomnia and excessive activity in children with ADHD. These medications also improve attention, even though they don’t directly influence dopamine or norepinephrine. Clonidine and guanfacine target a type of adrenergic receptor that partially substitute for norepinephrine.
Lastly, some but not all antidepressants, such as bupropion (Wellbutrin) and venlafaxine (Effexor), improve ADHD symptoms. Like atomoxetine, these antidepressants influence norepinephrine.
What can one expect when ADHD medication works?
Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD) point out that medication is meant to target the core symptoms of ADHD, namely inattention, hyperactivity, and impulsivity, rather than change one’s behavior. “Medication, which can only be prescribed by medical professionals, is used to improve the symptoms of ADHD so that the individual can function more effectively,” states the organization.
As per Additude Magazine, medications should translate into:
Sustained focus: the person is able to concentrate for a longer time and direct attention better than before
More attention to detail
Higher productivity may result in less stress or anxiety.
There is a wide range of effects that medications can have on individuals. Some people experience profound benefits, others find medication to be helpful but not groundbreaking, and others still only experience limited benefits. A combination of medication and other therapeutic approaches, such as coaching and psychotherapy, is recommended for optimal results.