Case Study 6: When a Stimulant Improved Focus but Made Behaviour Much Worse

Reason to come to PPI: The ADHD medication helped attention—but anxiety, insomnia and agitation became overwhelming.

A young patient with ADHD had been prescribed a stimulant medication, including an amphetamine-based treatment. At first, there was a clear benefit.

The patient became:

• More focused
• More attentive
• Better able to concentrate But at the same time, other symptoms became much worse.

The patient experienced:

• Anxiety
• Insomnia
• Agitation
• Impulsivity
• Erratic behaviour The problem became so serious that the patient’s mother was concerned that the child would soon be unable to remain in school.

The medication was helping attention, but overall, the patient was functioning worse.

This raised an important question: Why would a medication improve focus while making behaviour and emotional control worse?

PPI Looked at Dopamine and Norepinephrine

The two brain chemicals most closely involved in ADHD treatment are:

• Dopamine

• Norepinephrine These chemicals help regulate:

• Attention

• Concentration

• Motivation

• Working memory

• Impulse control

• Alertness PPI’s assessment suggested that the patient had a slightly reduced functional tendency in dopamine and norepinephrine-related systems.

This helped explain why a stimulant could improve attention. But it did not explain why the patient became so overstimulated. So, PPI looked deeper.

How Amphetamines Work

Amphetamine-based stimulants have a strong effect on both:

• Dopamine
• Norepinephrine Rather than simply slowing their removal, amphetamines also increase their release from nerve cells.

A simple way to think about it is:

1. Amphetamine
2. More dopamine and norepinephrine are released
3. Attention and alertness can improve

For many people with ADHD, this is helpful.

But if the increase becomes too strong for that patient:

1. Dopamine and norepinephrine rise too quickly or too strongly
2. The brain can become overstimulated

This may appear as:

• Anxiety
• Restlessness
• Difficulty sleeping
• Irritability
• Agitation
• Emotional reactivity
• Increased impulsive behaviour

COMT Provided an Important Clue

PPI then examined genes involved in clearing dopamine and norepinephrine.

The patient had:

• Normal MAOA activity
• Normal MAOB activity

Lower COMT activity

COMT is an enzyme that helps remove dopamine and norepinephrine, particularly in the Prefrontal cortex, the part of the brain responsible for:

• Attention
• Planning
• Working memory
• Behavioural control
• Decision-making A simple way to think about COMT is COMT helps clean up dopamine after it has been used.

If COMT activity is lower:

1. Dopamine is released
2. It may be cleared more slowly in certain brain circuits
3. Dopamine signaling may remain stronger for longer

Why Was This Important?

The patient’s overall profile suggested that dopamine and norepinephrine functioning might be slightly reduced, but probably not profoundly low.

The normal MAOA and MAOB findings, together with lower COMT activity, suggested that the patient might still have a reasonable ability to maintain catecholamine signaling. Then a strong releasing medication was added Amphetamine

A simplified picture was:

1. Some need for dopamine/norepinephrine support
2. Amphetamine strongly increases both chemicals
3. Lower COMT activity may make dopamine slower to clear in the prefrontal cortex
4. The treatment may overshoot the patient's optimal range

The result may have been better focus but too much activation.

ADHD Medication Is About Finding the Right Range

More dopamine and norepinephrine are not always better. The brain works best within a range.

Too little may contribute to:

• Poor attention

• Low motivation

• Distractibility Too much may contribute to:

• Anxiety

• Agitation

• Insomnia

• Impulsivity

• Emotional instability For this patient, the stimulant appeared to move attention in the right direction but pushed overall activation too far.

What About Serotonin?

The patient’s anxiety, agitation and impulsivity also suggested that emotional-control systems were not adequately supported.

Serotonin helps regulate:

• Anxiety
• Emotional stability
• Impulse control
• Irritability
• Stress responses It would be too simple to say that amphetamine automatically “lowered serotonin.” The relationship between stimulant treatment and serotonin is more complicated.

However, when dopamine and norepinephrine systems become highly activated, the balance between activation and emotional regulation can be disturbed.

For this patient, the symptoms suggested that simply increasing dopamine and norepinephrine was not providing the right overall balance.

PPI Recommended a Different ADHD Strategy

The PPI pharmacist recommended discussing a switch from a strong stimulant approach to a:

Non-stimulant medication — Atomoxetine

Atomoxetine works differently from amphetamine. It mainly blocks the Norepinephrine transporter. This increases norepinephrine signaling and can also indirectly increase dopamine in the prefrontal cortex. But unlike amphetamine, atomoxetine does not produce the same strong release of dopamine and norepinephrine.

A simplified comparison is:

Amphetamine

1. Strongly increases dopamine + norepinephrine release
2. Potentially too activating for this patient

versus:

Atomoxetine

1. Gradually enhances norepinephrine and prefrontal dopamine signaling
2. Potentially smoother support for attention and executive function

Supporting Emotional Regulation

Because anxiety, mood and emotional regulation were also important concerns, the PPI pharmacist additionally recommended discussing a: Low-dose SSRI

with the treating clinician.

The goal was not to treat ADHD with an SSRI.

Instead, the strategy was to address two different sets of symptoms:

• Atomoxetine for: Attention and executive function
• Low-dose SSRI for: Anxiety, mood and emotional regulation The final medication decisions and dosing remained with the patient’s treating healthcare professional.

What Happened Next?

The treatment strategy was changed.

A few months later, the patient’s mother contacted the PPI pharmacist by email.

The difference was remarkable. The patient had:

• Returned to school
• Improved significantly
• Better attention
• Better emotional control
• Was doing extremely well What had once appeared to be an increasingly unmanageable situation had improved dramatically after the medication strategy was changed.

Why This Case Matters

If the treatment decision had been based only on: “Does the stimulant improve attention?” the medication might have appeared successful.

It did improve attention.

But the patient as a whole was doing worse.

PPI instead considered:

• Attention
• Anxiety
• Sleep
• Impulsivity
• Emotional regulation
• Dopamine and norepinephrine pathway genetics
• How strongly the medication increases those neurotransmitters A different treatment approach emerged

The Bigger Lesson

ADHD treatment is not simply about: “Increasing dopamine.”

It is about finding the right amount of support for:

• Dopamine
• Norepinephrine without causing excessive activation.

For this patient:

Amphetamine improved attention

but:

1. The overall catecholamine effect appeared too strong
2. Anxiety, insomnia, agitation and impulsivity increased

A non-stimulant strategy provided a different way to support attention without the same strong neurotransmitter release.

The Takeaway

A medication can improve one symptom and still be the wrong overall treatment for a particular patient.

The important question is not simply: “Can the patient concentrate better?” but: “Is the patient functioning better overall?”

PPI considers:

• Symptoms
• Medication response
• Pharmacokinetics
• Dopamine and norepinephrine pathway genetics
• Medication mechanism A more individualized approach to ADHD treatment

Important Note

This is an individual patient experience. COMT, MAOA or MAOB results cannot by themselves determine a person’s dopamine or norepinephrine levels or prove that amphetamine will cause overstimulation. PPI’s genetic assessments describe possible inherited tendencies in neurotransmitter regulation, not direct measurements of brain chemicals.

Atomoxetine is not automatically preferable to stimulants for people with lower COMT activity, and SSRIs are not treatments for the core symptoms of ADHD. Treatment decisions must also consider the patient’s diagnosis, symptoms, medication history, side effects, other medications and clinical circumstances. The genetic findings are used as supportive information alongside the complete clinical picture, not as stand-alone prescribing rules.