Dexamfetamine

Clinical studies show that both dexamfetamine and its longer-acting prodrug, lisdexamfetamine, are broadly comparable in effectiveness to methylphenidate for treating ADHD. However, individuals respond differently—around 10% of patients show limited benefit from either stimulant class (16). Some research suggests slightly greater overall efficacy for amphetamine-based stimulants compared with methylphenidate (17).

Abuse Potential

The potential for abuse among ADHD patients prescribed dexamfetamine is very low (17).
This is because:

• Individuals with ADHD typically begin with lower dopamine activity in the brain’s reward centres.

• Therapeutic dosing uses oral tablets, not rapid-delivery routes such as smoking or injection.

• Blood levels rise slowly, avoiding the sharp peaks linked to addiction. In fact, many ADHD patients find taking their medication consistently each day more challenging than stopping misuse (17).

Cardiovascular Risk

Both dexamfetamine and lisdexamfetamine can raise blood pressure and heart rate by stimulating the adrenergic “fight-or-flight” system (2). Typical effects include mild tachycardia, arrhythmia, or hypertension, which usually resolve when treatment is stabilised. Blood pressure and heart function should be monitored throughout therapy (4). Use is contraindicated in individuals with heart abnormalities (18).

Psychiatric Considerations

Dexamfetamine influences the amygdala, a brain region that processes anxiety and emotional reactivity (6). Although it helps many people feel calmer and more focused, it can occasionally trigger anxiety, irritability, or mood swings. Pharmacovigilance data also report rare cases of psychosis, aggression, or hostility, particularly in vulnerable individuals (6). For patients with a history of psychiatric illness or depression, dexamfetamine should be prescribed cautiously and monitored closely (18).

Dexamfetamine Side Effects

Dexamfetamine’s side effects are usually related to its stimulant effect on the brain and body.

Most Common Side Effects (18):

• Difficulty sleeping (insomnia)

• Loss of appetite or weight loss

• Headache

• Dry mouth

• Nausea or stomach discomfort

• Feeling nervous or restless

Less Common Side Effects:

• Elevated heart rate or blood pressure

• Dizziness or fainting

• Mood changes or irritability

• Rarely, hallucinations or aggression

If side effects are troublesome or persistent, your prescriber may adjust your dose or suggest an alternative medication.

Currently, CYP2D6 is the main gene known to affect how dexamfetamine is processed. Patients who are poor metabolisers may require a lower dose or closer monitoring (21). Pharmacogenomic testing can provide early insight, helping your clinician tailor the starting dose and anticipate side-effect risk. Because dexamfetamine affects both cardiovascular and emotional regulation, understanding your genetic profile allows safer, more personalised prescribing.

Related Medications:

Other ADHD treatments with similar goals include:

• Lisdexamfetamine (Elvanse) – a longer-acting prodrug that releases dexamfetamine gradually

• Methylphenidate (Ritalin, Concerta) – a shorter-acting stimulant

• Atomoxetine (Strattera) – a non-stimulant option targeting noradrenaline

• Viloxazine (Qelbree) – a newer non-stimulant medicine