Lisdexamfetamine

Lisdexamfetamine and dexamfetamine share a common goal: to increase the brain’s levels of dopamine and noradrenaline, improving focus and behavioural control (2, 6, 11). However, lisdexamfetamine achieves this through a more gradual process, leading to a gentler onset and offset of action.

Because of its design, lisdexamfetamine often provides smoother symptom control and fewer “crash” effects later in the day (17). It also has a lower potential for abuse than older stimulants (17, 18).

Abuse Potential

Although amphetamines have a history of misuse, the abuse potential of lisdexamfetamine in ADHD treatment is very low (17). This is because:

• The medicine is a prodrug—it must first be converted in the body to dexamfetamine before it becomes active.

• This conversion occurs gradually inside red blood cells, preventing rapid increases in dopamine.

• It cannot be misused effectively via smoking, injection, or snorting, as it needs metabolic activation (17).

Some studies show conflicting data on abuse potential, but overall, lisdexamfetamine’s slow activation makes it safer and less reinforcing than short-acting amphetamines (17).

Cardiovascular Risk

Like other stimulants, lisdexamfetamine increases noradrenaline activity, which can lead to mild increases in heart rate and blood pressure (2). Although these effects are usually small, blood pressure and cardiovascular status should be monitored throughout treatment (4). It is contraindicated in people with structural heart abnormalities (18).

Psychiatric Considerations

Lisdexamfetamine influences areas of the brain involved in emotion and anxiety, particularly the amygdala (6). While most patients experience improved focus and emotional regulation, some may develop mild anxiety, irritability, or agitation. As with dexamfetamine, rare cases of psychotic symptoms or aggression have been reported (6). For those with a history of depression or psychiatric illness, careful supervision is recommended (18).

Lisdexamfetamine Side Effects

Most side effects are mild and lessen over time as the body adjusts.

The most common reactions include (18):

• Loss of appetite

• Insomnia

• Headache

• Dry mouth

• Nausea or abdominal discomfort

• Nervousness or mood changes

Less commonly, patients may experience elevated blood pressure, faster heartbeat, or irritability. Any persistent or severe side effects should be discussed with your prescribing clinician.

Genetic variation in the CYP2D6 enzyme can affect how efficiently lisdexamfetamine is converted and metabolised. Pharmacogenomic (PGx) testing can identify whether you are a slow or fast metaboliser, helping your clinician tailor the starting dose and monitoring plan (21).

If your test shows reduced CYP2D6 activity, your doctor may start with a lower dose or observe more closely for side effects. Those with ultra-rapid metabolism may need dose adjustments or alternative medications.

Overall, lisdexamfetamine remains a well-established and well-tolerated ADHD treatment, with most patients experiencing significant improvement when carefully monitored (12, 18, 21).

Related Medications:

Other medicines used for ADHD include:

• Dexamfetamine – the active form released by lisdexamfetamine; shorter-acting.

• Methylphenidate – a stimulant with different mechanisms of action.

• Atomoxetine – a non-stimulant that targets noradrenaline reuptake.

• Viloxazine – a newer non-stimulant option for ADHD symptom control.