Methylphenidate

Methylphenidate is one of the most commonly prescribed medicines for attention deficit hyperactivity disorder (ADHD). It helps improve concentration, control impulsive behaviour, and manage restlessness by increasing the levels of certain brain chemicals—mainly dopamine and noradrenaline. While these effects can be highly beneficial, they can also influence the heart, mood, and sleep. It’s therefore important to understand how the medicine works, what side effects to look out for, and which health factors your doctor may need to monitor during treatment.

Cardiovascular Risk

By raising noradrenaline levels, methylphenidate can sometimes cause:

• Faster heartbeat (tachycardia)

• Irregular heartbeat (arrhythmias)

• Higher blood pressure (hypertension)

In healthy individuals without heart problems, these changes are usually mild (3). Still, guidelines recommend blood pressure and heart monitoring at the start of treatment, especially in the first 8 weeks (3, 4). Methylphenidate should not be prescribed to patients with known heart abnormalities or arrhythmias (3, 4, 1).

Psychiatric Adverse Events

Methylphenidate can sometimes trigger manic episodes or worsen existing psychiatric conditions. On the other hand, by treating ADHD effectively, it may help reduce related anxiety or depression (3).

Extra caution is needed for:

• Pre-school children

• Patients with tic disorders

• Adolescents vulnerable to substance misuse (3, 4)

Emotional Blunting and Creativity

Some people report emotional blunting, reduced spontaneity, or changes in creativity when taking methylphenidate. These effects vary greatly between individuals, and in some cases can lead to stopping the medication (3).

Methylphenidate Side Effects

Like all ADHD medicines, methylphenidate can cause side effects — though not everyone will experience them, and many improve once the body adjusts. Because the drug increases levels of dopamine and noradrenaline, most side effects relate to changes in appetite, mood, heart rate, or sleep. Some people notice mild effects such as reduced appetite or trouble sleeping, while others may experience mood swings or palpitations, especially during dose changes. Regular monitoring by your clinician helps to balance symptom control with comfort and safety.

The most common side effect in children is loss of appetite, reported in about 1 in 3 patients (3).

Other possible side effects include (3, 1):

• Insomnia

• Nervousness or agitation

• Nausea or vomiting

• Abdominal discomfort

• Weight loss

• Headaches

• Palpitations, fast heartbeat (tachycardia)

• Mood swings

Pharmacogenomic (PGx) testing can help explain why some people respond strongly to methylphenidate while others see limited benefit or experience side effects such as anxiety, appetite loss, or sleep disturbance. Unlike many antidepressants, methylphenidate’s metabolism is not heavily influenced by CYP enzymes. Instead, its effects depend more on how the brain’s dopamine and noradrenaline systems respond — areas influenced by genetic variants in receptors and enzymes such as ADRA2A and COMT.

People with certain ADRA2A variants (such as rs1800544 G/G) tend to show better treatment response and concentration control, while those with high-activity COMT variants may tolerate treatment more smoothly at the start. However, lower dopamine levels associated with COMT activity can also affect motivation and focus — meaning dosage or formulation adjustments may still be required.

These genetic insights don’t replace medical supervision but can support a more personalised approach to ADHD management — helping clinicians decide on the right dose, formulation, or even whether another medication might work better.

Related Medications:

There are several other medicines used to treat ADHD, each working through a slightly different mechanism. While methylphenidate increases dopamine and noradrenaline by blocking their reuptake, others act directly on the receptors or use different neurotransmitter systems.

Dexamphetamine

Dexamphetamine belongs to the amphetamine family. It works by stimulating the release of dopamine and noradrenaline rather than just blocking their reuptake. This often produces stronger effects, which can be helpful for some patients but may also increase the risk of side effects such as loss of appetite, jitteriness, or sleep problems.

Atomoxetine

Atomoxetine is a non-stimulant ADHD medication that works mainly on the noradrenaline system. It selectively inhibits the noradrenaline transporter (NET), improving focus and attention without the same degree of stimulation as methylphenidate or dexamphetamine. It’s often used when stimulants are not tolerated or not effective.

Viloxazine

Viloxazine is another non-stimulant option, originally developed as an antidepressant. It acts on both noradrenaline and serotonin systems, with additional effects on dopamine in key brain regions related to motivation and impulse control. It’s a newer alternative that may cause fewer sleep or appetite issues in some patients.

Together, these medications form a toolkit that allows clinicians to tailor treatment for each person’s unique neurochemical profile and daily needs.