Methylphenidate (Ritalin, Concerta)

Class

Central nervous system stimulant

Mechanism

Blocks dopamine and norepinephrine reuptake transporters (DAT and NET), increasing synaptic concentrations of dopamine and norepinephrine, enhancing attention and alertness

FDA-Approved Use

Attention-deficit/hyperactivity disorder (ADHD), narcolepsy

Off-Label Use

Augmentation in treatment-resistant depression; agitation and aggression in neurodevelopmental disabilities (especially with ADHD), post-stroke apathy, fatigue in multiple sclerosis (MS), fatigue in traumatic brain injury (TBI), apathy in Parkinson’s disease (PD)

Formulation

Immediate-release (IR) tablets, extended-release (ER) tablets/capsules

Titration

IR: start 5–10 mg p.o. in the morning, titrate up as clinically indicated (usual range 10–60 mg/day); ER: start 18–20 mg once daily, titrate to 18–72 mg/day

Dose Range

IR 10–60 mg/day; ER 18–72 mg/day (individualized by clinical response)

Kinetics

Half-life approximately 3–4 hours (IR), longer for ER formulations; primarily metabolized hepatically; dosing typically once or twice daily depending on formulation

Common AEs

Decreased appetite, insomnia, anxiety, nausea, headache, elevated blood pressure and heart rate

Serious/Rare AEs

Potential for misuse, abuse, and dependence; cardiovascular events (rare)

Monitoring

Regular assessment of blood pressure, heart rate, sleep quality, mood symptoms, and risk of misuse or abuse

Black Box Warning

Risk of abuse and dependence; monitor carefully

Considerations

Methylphenidate may be used as augmentation in treatment-resistant depression and for addressing fatigue or apathy in cognitive disorders such as MS, TBI, or dementia, with close monitoring. Use cautiously in patients with a history of seizures, monitoring for potential lowering of seizure threshold or worsening sleep. Exercise caution in individuals with cardiovascular or psychiatric comorbidities, as stimulants may elevate blood pressure and exacerbate anxiety, insomnia, or affective instability.