How Long Until It Works

• Some immediate effects can be seen with first dosing

• Can take several weeks to attain maximum therapeutic benefit

If It Works (for adhd)

• The goal of treatment of ADHD is reduction of symptoms of inattentiveness, motor hyperactivity, and/or impulsiveness that disrupt social, school, and/or occupational functioning

• Continue treatment until all symptoms are under control or improvement is stable and then continue treatment indefinitely as long as improvement persists

• Reevaluate the need for treatment periodically

• Treatment for ADHD begun in childhood may need to be continued into adolescence and adulthood if continued benefit is documented

If It Doesn’t Work (for adhd)

• Consider adjusting dose or switching to another formulation of d,l-methylphenidate or to another agent

• Consider behavioral therapy

• Consider the presence of noncompliance and counsel patient and parents

• Consider evaluation for another diagnosis or for a comorbid condition (e.g., bipolar disorder, substance abuse, medical illness, etc.)

✽ Some ADHD patients and some depressed patients may experience lack of consistent efficacy due to activation of latent or underlying bipolar disorder, and require either augmenting with a mood stabilizer or switching to a mood stabilizer

Best Augmenting Combos for Partial Response or Treatment Resistance

✽ Best to attempt other monotherapies prior to augmenting

• For the expert, can combine immediate-release formulation with a sustained-release formulation of d,l-methylphenidate for ADHD

• For the expert, can combine with modafinil or atomoxetine for ADHD

• For the expert, can occasionally combine with atypical antipsychotics in highly treatment-resistant cases of bipolar disorder or ADHD

• For the expert, can combine with antidepressants to boost antidepressant efficacy in highly treatment-resistant cases of depression while carefully monitoring patient

Tests

• Before treatment, assess for presence of cardiac disease (history, family history, physical exam)

• Blood pressure should be monitored regularly

• In children, monitor weight and height

• Periodic complete blood cell and platelet counts may be considered during prolonged therapy (rare leukopenia and/or anemia)

METHYLPHENIDATE (D,L): SIDE EFFECTS

How Drug Causes Side Effects

• Increases in norepinephrine peripherally can cause autonomic side effects, including tremor, tachycardia, hypertension, and cardiac arrhythmias

• Increases in norepinephrine and dopamine centrally can cause CNS side effects such as insomnia, agitation, psychosis, and substance abuse

Notable Side Effects

✽ Insomnia, headache, exacerbation of tics, nervousness, irritability, overstimulation, tremor, dizziness

• Anorexia, nausea, abdominal pain, weight loss

• Can temporarily slow normal growth in children (controversial)

• Blurred vision

• Transdermal: application site reactions, including contact sensitization (erythema, edema, papules, vesicles)

Life-Threatening or Dangerous Side Effects

✽ Rare priapism

• Psychotic episodes, especially with parenteral abuse

• Seizures

• Palpitations, tachycardia, hypertension

• Rare neuroleptic malignant syndrome

• Rare activation of hypomania, mania, or suicidal ideation (controversial)

• Cardiovascular adverse effects, sudden death in patients with preexisting cardiac structural abnormalities

Weight Gain

• Reported but not expected

• Some patients may experience weight loss

Sedation

• Reported but not expected

• Activation much more common than sedation

What to Do About Side Effects

• Wait

• Adjust dose

• Switch to another formulation of d,l-methylphenidate

• Switch to another agent

• For insomnia, avoid dosing in afternoon/evening

Best Augmenting Agents for Side Effects

• Beta blockers for peripheral autonomic side effects

• Dose reduction or switching to another agent may be more effective since most side effects cannot be improved with an augmenting agent

METHYLPHENIDATE (D,L): DOSING AND USE

Usual Dosage Range

• ADHD (oral): up to 2 mg/kg per day in children 6 years and older, with a maximum daily dose of 60 mg/day; in adults usually 20–30 mg/day, but may use up to 40–60 mg/day

• ADHD (transdermal): 10–30 mg/9 hours

• Narcolepsy: 20–60 mg/day in 2–3 divided doses

Dosage Forms

• Immediate-release tablets 5 mg, 10 mg, 20 mg (Ritalin, Methylin, generic methylphenidate)

• Immediate-release chewable tablets 2.5 mg, 5 mg, 10 mg

• Oral solution 5 mg/mL, 10 mg/5 mL

• Older sustained-release tablets 10 mg, 20 mg (Metadate ER, Methylin ER); 20 mg (Ritalin SR)

✽ Newer sustained-release capsules 20 mg, 30 mg, 40 mg (Ritalin LA); 10 mg, 20 mg, 30 mg (Metadate CD)

✽ Newer sustained-release tablets 18 mg, 27 mg, 36 mg, 54 mg (Concerta)

• Transdermal patch 27 mg/12.5 cm², (10 mg/9 hours), 41.3 mg/18.75 cm² (15 mg/9 hours), 55 mg/25 cm² (20 mg/9 hours), 82.5 mg/37.5 cm² (30 mg/9 hours)