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-amphetamine 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-amphetamine 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

AMPHETAMINE (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, dry mouth, constipation, diarrhea, weight loss

• Can temporarily slow normal growth in children (controversial)

• Sexual dysfunction long-term (impotence, libido changes) but can also improve sexual dysfunction short-term

Life-Threatening or Dangerous Side Effects

• Psychotic episodes, especially with parenteral abuse

• Seizures

• Palpitations, tachycardia, hypertension

• 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 a long-acting stimulant

• 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

AMPHETAMINE (D,L): DOSING AND USE

Usual Dosage Range

• Narcolepsy: 5–60 mg/day in divided doses

• ADHD: 5–40 mg/day (divided doses for immediate release tablet, once daily morning dose for extended-release tablet)

Dosage Forms

• Immediate release tablet 5 mg double-scored, 7.5 mg double-scored, 10 mg double-scored, 12.5 mg double-scored, 15 mg double-scored, 20 mg double-scored, 30 mg double-scored

• Extended release tablet 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg

How to Dose

• Immediate release formulation in ADHD (ages 6 and older): initial 5 mg once or twice per day; can increase by 5 mg each week; maximum dose generally 40 mg/day; split daily dose with first dose on waking and every 4–6 hours thereafter

• Immediate-release formulation in narcolepsy (ages 12 and older): initial 10 mg/day; increase by 10 mg each week; give first dose on waking and every 4–6 hours thereafter

• Extended-release formulation in ADHD: initial 10 mg/day in the morning; can increase by 5–10 mg/day at weekly intervals; maximum dose generally 30 mg/day