What are the different stimulants, including their generic and trade names (e.g. Ritalin (methylphenidate), Adderall (amphetamines), Provigil (modafinil)), and how do they differ in terms of indications, mechanisms, and side effects?

Stimulant Medications: Generic Names, Trade Names, and Key Differences

Stimulant medications differ primarily in their mechanism of action, duration of effect, and side effect profiles, with methylphenidate and amphetamine-based medications being first-line for ADHD, while modafinil serves as a wakefulness-promoting agent for conditions like narcolepsy and fatigue.

Traditional Psychostimulants

Methylphenidate-Based Medications

• Generic Name: Methylphenidate
• Trade Names:
  • Ritalin (immediate-release)
  • Concerta XL (extended-release, 12-hour coverage)
  • Equasym XL/Metadate CD (extended-release, 8-hour coverage)
• Mechanism: Acts as substrate for monoamine transporters, primarily inhibiting dopamine reuptake and increasing extracellular dopamine and norepinephrine levels 1, 2
• Starting Dose: 2.5-5 mg daily or twice daily
• Dose Range: 5-30 mg/day, usually divided twice daily 3

Amphetamine-Based Medications

• Generic Name: Dextroamphetamine, Mixed Amphetamine Salts
• Trade Names:
  • Adderall (mixed amphetamine salts)
  • Dexedrine (dextroamphetamine)
• Mechanism: Causes release of dopamine and norepinephrine from presynaptic terminals and inhibits reuptake 3, 4
• Starting Dose: 2.5-5 mg daily or twice daily
• Dose Range: 5-30 mg/day, usually divided twice daily 3

Dexmethylphenidate

• Generic Name: Dexmethylphenidate
• Trade Names: Focalin
• Mechanism: Similar to methylphenidate but contains only the d-isomer
• Starting Dose: 2.5-5 mg daily or twice daily
• Dose Range: 5-20 mg/day, usually divided twice daily 3

Wakefulness-Promoting Agents

Modafinil

• Generic Name: Modafinil
• Trade Names: Provigil
• Mechanism: Complex mechanism involving dopamine transporter inhibition, but pharmacologic profile differs from traditional stimulants 5, 4
• Starting Dose: 50-100 mg daily
• Dose Range: 50-400 mg/day, may be divided twice daily 3
• Unique Properties: Promotes wakefulness with less potential for cardiovascular effects and abuse compared to traditional stimulants 5

Armodafinil

• Generic Name: Armodafinil
• Trade Names: Nuvigil
• Mechanism: R-enantiomer of modafinil with longer half-life
• Starting Dose: 50-150 mg daily
• Dose Range: 150-250 mg/day 3

Key Differences Between Stimulant Classes

Indications

1. Traditional Stimulants (Methylphenidate/Amphetamines):

   • Primary indication: ADHD 1
   • Secondary uses: Treatment-resistant depression, narcolepsy 6

2. Modafinil/Armodafinil:

   • Primary indications: Narcolepsy, shift work sleep disorder, obstructive sleep apnea 5
   • Off-label uses: Cancer-related fatigue, multiple sclerosis fatigue 3, 6

Mechanism Differences

1. Traditional Stimulants:

   • Direct sympathomimetic effects
   • Primarily increase dopamine and norepinephrine throughout the brain 2
   • Low doses improve prefrontal cortex function while high doses impair it 2

2. Modafinil:

   • Selectively increases neuronal activation in discrete brain regions 5
   • Binds to dopamine transporter but with different pharmacologic profile 5
   • Wake-promoting effects not antagonized by dopamine receptor antagonists 5

Side Effect Profiles

1. Traditional Stimulants:

   • More pronounced cardiovascular effects (hypertension, tachycardia)
   • Higher risk of insomnia, appetite suppression, growth effects in children
   • Greater potential for abuse and dependence 4

2. Modafinil:

   • Generally milder cardiovascular effects
   • Lower abuse potential (though still Schedule IV controlled substance)
   • Common side effects include headache, anxiety, insomnia 5, 4

Duration of Action

1. Immediate-Release Formulations:

   • Methylphenidate (Ritalin): 3-4 hours, requires multiple daily dosing 1

2. Extended-Release Formulations:

   • Concerta XL: 12-hour coverage using OROS technology 1
   • Equasym XL/Metadate CD: 8-hour coverage 1
   • Improves adherence compared to immediate-release preparations 1

Important Clinical Considerations

Contraindications

• Avoid all stimulants in patients with:
  • Uncontrolled hypertension
  • Underlying coronary artery disease
  • Tachyarrhythmias 3, 1

Overdose Management

• Traditional stimulants: Focus on interrupting sympathomimetic syndrome with benzodiazepines 4
• Modafinil overdose: Generally moderate severity, supportive care with focus on sedation 4

Monitoring Requirements

• Regular monitoring of blood pressure, heart rate
• Height and weight monitoring in children (growth suppression possible)
• Assessment for side effects including sleep disturbances and appetite changes 1

Conversion Between Medications

When switching from immediate-release to extended-release methylphenidate, use this conversion guide:

• 10-15 mg/day IR → 18 mg Concerta once daily
• 20 mg/day IR → 18 mg Concerta once daily
• 30-45 mg/day IR → 36 mg Concerta once daily
• 40-60 mg/day IR → 54 mg Concerta once daily 1

The selection of stimulant medication should be based on the specific condition being treated, desired duration of action, and individual tolerability of side effects, with careful consideration of contraindications in patients with cardiovascular risk factors.