Is amphetamine (amphetamine) a suitable first-line treatment for medical depression secondary to illness?

Amphetamine is NOT Recommended as First-Line Treatment for Depression Secondary to Medical Illness

Amphetamine should NOT be used as a first-line treatment for depression secondary to medical illness, as current clinical guidelines strongly recommend psychosocial interventions and standard antidepressants such as SSRIs as initial treatments. 1

First-Line Treatment Options for Depression Secondary to Medical Illness

Recommended First-Line Treatments:

• Psychosocial interventions:

  • Cognitive Behavioral Therapy (CBT)
  • Behavioral Activation (BA)
  • Structured physical activity and exercise
  • Mindfulness-Based Stress Reduction (MBSR)
  • Other psychosocial interventions with empirically supported components 2

• Pharmacological first-line options:

  • Selective Serotonin Reuptake Inhibitors (SSRIs)
    • Sertraline: 25-50 mg daily, maximum 200 mg daily
    • Citalopram: 10 mg daily, maximum 40 mg daily (20 mg maximum in elderly)
    • Escitalopram: 10 mg daily, maximum 20 mg daily
    • Fluoxetine: 10 mg daily, maximum 60 mg daily 1
  • Other antidepressants:
    • Bupropion: Start 37.5 mg every morning, maximum 150 mg twice daily
    • Mirtazapine: Start 7.5 mg at bedtime, maximum 30 mg at bedtime
    • Venlafaxine and other SNRIs 1

Role of Amphetamines in Depression Treatment

Amphetamines are not recommended as first-line treatment for depression secondary to medical illness for several important reasons:

1. Limited evidence: There is insufficient high-quality evidence from randomized controlled trials supporting their efficacy in treating depression 3

2. Short-lived benefits: While psychostimulants like amphetamine may produce rapid amelioration of depressive symptoms, these effects are often dramatic but short-lived 3

3. Safety concerns: Amphetamines have significant potential for abuse and dependence, and are contraindicated in patients with a history of recent stimulant drug abuse 2

4. Guideline recommendations: Major clinical guidelines do not recommend amphetamines as first-line treatment for depression 1

Limited Circumstances Where Amphetamines May Be Considered

Amphetamines may be considered in specific circumstances, but only after first-line treatments have failed:

• As adjunctive therapy for refractory depression 4
• In medically ill patients who cannot tolerate or have responded poorly to standard antidepressants 5
• For depression with prominent fatigue, particularly in terminally ill patients 2
• When rapid response is critically needed (though benefits may be short-lived) 6

Implementation Considerations

If considering amphetamines after failure of first-line treatments:

• Careful screening: Exclude contraindications such as:

  • Schizophrenia or psychotic disorders
  • Glaucoma
  • Existing liver disorders
  • Recent stimulant drug abuse 2

• Close monitoring: Watch for:

  • Signs of dependence or abuse
  • Cardiovascular effects
  • Psychiatric symptoms (anxiety, insomnia)
  • Drug interactions 2

• Time-limited use: Prescription should be facilitatory and time-limited unless for investigational purposes 3

Conclusion

For depression secondary to medical illness, the evidence strongly supports starting with psychosocial interventions (CBT, BA, structured physical activity) and/or standard antidepressants (SSRIs, SNRIs, bupropion, mirtazapine). Amphetamines should be reserved for specific circumstances where first-line treatments have failed or are contraindicated, and even then should be used with caution and for limited periods.