Amphetamines Are Not Suitable First-Line Treatment for Acute Depression
Amphetamines should not be used as first-line treatment for acute depression. Current clinical guidelines strongly recommend psychosocial interventions and standard antidepressants as first-line treatments for depression, with amphetamines reserved only for specific circumstances 1, 2.
Evidence Against Amphetamines as First-Line Treatment
Guidelines and Recommendations
- The American Academy of Child and Adolescent Psychiatry explicitly states that amphetamines should only be prescribed when treating suicidal children and adolescents with ADHD, not as primary treatment for depression 1
- Clinical guidelines recommend psychosocial interventions as first-line treatment for stimulant addiction, highlighting concerns about amphetamine use 1
- Current practice guidelines from the American Psychiatric Association and American Academy of Family Physicians do not include amphetamines among recommended first-line treatments for depression 2
Safety Concerns
- Amphetamines have a high abuse potential and can be neurotoxic 3
- They may disinhibit some individuals who then exhibit aggression and suicide attempts 1
- Prolonged stimulant treatment effects have not been fully explored, and understanding such effects remains a research priority 3
- Prescription amphetamines are among the most commonly abused medications 3
- Occasional case reports indicate prescription use can produce marked psychological adverse events, including stimulant-induced psychosis 3
First-Line Treatments for Depression
Recommended Pharmacological Options
- SSRIs are the preferred pharmacological treatment for depression, with sertraline demonstrating efficacy in treating both depression and anxiety symptoms 2
- Other first-line options include:
- Bupropion (activating effect, improves energy)
- Mirtazapine (promotes sleep, appetite, and weight gain)
- SNRIs like venlafaxine for certain patients 2
Evidence for Psychostimulants in Limited Contexts
While not first-line, there is limited evidence supporting psychostimulants in specific situations:
- A Cochrane review found that psychostimulants may reduce symptoms of depression in the short term, but noted that "larger high quality trials with longer follow-up and evaluation of tolerance and dependence are needed" 4
- Some evidence suggests efficacy for secondary depression in medical illness, with 82% of patients showing improvement in one retrospective chart review 5
- The rapid amelioration of depressive symptoms with traditional psychostimulants is often dramatic but short-lived 6
When Stimulants Might Be Considered (Not First-Line)
- For treatment-resistant depression after multiple failed trials of standard antidepressants
- For depression with prominent fatigue symptoms (modafinil specifically) 6
- For secondary depression in medical illness 5
- For patients with comorbid ADHD and depression 1
Conclusion
The evidence clearly indicates that amphetamines should not be used as first-line treatment for acute depression. Their high abuse potential, risk of neurotoxicity, and limited evidence for efficacy in depression make them unsuitable as initial therapy. SSRIs and other standard antidepressants, along with psychosocial interventions, remain the evidence-based first-line approaches for treating acute depression.