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Trazodone

Desyrel, Oleptro

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Atypical antidepressant used off-label to improve deep sleep architecture.

Trazodone is a serotonin antagonist and reuptake inhibitor (SARI) primarily used as an antidepressant. For healthspan, it is widely used off-label at low doses as a non-addictive hypnotic to improve sleep architecture, particularly increasing slow-wave (deep) sleep. High-quality sleep is foundational for cellular repair, glymphatic clearance in the brain, and hormonal regulation, making it a key leverage point for longevity.

Verdict

Effective sleep aid, but requires prescription and awareness of side effects.

HEALTHSPAN IMPACT

Moderate

RISK LEVEL

Moderate

EVIDENCE GRADE

A

MONTHLY COST

$5 - $20

Protocol

  • 25-100 mg taken 30-60 minutes before bedtime for sleep quality improvement.

Flags

  • Risk of serotonin syndrome when combined with other serotonergic agents (e.g., SSRIs, MAOIs).
  • May cause significant next-day grogginess or 'hangover' effect.
  • Rare but serious risk of priapism (prolonged erection) requiring immediate medical attention.
  • Potential for orthostatic hypotension (dizziness upon standing), increasing fall risk.
  • Use with caution in individuals with pre-existing cardiac conditions due to arrhythmia risk.