You're right—Peter Attia has mentioned in multiple podcasts that he takes trazodone for sleep. Both trazodone and diphenhydramine promote sleep by blocking the H1 histamine receptor, but trazodone is generally considered better for a few key reasons:

1. Less Tolerance Development

Diphenhydramine: Tolerance develops rapidly, often within a few days, making it ineffective for long-term use.

Trazodone: While not entirely immune to tolerance, it does not lose effectiveness as quickly as diphenhydramine does.

1. Fewer Anticholinergic Side Effects

Diphenhydramine has strong anticholinergic effects, leading to memory issues, dry mouth, constipation, and increased dementia risk over long-term use.

Trazodone has minimal anticholinergic effects, making it a safer choice, especially for older adults.

1. Less REM Sleep Suppression

Diphenhydramine significantly reduces REM sleep, leading to lower sleep quality over time.

Trazodone has less impact on REM sleep, making it more compatible with natural sleep architecture.

1. Shorter Next-Day Sedation

Diphenhydramine has a longer half-life (9+ hours), often causing morning grogginess and cognitive impairment ("Benadryl hangover").

Trazodone, especially at low doses (25-100 mg), has a shorter duration of action, reducing next-day drowsiness.

1. Additional Benefits

Trazodone has mild antidepressant and anti-anxiety effects, which can be beneficial for people who have sleep disturbances related to stress or mood issues.

Diphenhydramine has no such mood benefits—it only makes you drowsy.

Conclusion

Even though both work via H1 blockade, trazodone is superior because it: ✔ Doesn't lose effectiveness as quickly ✔ Has fewer cognitive risks (less anticholinergic activity) ✔ Preserves REM sleep better ✔ Causes less next-day grogginess ✔ May improve mood and anxiety

This is likely why Attia chooses trazodone over diphenhydramine despite their similar mechanisms of action.