Can You Take Addyi, Trazodone, and Gabapentin Together?
No, you should not take Addyi (flibanserin), trazodone, and gabapentin together due to dangerous additive central nervous system (CNS) depression effects and significantly increased risks of hypotension, syncope, excessive sedation, and accidental injury.
Critical Safety Concerns with This Combination
CNS Depression Risk from Multiple Agents
The 2019 American Geriatrics Society Beers Criteria explicitly warns against concurrent use of three or more CNS agents (including antidepressants like trazodone, antiepileptics like gabapentin, and other CNS depressants) due to increased fall risk and excessive sedation 1
Addyi's FDA label specifically states that CNS depression risk is increased when taken with other CNS depressants, and patients should not drive or engage in activities requiring alertness until at least 6 hours after taking Addyi 2
Both trazodone and gabapentin have sedative properties that are additive when combined, requiring dosage adjustments to avoid excessive sedation 3
Hypotension and Syncope Risk
Addyi alone can cause hypotension (0.2% incidence) and syncope (0.4% incidence) even without other medications 2
The risk of hypotension and syncope increases substantially when Addyi is combined with other CNS depressants 2
Trazodone has known hypotensive effects through alpha2-adrenergic receptor antagonism 3
Specific Contraindications and Warnings
Addyi must be taken at bedtime specifically because administration during waking hours increases risks of hypotension, syncope, accidental injury, and CNS depression 2
The combination of trazodone and gabapentin alone shows synergistic effects, meaning their combined impact is greater than additive 4
Adding a third CNS depressant (Addyi) to an already synergistic combination (trazodone-gabapentin) creates an unacceptable safety profile 1, 2
Clinical Evidence Against This Combination
Research on Trazodone-Gabapentin Combination
Studies demonstrate that trazodone and gabapentin produce synergistic antinociceptive effects even at low doses (trazodone 0.3 mg/kg, gabapentin 3 mg/kg), indicating their combined CNS effects are amplified 4
A fixed-dose combination study of trazodone and gabapentin showed treatment-emergent adverse events primarily involving nervous system and gastrointestinal disorders, with the combination requiring careful monitoring 5
Addyi Safety Profile
Addyi clinical trials showed 21% incidence of somnolence, sedation, or fatigue compared to 8% with placebo 2
The FDA label emphasizes that CNS depression risk increases when Addyi is combined with other CNS depressants 2
Alternative Approaches
If Treating Multiple Conditions
For hypoactive sexual desire disorder (HSDD): Use Addyi as monotherapy at bedtime, discontinuing or avoiding other CNS depressants 2
For neuropathic pain: Use the trazodone-gabapentin combination without Addyi, as this pairing has demonstrated efficacy and acceptable safety when properly dosed 5, 6, 4
For insomnia/anxiety with pain: Consider trazodone-gabapentin combination for pain with sleep benefits, but avoid adding Addyi 3, 6
Timing Considerations
If transitioning between regimens, allow appropriate washout periods between medications 2
Addyi requires 2 days washout before starting other medications that could interact 2
Common Pitfalls to Avoid
Never assume that low doses of multiple CNS depressants are safe - the Beers Criteria specifically warns against three or more CNS agents regardless of dose 1
Do not take Addyi during waking hours even if other medications seem well-tolerated at bedtime 2
Avoid alcohol entirely when taking any of these medications, as alcohol further increases hypotension and syncope risk with Addyi 2
Do not drive or operate machinery for at least 6 hours after taking this combination, though the combination itself should be avoided 2