Cyclobenzaprine and Trazodone interaction
Cyclobenzaprine and Trazodone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Cyclobenzaprine (TONMYA) label · effective 2026-08-14
Hyperpyretic crisis seizures and deaths have occurred in patients who received cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitors drugs.
Based on its structural similarity to TCAs, concomitant use of TONMYA with: MAO inhibitors may be life-threatening [see Contraindications (4) ] , Alcohol, barbiturates, and other CNS depressants may increase the risk of adverse reactions associated with these drugs, Tramadol may increase the seizure risk, Guanethidine or other similar acting drugs may block the…
If serotonin syndrome symptoms occur with the use of other serotonergic drugs, immediately discontinue TONMYA.
Other serotonergic Drugs: Serotonin syndrome has been reported ( 5.2 , 7 )
If concomitant treatment with TONMYA and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dosage increases.
From the Trazodone (RALDESY TM) label · effective 2026-09-01
Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone.
If concomitant use of RALDESY with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St.
CNS Depressants: RALDESY may enhance effects of alcohol, barbiturates, or other CNS depressants ( 7 ).
Other Serotonergic Drugs Clinical Impact: The concomitant use of serotonergic drugs, including RALDESY and other serotonergic drugs increases the risk of serotonin syndrome.
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Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.