| Pregabalin (Lyrica) and gabapentin (Neurontin) | May increase toxic effects of CNS depressants,* SSRIs, thiazolidinediones |
| Toxic effects may be increased by CNS depressants,* AcCHS inhibitors, hydroxyzine, and magnesium sulfate |
| Amitriptyline | May increase toxic effects of CNS depressants,* QTc-prolonging agents,† SSRIs, St. John's wort, sulfonylureas, tramadol, and warfarin (Coumadin) |
| Effectiveness can be decreased by St. John's wort, AcCHS inhibitors, and carbamazepine (Tegretol) |
| Toxic effects can be increased by CNS depressants,* QTc-prolonging agents,† SSRIs, St. John's wort, antiemetics (e.g., 5-HT3 antagonists, ondansetron [Zofran]), antipsychotic agents, and bupropion (Wellbutrin) |
| Absolutely contraindicated with MAO inhibitors |
| Duloxetine (Cymbalta) | May increase toxic effects of CNS depressants,* antiplatelet agents, alpha and beta agonists, anticoagulants (e.g., warfarin), antipsychotic agents |
| Absolutely contraindicated with MAO inhibitors |
| May decrease effects of TCAs and linezolid (Zyvox) |
| Toxic effects may be increased by CNS depressants,* alcohol, antiemetics (e.g., 5-HT3 antagonists, ondansetron), antipsychotic agents, metoclopramide (Reglan) |
| Effectiveness may be decreased by CYP1A2 inducers‡ |
| Venlafaxine | May increase toxic effects of CNS depressants* and SSRIs |
| May decrease effectiveness of alpha-2 agonists |
| Absolutely contraindicated with MAO inhibitors and linezolid |
| Toxic effects may be increased by CNS depressants,* CYP2D6 inhibitors,§ CYP3A4 inhibitors,|| and SSRIs |
| Tramadol | May increase toxic effects of CNS depressants* and SSRIs |
| Toxic effects may be increased by CNS depressants,* SSRIs, and TCAs |
| Tapentadol ER (Nucynta ER) | Absolutely contraindicated with MAO inhibitors and mixed agonist and antagonist opioids |
| May increase toxic effects of CNS depressants,* diuretics, and desmopressin |
| Toxic effects may be increased by alcohol, amphetamines, anticholinergic agents, and magnesium sulfate |
| Opioids (oxycodone controlled release) | May increase toxic effects of CNS depressants,* MAO inhibitors, and SSRIs |
| Effectiveness of medication can be increased by CYP3A4 inducers¶ |
| Toxic effects may be increased by CNS depressants* |
