Tricyclic antidepressants were among the first antidepressants developed. They have largely been superseded by newer antidepressants that have less side effects, although they may still suit certain people or be effective when other antidepressants have been ineffective. tricyclic antidepressants; palliative care; We read with interest the review article on alternative opioids to morphine in palliative care. 1 The author has mentioned in detail various factors—biomedical, genetic, and psychological—which influence the effect of opioids. Articles from Postgraduate Medical Journal are provided here courtesy of BMJ Group Serotonin Syndrome: Is It a Reason to Avoid the Use of Tramadol With Antidepressants?. SNRIs, tricyclic antidepressants (TCAs), and triptans (eg, sumatriptan), antipsychotics, anticonvulsants. Concomitant use of tramadol increases the seizure risk in patients taking: •Selective serotonin re-uptake inhibitors (SSRI antidepressants or anorectics), •Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), or •Other opioids. Tricyclic antidepressants* (eg amitriptyline, clomipramine, desipramine, imipramine, maprotline and trimipramine) Warfarin* Potential serotonin syndrome when combined with: Other serotonin-enhancing antidepressants Tramadol Fentanyl Buspirone St John’s Wort Lithium Ondansetron Linezolid Increased risk of bleeding (particularly upper GI bleed) with: NSAIDs Warfarin and other anticoagulants. Drug Interactions. Tramadol accounts for a significant number of drug interactions. For example, in an Australian veterans study, Roughead et al 8 examined adverse drug interactions in 46,859 participants taking antidepressants. Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains three rings of atoms. Both tramadol and SSRIs lower seizure threshold. Serotonin syndrome reported with concurrent use Use the combination of tramadol and an SSRI very cautiously especially at high doses. Alternative analge-sic may be preferable All Tricyclic antidepres-sants Increased plasma concentrations of TCA and increased adverse effects. Risk of serotonin syndrome especially with clomipramine Increases are. Tricyclic antidepressants. As such, as tramadol is related to venlafaxine, the same conditions apply. This is likely due to venlafaxine's relatively short half-life and therefore rapid clearance upon discontinuation. Overdose.