Table 1.
Commonly-prescribed serotonin-norepinephrine reuptake inhibitors.
| Drug (FDA Approval) |
FDA Approved Indications for Use | Bioavailability (Oral) | Protein Binding | Metabolism | Elimination | T1/2 (Hours) | Severe Side Effects |
|---|---|---|---|---|---|---|---|
| Desvenlafaxine (2008) | Major Depressive Disorder | 80% | 30% | Hepatic; conjugation, primary; CYP3A4, minor pathway | Renal: 45%, unchanged; up to 24% changed | 10–11.1 | Hypertension, angioedema, suicidal ideation, serotonin syndrome |
| Duloxetine (2004) | Major Depressive Disorder, Generalized Anxiety Disorder, Fibromyalgia, Diabetic Peripheral Neuropathy, Musculoskeletal pain | 30–80% | >90% | Hepatic: P450 CYP2D6 and CYP1A2 via conjugation and oxidation | Fecal: 20% Renal: 70% as metabolites | 12 | Hypertensive crisis, Steven-Johnson Syndrome, withdrawal syndrome, serotonin syndrome, liver failure |
| Levomilnacipran (2013) | Major Depressive Disorder | 92% | 22% | Desethylation by CYP3A4, and hydroxylation with further conjugation | Renal: 58% unchanged, 27% identifiable metabolites | 12 | Hypertension, suicidal ideation, serotonin syndrome, drug withdrawal, seizure |
| Milnacipran (1996) | Fibromyalgia | 85–90% | 13% | Hepatic | Renal: 50% to 60% unchanged drug | 6–8 | Hypertensive crisis, Erythema multiforme, Stevens-Johnson syndrome, Fulminant hepatitis, suicidal ideation, serotonin syndrome |
| Tramadol (1977) | Pain management | 70–75% | 20% | Hepatic: extensive via CYP2D6 and CYP3A4, conjugation, N- and O-demethylation, and glucuronidation or sulfation | Renal excretion: 60% as metabolite; approximately 30% unchanged | 5.6–6.7 | Dyspnea, respiratory depression, serotonin syndrome |
| Venlafaxine (1994) | Panic disorder, generalized anxiety disorder, major depressive disorder, social phobia | 42% | 27–30% | Hepatic: extensive first-pass via P450 CYP2D6 | Fecal: 2% Renal: 87%, 82% as metabolites, 5% unchanged |
5 | Neuroleptic malignant syndrome, Serotonin syndrome, suicidal ideation |