title: SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants.
abstract: The class of serotonin and norepinephrine reuptake inhibitors (SNRIs) now comprises three medications: venlafaxine, milnacipran, and duloxetine. These drugs block the reuptake of both serotonin (5-HT) and norepinephrine with differing selectivity. Whereas milnacipran blocks 5-HT and norepinephrine reuptake with equal affinity, duloxetine has a 10-fold selectivity for 5-HT and venlafaxine a 30-fold selectivity for 5-HT. All three SNRIs are efficacious in treating a variety of anxiety disorders. There is no evidence for major differences between SNRIs and SSRIs in their efficacy in treating anxiety disorders. In contrast to SSRIs, which are generally ineffective in treating chronic pain, all three SNRIs seem to be helpful in relieving chronic pain associated with and independent of depression. Tolerability of an SNRI at therapeutic doses varies within the class. Although no direct comparative data are available, venlafaxine seems to be the least well-tolerated, combining serotonergic adverse effects (nausea, sexual dysfunction, withdrawal problems) with a dose-dependent cardiovascular phenomenon, principally hypertension. Duloxetine and milnacipran appear better tolerated and essentially devoid of cardiovascular toxicity.
authors.affiliation: Department of Psychiatry, University of California, San Diego, San Diego, CA, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Stahl
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Grady
authors.forename: Chantal
authors.initials: C
authors.lastname: Moret
authors.forename: Mike
authors.initials: M
authors.lastname: Briley
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D000068736:Duloxetine Hydrochloride; D006801:Humans; D066298:In Vitro Techniques; D000078764:Milnacipran; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D013876:Thiophenes / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D000069470:Venlafaxine Hydrochloride; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D003521:Cyclopropanes; D000068736:Duloxetine Hydrochloride; D000078764:Milnacipran; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes; D000069470:Venlafaxine Hydrochloride; D050493:Vesicular Monoamine Transport Proteins