SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants

CNS Spectr. 2005 Sep;10(9):732-47. doi: 10.1017/s1092852900019726.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use*
  • Cyclohexanols / adverse effects
  • Cyclohexanols / pharmacology*
  • Cyclohexanols / therapeutic use*
  • Cyclopropanes / adverse effects
  • Cyclopropanes / pharmacology
  • Cyclopropanes / therapeutic use
  • Depressive Disorder, Major / drug therapy*
  • Duloxetine Hydrochloride
  • Humans
  • In Vitro Techniques
  • Milnacipran
  • Norepinephrine / antagonists & inhibitors*
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / pharmacology*
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Thiophenes / adverse effects
  • Thiophenes / pharmacology*
  • Thiophenes / therapeutic use*
  • Venlafaxine Hydrochloride
  • Vesicular Monoamine Transport Proteins / antagonists & inhibitors

Substances

  • Antidepressive Agents
  • Cyclohexanols
  • Cyclopropanes
  • Serotonin Uptake Inhibitors
  • Thiophenes
  • Vesicular Monoamine Transport Proteins
  • Venlafaxine Hydrochloride
  • Duloxetine Hydrochloride
  • Milnacipran
  • Norepinephrine