SNRI (Serotonin-Norepinephrine Reuptake Inhibitor)
Inhibits reuptake of serotonin and norepinephrine, enhancing neurotransmission in the prefrontal cortex and spinal pathways. As the active metabolite of venlafaxine, it provides consistent serotonergic and noradrenergic activity without CYP2D6 variability.
Major depressive disorder (MDD)
Generalized anxiety disorder (GAD), fibromyalgia, vasomotor symptoms associated with menopause
Oral extended-release tablets (25 mg, 50 mg, 100 mg)
50 mg p.o. daily; higher doses are generally not more effective and increase adverse effects
50–100 mg/day
Half-life ~11 hours; primarily excreted unchanged in urine; minimal hepatic metabolism; no CYP2D6 activation required
Nausea, dry mouth, constipation, dizziness, insomnia, somnolence, sweating, and dose-dependent hypertension
Hypertension, serotonin syndrome, withdrawal symptoms with abrupt discontinuation, SIADH
Monitor blood pressure periodically, especially at higher doses. Monitor for withdrawal with abrupt cessation.
Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD.
Desvenlafaxine may cause dose-related increases in blood pressure and should be used cautiously in patients with pre-existing hypertension. Its balanced serotonergic and noradrenergic activity may provide benefit for mood symptoms, cognitive dysfunction, or fatigue in patients with neurocognitive disorders such as multiple sclerosis (MS), post-stroke depression, or cognitive impairment associated with aging. Because desvenlafaxine bypasses CYP2D6 metabolism, it offers more predictable pharmacokinetics in patients with hepatic impairment or those taking multiple medications. Dose reductions are recommended in moderate to severe renal or hepatic impairment to reduce toxicity risk.