Venlafaxine Classification
Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant that potentiates neurotransmitter activity in the CNS by inhibiting presynaptic reuptake of both serotonin and norepinephrine. 1
Mechanism of Action
The FDA label confirms that venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) are potent inhibitors of neuronal serotonin and norepinephrine reuptake, with weak dopamine reuptake inhibition 1
Venlafaxine demonstrates 30-fold selectivity for serotonin over norepinephrine reuptake, meaning at lower doses it functions more like an SSRI, with noradrenergic effects emerging at higher doses 2
Unlike tricyclic antidepressants, venlafaxine and ODV have no significant affinity for muscarinic, histaminergic, or α-1 adrenergic receptors, which explains its more favorable side effect profile compared to older antidepressants 1
The drug does not possess monoamine oxidase (MAO) inhibitory activity 1
Available Formulations
The American Academy of Child and Adolescent Psychiatry identifies venlafaxine as one of four SNRIs marketed in the United States, available in both immediate-release and extended-release formulations 3
Extended-release venlafaxine allows once-daily dosing and may have a more favorable tolerability profile compared to immediate-release formulations, which require multiple daily doses and cause more peak-trough fluctuations 4
Clinical Applications
Venlafaxine is FDA-approved and effective for major depressive disorder, generalized anxiety disorder, social anxiety disorder, and panic disorder 5
The American Academy of Child and Adolescent Psychiatry notes that SNRIs as a class significantly improve clinician-reported primary anxiety symptoms compared to placebo with high strength of evidence 3
Evidence shows no significant differences in efficacy between various SNRIs or between SNRIs and SSRIs for treating major depressive disorder 4
Common Pitfalls and Safety Considerations
Monitor blood pressure and pulse regularly, as venlafaxine is associated with dose-dependent sustained hypertension and increased pulse, particularly at higher doses 4, 3
Venlafaxine increases bleeding risk through inhibition of platelet serotonin and norepinephrine uptake, particularly when combined with NSAIDs, aspirin, warfarin, or other anticoagulants 3, 6
Never stop venlafaxine abruptly—it requires slow tapering as it is particularly associated with discontinuation syndrome and withdrawal symptoms 3
Common adverse effects include nausea, somnolence/fatigue, dizziness, dry mouth, diaphoresis, headache, tremor, insomnia, decreased appetite, weight loss, and sexual dysfunction 4, 3
Venlafaxine carries a boxed warning for increased suicide risk, particularly in children, adolescents, and young adults 4