Venlafaxine Drug Classification
Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI), also referred to as a selective serotonin-norepinephrine reuptake inhibitor (SSNRI). 1, 2
Mechanism of Action
Venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) are potent inhibitors of neuronal serotonin and norepinephrine reuptake, with weak dopamine reuptake inhibition. 2
The drug exhibits approximately 30-fold selectivity for serotonin over norepinephrine reuptake at lower doses. 3
Venlafaxine begins to meaningfully inhibit norepinephrine reuptake only at doses of 225 mg/day or higher, while it potently inhibits serotonin reuptake across its entire therapeutic range starting at 75 mg/day. 4
Unlike tricyclic antidepressants, venlafaxine has no significant affinity for muscarinic, histaminergic, or α-1 adrenergic receptors and does not possess monoamine oxidase (MAO) inhibitory activity. 2
SNRI Class Membership
The SNRI class currently includes four medications marketed in the United States: venlafaxine (immediate-release and extended-release formulations), desvenlafaxine, duloxetine, and milnacipran. 5
Venlafaxine is available in both short-acting and extended-release preparations, with the extended-release formulation allowing once-daily dosing due to its sufficiently long elimination half-life. 1, 5
Clinical Context
Guidelines classify venlafaxine as an SSNRI alongside duloxetine for first-line treatment of neuropathic pain, distinguishing it from selective serotonin reuptake inhibitors (SSRIs). 1
The dual mechanism of inhibiting both serotonin and norepinephrine reuptake differentiates SNRIs from SSRIs, which selectively target only serotonin reuptake. 5, 3