SNRI (Serotonin-Norepinephrine Reuptake Inhibitor)
Enhances serotonergic and noradrenergic activity in the prefrontal cortex by inhibiting the reuptake of serotonin and norepinephrine; at lower doses it primarily affects serotonin, while higher doses also engage norepinephrine reuptake inhibition. Dopaminergic effects in the prefrontal cortex have also been observed at higher doses, possibly contributing to energy and motivation enhancement.
Major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder, social anxiety disorder (SoAD)
Premenstrual dysphoric disorder (PMDD), posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), neuropathic pain, fibromyalgia, migraine prophylaxis, post-stroke depression (PSD), depression in Parkinson’s disease (PD)
Oral immediate-release and extended-release capsules/tablets
37.5 mg p.o. daily, titrated in 37.5–75 mg increments every 4–7 days as tolerated
75–375 mg/day
Half-life ~5 hours (IR) and ~15 hours (XR); metabolized by CYP2D6 to active metabolite (O-desmethylvenlafaxine); steady state reached in ~3 days
Nausea, dizziness, insomnia, dry mouth, diaphoresis, weight loss, constipation, sexual dysfunction, and dose-dependent increases in blood pressure
Hypertension (especially >150 mg/day), serotonin syndrome, SIADH, angle-closure glaucoma, withdrawal symptoms with abrupt cessation
Monitor blood pressure regularly, particularly at doses > 150 mg/day. Assess for suicidality and withdrawal symptoms during discontinuation or missed doses.
Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders
Venlafaxine requires dose adjustments in patients with renal or hepatic impairment, with reductions of 25–50% recommended. In individuals with seizure disorders or traumatic brain injury (TBI), venlafaxine may lower the seizure threshold, particularly at higher doses. Older adults may be more prone to orthostatic hypotension and should begin at lower doses with slow titration.