Equivalent Dosing: Venlafaxine to Duloxetine
There is no established direct milligram-to-milligram conversion between Effexor (venlafaxine) 175mg and Cymbalta (duloxetine), but the standard therapeutic target dose of duloxetine 60mg once daily is appropriate when switching from venlafaxine 175mg, as both medications are SNRIs with similar mechanisms of action but different potencies. 1, 2
Understanding the Pharmacological Differences
Venlafaxine and duloxetine are not equivalent on a milligram basis because they have fundamentally different binding affinities and potencies at the serotonin and norepinephrine transporters 2
Venlafaxine is a relatively weak SNRI with a 30-fold difference in serotonin versus norepinephrine transporter binding, meaning it acts more like an SSRI at lower doses and only engages norepinephrine reuptake inhibition at higher doses (typically above 150mg/day) 2
Duloxetine is a more potent and balanced SNRI with approximately 10:1 serotonin to norepinephrine transporter binding, providing dual action even at lower doses 2
Venlafaxine 175mg represents a moderate-to-high dose with significant norepinephrine activity, while duloxetine 60mg once daily provides comparable dual neurotransmitter effects despite the lower milligram amount 1, 2
Recommended Switching Strategy
Start duloxetine at 30mg once daily for one week, then increase to 60mg once daily to minimize nausea and improve tolerability 1, 3, 4
The 60mg once daily dose is the standard therapeutic target for duloxetine across most indications including depression and neuropathic pain 1, 3
If needed for adequate response, duloxetine can be increased to 60mg twice daily (120mg/day maximum), though most patients achieve therapeutic benefit at 60mg once daily 1, 3
When switching from venlafaxine 175mg, you can either cross-taper (gradually reducing venlafaxine while introducing duloxetine) or perform a direct switch to duloxetine 60mg once daily, as immediate switching has been shown to be well-tolerated 5
Clinical Considerations During the Switch
Taking duloxetine with food significantly reduces nausea, particularly when starting at the 60mg dose rather than 30mg 4
The most common adverse effects when initiating duloxetine include nausea (which can be mitigated by the 30mg starting dose for one week), dry mouth, headache, dizziness, and constipation 2, 6
Monitor blood pressure during the transition, as both venlafaxine at 175mg and duloxetine can cause modest blood pressure elevations, though duloxetine typically produces less hypertension than higher-dose venlafaxine 1, 2, 6
Venlafaxine has a short half-life (5 hours for parent compound, 12 hours for active metabolite), so taper venlafaxine gradually over 2-4 weeks if cross-tapering to avoid withdrawal symptoms 2
Dosing Algorithm
For patients currently on venlafaxine 175mg:
Week 1: Start duloxetine 30mg once daily (with food) while continuing venlafaxine 175mg, or begin tapering venlafaxine to 150mg 7, 4
Week 2: Increase duloxetine to 60mg once daily and continue reducing venlafaxine (e.g., to 75-112.5mg) 7, 3
Weeks 3-4: Maintain duloxetine 60mg once daily and complete venlafaxine taper 7
Week 6-8: Assess response; if inadequate, consider increasing duloxetine to 90mg or 120mg daily 1, 6