Understand SNRIs Better: Duloxetine and Venlafaxine

Get a Grip on SNRIs: A Deep Dive into Duloxetine and Venlafaxine dosing
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The video explains the concept of sequential binding in SNRIs (serotonin and norepinephrine reuptake inhibitors) like duloxetine (Cymbalta) and venlafaxine (Effexor). SNRIs block the serotonin transporter (SERT) and norepinephrine transporter (NET), but they don't bind to both simultaneously. Instead, they bind to the receptor with the highest affinity first, and then move on to the next receptor.

For Effexor, SERT is maxed out at around 75mg, and NET doesn't kick in until around 150mg. Below 75mg, it acts like an SSRI. For significant norepinephrine reuptake inhibition, doses of 225-375mg are required. At very high doses above 375mg, dopamine reuptake blockade may also occur.

Cymbalta has a more balanced affinity for SERT and NET, so there is more spillover to NET at lower doses. Studies suggest SERT and NET blockade may occur at 40-60mg for Cymbalta. However, doses above 60mg haven't shown increased efficacy for neuropathic pain or fibromyalgia, while some patients may require up to 120mg for severe depression.

The key takeaway is that there is significant variability across individuals, but for SNRIs to have different or better effects than SSRIs, higher doses are required to engage the norepinephrine component.

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#depression #snri #psychopharmacology

0:00 Space Intro
0:11 Understand SNRIs
0:31 SNRI MOA Review
1:12 SNRI Fountain
2:11 Dosing Time (Cymbalta and Effexor)
2:48 Venlafaxine Dosing
4:22 Dose Response Curves
4:40 Duloxetine Dosing
6:06 Space Outro