Rankings / Mood, Anxiety & Stress
SNRIs (venlafaxine / duloxetine)
Mood, Anxiety & Stress · Dual SERT/NET reuptake inhibitor
Tier B
What this is
Useful when depression coexists with pain or fatigue. Venlafaxine discontinuation can be particularly severe — taper cautiously, sometimes cross-titrate to fluoxetine. Duloxetine has FDA pain indications (diabetic neuropathy, fibromyalgia, chronic musculoskeletal pain). A 2025 systematic review/meta-analysis quantified increased GI bleeding risk for serotonergic antidepressants, and observational data link SNRIs to fall-related hospitalizations in older adults.
Mechanism
Block both serotonin and norepinephrine reuptake; pain and fatigue indications in addition to depression/anxiety; venlafaxine primarily serotonergic at low doses, adds norepinephrine >150 mg
Dose & route
Venlafaxine 37.5-300 mg XR; duloxetine 30-120 mg PO daily
Citations
- https://pubmed.ncbi.nlm.nih.gov/29477251/
- https://pubmed.ncbi.nlm.nih.gov/17472803/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3131098/
- https://pubmed.ncbi.nlm.nih.gov/41461139/
- https://doi.org/10.3389/fpsyt.2026.1756085
- https://doi.org/10.71350/jclp.31
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This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.