SNRIs and NRIs — cross-table viva · Psych Vivas

Prompt

Examiner draws columns: Agent / Transporters / Start dose / Killer monitoring. Cards: Blier/Debonnel dose map, Thase BP meta, Thase remission meta, STAR*D switch, Cipriani 2018, Detke duloxetine 60 mg, Gelenberg venlafaxine GAD, Eyding reboxetine, Hunter criteria, Schatzberg discontinuation, Movig hyponatraemia, Montejo sexual SE.

Station structure

Time: 8–10 minutes. Depth: consultant teaching registrar. Expect mechanism → dose → trial name → safety without dual-action marketing slogans.[1][5]

Core questions and model points

Define SNRI vs selective NRI. SNRI = SERT+NET (venlafaxine, desvenlafaxine, duloxetine, milnacipran class). Selective NRI = NET-preferential (reboxetine; atomoxetine for ADHD). Do not call reboxetine an SNRI.[1][9]
Venlafaxine dual-action mantra. Low dose mainly SERT; higher doses recruit NET — Blier 2007 and Debonnel 2007.[1][2]
Doses. Venlafaxine XR often 75 → 150–225 mg; desvenlafaxine commonly 50 mg; duloxetine 30–60 → 60–120 mg; state product-label humility.[7]
BP. Thase 1998 meta: venlafaxine BP effects — check baseline and after titration.[6]
STAR*D switch. After SSRI failure, venlafaxine-XR ≈ bupropion-SR ≈ sertraline for remission — choose by patient factors.[4]
Thase remission meta vs Cipriani. Historical venlafaxine remission edge over SSRIs; modern NMA shows class efficacy with modest between-drug differences — no blanket SNRI supremacy.[3][5]
GAD. Gelenberg JAMA 2000: venlafaxine XR vs placebo in nondepressed GAD over 6 months.[8]
Duloxetine. Detke 60 mg once daily MDD RCT; pain/painful-symptom niche in viva stems.[7]
Reboxetine / Eyding. Unpublished data reverse published efficacy story — ineffective/potentially harmful overall; publication bias teaching point.[9]
Toxicity and stop rules. Hunter criteria for serotonin toxicity; never irreversible MAOI + SNRI; venlafaxine discontinuation counselling (short half-life).[10]

Killer fails

Claiming dual action at every venlafaxine dose.[1]
Combining SNRI with MAOI without washout.[10]
Ignoring BP on titration.[6]
Defending reboxetine with only published industry-era claims post-Eyding.[9]

References

[1]Blier P, Saint-André E, Hébert C, et al. Effects of different doses of venlafaxine on serotonin and norepinephrine reuptake in healthy volunteers Int J Neuropsychopharmacol, 2007.PMID 16690005
[2]Debonnel G, Saint-André E, Hébert C, et al. Differential physiological effects of a low dose and high doses of venlafaxine in major depression Int J Neuropsychopharmacol, 2007.PMID 16690006
[3]Thase ME, Entsuah AR, Rudolph RL Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors Br J Psychiatry, 2001.PMID 11230034
[4]Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression N Engl J Med, 2006.PMID 16554525
[5]Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis Lancet, 2018.PMID 29477251
[6]Thase ME Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients J Clin Psychiatry, 1998.PMID 9818630
[7]Detke MJ, Lu Y, Goldstein DJ, et al. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial J Clin Psychiatry, 2002.PMID 12000204
[8]Gelenberg AJ, Lydiard RB, Rudolph RL, et al. Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: a 6-month randomized controlled trial JAMA, 2000.PMID 10865302
[9]Eyding D, Lelgemann M, Grouven U, et al. Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials BMJ, 2010.PMID 20940209
[10]Dunkley EJ, Isbister GK, Sibbritt D, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity QJM, 2003.PMID 12925718

Core questions and model points

Define SNRI vs selective NRI. SNRI = SERT+NET (venlafaxine, desvenlafaxine, duloxetine, milnacipran class). Selective NRI = NET-preferential (reboxetine; atomoxetine for ADHD). Do not call reboxetine an SNRI.[1][9]

Venlafaxine dual-action mantra. Low dose mainly SERT; higher doses recruit NET — Blier 2007 and Debonnel 2007.[1][2]

Doses. Venlafaxine XR often 75 → 150–225 mg; desvenlafaxine commonly 50 mg; duloxetine 30–60 → 60–120 mg; state product-label humility.[7]

BP. Thase 1998 meta: venlafaxine BP effects — check baseline and after titration.[6]

STAR*D switch. After SSRI failure, venlafaxine-XR ≈ bupropion-SR ≈ sertraline for remission — choose by patient factors.[4]

Thase remission meta vs Cipriani. Historical venlafaxine remission edge over SSRIs; modern NMA shows class efficacy with modest between-drug differences — no blanket SNRI supremacy.[3][5]

GAD. Gelenberg JAMA 2000: venlafaxine XR vs placebo in nondepressed GAD over 6 months.[8]

Duloxetine. Detke 60 mg once daily MDD RCT; pain/painful-symptom niche in viva stems.[7]

Reboxetine / Eyding. Unpublished data reverse published efficacy story — ineffective/potentially harmful overall; publication bias teaching point.[9]

Toxicity and stop rules. Hunter criteria for serotonin toxicity; never irreversible MAOI + SNRI; venlafaxine discontinuation counselling (short half-life).[10]

Killer fails

Claiming dual action at every venlafaxine dose.[1]

Combining SNRI with MAOI without washout.[10]

Ignoring BP on titration.[6]

Defending reboxetine with only published industry-era claims post-Eyding.[9]

References

[1]Blier P, Saint-André E, Hébert C, et al. Effects of different doses of venlafaxine on serotonin and norepinephrine reuptake in healthy volunteers Int J Neuropsychopharmacol, 2007.PMID 16690005
[2]Debonnel G, Saint-André E, Hébert C, et al. Differential physiological effects of a low dose and high doses of venlafaxine in major depression Int J Neuropsychopharmacol, 2007.PMID 16690006
[3]Thase ME, Entsuah AR, Rudolph RL Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors Br J Psychiatry, 2001.PMID 11230034
[4]Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression N Engl J Med, 2006.PMID 16554525
[5]Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis Lancet, 2018.PMID 29477251
[6]Thase ME Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients J Clin Psychiatry, 1998.PMID 9818630
[7]Detke MJ, Lu Y, Goldstein DJ, et al. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial J Clin Psychiatry, 2002.PMID 12000204
[8]Gelenberg AJ, Lydiard RB, Rudolph RL, et al. Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: a 6-month randomized controlled trial JAMA, 2000.PMID 10865302
[9]Eyding D, Lelgemann M, Grouven U, et al. Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials BMJ, 2010.PMID 20940209
[10]Dunkley EJ, Isbister GK, Sibbritt D, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity QJM, 2003.PMID 12925718