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Psych TopicsPsychopharmacology — SNRIs and NRIs

Psych · Psychopharmacology — SNRIs and NRIs

SNRIs and norepinephrine reuptake inhibitors

Also known as Venlafaxine · Desvenlafaxine · Duloxetine · Milnacipran · Levomilnacipran · Reboxetine · Atomoxetine · Dual reuptake inhibitors · Selective norepinephrine reuptake inhibitors

Exam-exhaustive fellowship pharmacology of SNRIs and selective NRIs — venlafaxine dose-dependent SERT/NET occupancy, desvenlafaxine, duloxetine depression and pain licences, milnacipran class, reboxetine publication-bias evidence, atomoxetine as ADHD NRI pointer, BP monitoring, discontinuation, hyponatraemia, serotonin toxicity, STAR*D switch and Cipriani ranking humility. FRANZCP-primary, globally tagged.

high20 referencesUpdated 26 July 202612 min readVerification in progress

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FRANZCPMRCPsychABPNMD-DNBNEET-SS

Red flags

  • Irreversible MAOI plus SNRI (or within washout) — serotonin toxicity pathway; never improvise
  • Sustained BP rise or hypertensive urgency after venlafaxine/desvenlafaxine titration — hold/reduce and investigate, do not keep escalating
  • Fever, clonus, hyperreflexia, agitation on serotonergic combinations — treat as serotonin toxicity
  • Confusion, falls or seizures in an older adult on SNRI — check sodium urgently
  • Jaundice, dark urine or marked LFT rise on duloxetine — stop and assess hepatic injury; alcohol risk compounds harm
  • Electric-shock sensations, dizziness and flu-like symptoms after missed venlafaxine doses — discontinuation syndrome, not 'addiction drama'; plan a taper
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Your progress

Saved on this device.

Practise this topic10 MCQs with explanations

Target exams

FRANZCPMRCPsychABPNMD-DNBNEET-SS

Red flags

  • Irreversible MAOI plus SNRI (or within washout) — serotonin toxicity pathway; never improvise
  • Sustained BP rise or hypertensive urgency after venlafaxine/desvenlafaxine titration — hold/reduce and investigate, do not keep escalating
  • Fever, clonus, hyperreflexia, agitation on serotonergic combinations — treat as serotonin toxicity
  • Confusion, falls or seizures in an older adult on SNRI — check sodium urgently
  • Jaundice, dark urine or marked LFT rise on duloxetine — stop and assess hepatic injury; alcohol risk compounds harm
  • Electric-shock sensations, dizziness and flu-like symptoms after missed venlafaxine doses — discontinuation syndrome, not 'addiction drama'; plan a taper
The one-line answer

An SNRI blocks SERT and NET; a selective NRI blocks NET alone. The single most testable fact is that venlafaxine's "dual action" is dose-dependent — serotonergic first, noradrenergic as you climb — so you prescribe with blood-pressure monitoring, duloxetine liver literacy, discontinuation planning, and the 2-6-2 discipline the class shares, and you treat the reboxetine marketing story through the Eyding publication-bias lens, not nostalgia.[1][5][11][13]

Meet the patient

A 52-year-old building supervisor started venlafaxine XR 75 mg for a first depressive episode with fatigue and poor concentration. Six weeks in, mood is lifting; the dose was pushed to 225 mg when energy lagged. At this review his GP noted BP 158/98 — previously 124/78 — and the practice nurse wonders whether to start an antihypertensive.[1][13]

The BP is not a new hypertension diagnosis to chase with a second drug. It is the venlafaxine tax: a dose-related noradrenergic effect on diastolic pressure in a minority, exactly the signal Thase quantified across thousands of trial patients. The right move is to hold or reduce the dose and recheck, not to layer amlodipine on top of a fixable cause.[13]

This leaf deepens the antidepressant class page on the dual-reuptake and noradrenergic agents. The exam question is never "is an SNRI stronger than an SSRI?" — it is "at what dose, with what monitoring, and what will it do to the blood pressure and the liver?"[1][5][19]

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References20ShowHide
  1. [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. [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. [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. [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. [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. [6]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
  7. [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. [8]Goldstein DJ, Mallinckrodt C, Lu Y, et al. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial J Clin Psychiatry, 2002.PMID 11926722
  9. [9]Perahia DG, Pritchett YL, Desaiah D, et al. Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect? Int Clin Psychopharmacol, 2006.PMID 17012978
  10. [10]Liebowitz MR, Manley AL, Padmanabhan SK, et al. Efficacy, safety, and tolerability of desvenlafaxine 50 mg/day and 100 mg/day in outpatients with major depressive disorder Curr Med Res Opin, 2008.PMID 18507895
  11. [11]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
  12. [12]Michelson D, Allen AJ, Busner J, et al. Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study Am J Psychiatry, 2002.PMID 12411225
  13. [13]Thase ME Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients J Clin Psychiatry, 1998.PMID 9818630
  14. [14]Schatzberg AF, Blier P, Delgado PL, et al. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research J Clin Psychiatry, 2006.PMID 16683860
  15. [15]Movig KL, Leufkens HG, Lenderink AW, et al. Association between antidepressant drug use and hyponatraemia: a case-control study Br J Clin Pharmacol, 2002.PMID 11966666
  16. [16]Montejo AL, Llorca G, Izquierdo JA, et al. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients J Clin Psychiatry, 2001.PMID 11229449
  17. [17]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
  18. [18]Boyer EW, Shannon M The serotonin syndrome N Engl J Med, 2005.PMID 15784664
  19. [19]Malhi GS, Bell E, Bassett D, et al. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders Aust N Z J Psychiatry, 2021.PMID 33353391
  20. [20]Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments Can J Psychiatry, 2016.PMID 27486148

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