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SNRI (Serotonin-Noradrenaline Reuptake Inhibitor)

Duloxetine 30–60mg

Brand names: Cymbalta, Yentreve

Adult dose

Dose: 30mg once daily for 1–2 weeks, then increase to 60mg once daily
Route: Oral
Frequency: Once daily (morning preferred)
Max: 120mg/day (in divided doses for neuropathic pain)
For chronic musculoskeletal pain (osteoarthritis, chronic low back pain) and neuropathic pain. NICE NG59 (low back pain): duloxetine as adjunct in chronic LBP. Also licensed for diabetic peripheral neuropathic pain, GAD, and major depressive disorder.

Paediatric dose

Route: Oral
Frequency: N/A
Max: Not licensed <18 years for pain indications (MDD licence from 7 years in some countries)
Not recommended for musculoskeletal or neuropathic pain in children. Specialist use only if considered for depression in adolescents.

Dose adjustments

Renal

Avoid if eGFR <30 — duloxetine and metabolites accumulate; increased nausea and adverse effects

Hepatic

Avoid in hepatic impairment (Child-Pugh B/C) — significantly reduced clearance

Clinical pearls

  • NICE NG226 (Osteoarthritis 2022): duloxetine recommended for knee and hip OA with moderate-to-severe pain inadequately controlled by other analgesics
  • NICE NG59 (Chronic Low Back Pain): duloxetine is one of the few pharmacological options recommended for chronic LBP
  • Nausea in first 2 weeks: counsel patient to persist — most resolves; taking with food helps
  • Taper off slowly when stopping — abrupt withdrawal causes discontinuation syndrome (dizziness, nausea, electric shock sensations, irritability)
  • Evidence base: COMBO trial (hip/knee OA), CMBAX trial (low back pain) — NNT approximately 5 for ≥30% pain reduction

Contraindications

  • Concurrent MAOI use (within 14 days)
  • Uncontrolled narrow-angle glaucoma
  • Severe renal impairment (eGFR <30)
  • Hepatic impairment

Side effects

  • Nausea (most common — first 1–2 weeks)
  • Dry mouth
  • Dizziness
  • Fatigue
  • Constipation
  • Increased sweating
  • Hypertension (monitor BP)
  • Suicidal ideation (rare — MHRA warning, especially in young adults under 25)

Interactions

  • MAOIs — contraindicated; serotonin syndrome
  • Tramadol/other SNRIs — serotonin syndrome risk
  • Warfarin — increased bleeding risk (monitor INR)
  • CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) — increase duloxetine levels
  • CYP1A2 inducers (smoking) — reduce duloxetine levels

Monitoring

  • Blood pressure (baseline and at dose changes)
  • Pain scores at 4–8 weeks (efficacy assessment)
  • Mood and suicidal ideation (MHRA warning in young adults)
  • Renal and hepatic function before starting

Reference: BNFc; BNF; NICE NG226 (Osteoarthritis 2022); NICE NG59 (Low Back Pain 2016); NICE NG193 (Neuropathic Pain). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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