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SNRI (Serotonin-Noradrenaline Reuptake Inhibitor) Pregnancy: Avoid if possible — limited data. Neonatal abstinence syndrome reported. Discuss risk-benefit; sertraline preferred.

Duloxetine

Brand names: Cymbalta, Yentreve

Adult dose

Dose: Depression / GAD: 60mg OD (or 30mg OD for 2 weeks initially then 60mg OD). Neuropathic pain (diabetic peripheral neuropathy): 60mg OD. Fibromyalgia: 30mg OD initially, increase to 60mg OD after 1 week. Stress urinary incontinence (Yentreve): 40mg BD.
Route: Oral (enteric-coated capsule — do not crush)
Frequency: Once daily (depression/neuropathic pain) or twice daily (stress incontinence)
Max: 120mg OD (depression/GAD); 60mg OD (neuropathic pain, fibromyalgia); 40mg BD (stress incontinence)
Do not open or crush enteric-coated capsule — irritant to gastric mucosa. Take with or without food. Avoid if eGFR <30. Withdrawal syndrome similar to venlafaxine — taper slowly. NICE recommends for diabetic peripheral neuropathy as one of four first-line options.

Paediatric dose

Route: Oral
Frequency: Once daily
Max: Not applicable
Not licensed under 18 years in UK. Seek specialist child and adolescent psychiatry opinion.

Dose adjustments

Renal

eGFR <30: avoid — active metabolites accumulate.

Hepatic

Avoid in hepatic impairment — significant hepatic metabolism; risk of hepatotoxicity.

Clinical pearls

  • NICE NG59: duloxetine is one of four first-line drugs for diabetic peripheral neuropathy (alongside amitriptyline, pregabalin, gabapentin) — significant evidence base beyond psychiatry
  • Hepatotoxicity: rare but fatalities reported — avoid in heavy alcohol users; check LFTs if abdominal symptoms develop
  • Blood pressure: noradrenergic effect raises BP — check BP before and during treatment, especially in patients with hypertension
  • Fibromyalgia: FDA-approved indication; reduces pain, fatigue, and functional disability

Contraindications

  • eGFR <30
  • Hepatic impairment
  • Uncontrolled narrow-angle glaucoma
  • MAOIs (within 14 days — serotonin syndrome)
  • Hypersensitivity to duloxetine

Side effects

  • Nausea (common at initiation)
  • Dry mouth, constipation
  • Fatigue, somnolence
  • Sexual dysfunction
  • Sweating
  • Hepatotoxicity (rare but serious — monitor LFTs if hepatic risk factors)
  • Hypertension (noradrenergic effect — check BP)
  • Urinary hesitancy
  • Hyponatraemia (SIADH)

Interactions

  • MAOIs — contraindicated (serotonin syndrome; 14-day washout)
  • CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) — increase duloxetine levels significantly; avoid
  • CYP2D6 inhibitors (paroxetine, fluoxetine) — increase duloxetine exposure; monitor
  • Warfarin — increased bleeding risk; monitor INR

Monitoring

  • Blood pressure (baseline and periodic)
  • LFTs (if hepatic risk factors or symptoms)
  • Mood and suicidality
  • Sodium in elderly

Reference: BNFc; BNF 90; NICE NG59 (Neuropathic Pain); NICE CG90 (Depression). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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