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SNRI (Serotonin-Noradrenaline Reuptake Inhibitor) Pregnancy: UK SPC §4.6, verbatim: 'Studies in animals have shown reproductive toxicity at systemic exposure levels (AUC) of duloxetine lower than the maximum clinical exposure. Two large observational studies do not suggest an overall increased risk of major congenital malformation... In the EU study, maternal exposure to duloxetine during late pregnancy (at any time from 20 weeks gestational age to delivery) was associated with an increased risk for preterm birth (less than 2-fold, corresponding to approximately 6 additional premature births per 100 women treated with duloxetine late in pregnancy)... The US observational data have provided evidence of an increased risk (less than 2-fold) of postpartum haemorrhage following duloxetine exposure within the month prior to birth... discontinuation symptoms may occur in the neonate after maternal duloxetine use near term. Discontinuation symptoms seen with duloxetine may include hypotonia, tremor, jitteriness, feeding difficulty, respiratory distress and seizures... Cymbalta should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus.' Breast-feeding: duloxetine is 'very weakly excreted into human milk', an estimated daily infant dose of approximately 0.14% of the maternal dose on a mg/kg basis, but 'As the safety of duloxetine in infants is not known, the use of Cymbalta while breast-feeding is not recommended.'

Duloxetine 30–60mg

Brand names: Cymbalta, Yentreve

Used in: Depression & Anxiety

Duloxetine is a serotonin-noradrenaline reuptake inhibitor (SNRI) used in the orthopaedic setting for chronic musculoskeletal pain and diabetic peripheral neuropathic pain, and at the higher of these doses also for depression and generalised anxiety.

Adult dose

Dose: 30 mg once daily for one week, then increase to 60 mg once daily
Route: Oral — delayed-release capsules (available as 20 mg, 30 mg, 40 mg and 60 mg); swallow whole, do not crush, chew or open
Frequency: Once daily, with or without food
Max: Maximum 60 mg/day for chronic musculoskeletal pain (US label §2 dosage table, 'Maximum Dose' column for Chronic Musculoskeletal Pain)
SCOPE: chronic musculoskeletal pain (the page's primary, ortho-trauma indication) in ADULTS, from the US label. Verbatim §2.6: 'The recommended Duloxetine delayed-release capsules dosage is 60 mg once daily in adults with chronic musculoskeletal pain. Begin treatment at 30 mg once daily for one week, to allow patients to adjust to Duloxetine delayed-release capsules before increasing to 60 mg once daily. There is no evidence that higher dosages confer additional benefit' (the sentence is cut at the source-fetch limit at that point). The §2 dosage table lists Chronic Musculoskeletal Pain as: Starting Dose 30 mg/day, Target Dose 60 mg/day (once daily), Maximum Dose 60 mg/day. The page's 120 mg/day maximum is NOT valid for this indication — 120 mg/day is the UK SPC's ceiling for major depressive disorder, generalised anxiety disorder and diabetic peripheral neuropathic pain ('Dosages above 60 mg once daily, up to a maximum dose of 120 mg per day have been evaluated from a safety perspective in clinical trials'), and the US label caps both diabetic peripheral neuropathic pain and chronic musculoskeletal pain at 60 mg/day. For reference, the UK SPC's other indications: major depressive disorder 60 mg once daily; generalised anxiety disorder 30 mg once daily starting, increased to 60 mg once daily; diabetic peripheral neuropathic pain 60 mg daily. Administration, US §2.1: 'Administer... orally (with or without meals) and swallow whole. Do not chew or crush, and do not open the delayed-release capsule and sprinkle its contents on food or mix with liquids because these actions might affect the enteric coating.' STOPPING, UK SPC §4.2: 'Abrupt discontinuation should be avoided. When stopping treatment with Cymbalta the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions.'

Paediatric dose

Route: Oral
Frequency: Not applicable — no paediatric dose for this indication
No paediatric dose exists for this page's indication, so dosePerKg is null and no weight calculation applies. US label §8.4, verbatim: 'The safety and effectiveness of Duloxetine delayed-release capsules have not been established in pediatric patients with major depressive disorder (MDD), diabetic peripheral neuropathic pain, or chronic musculoskeletal pain.' UK SPC §4.2, verbatim: 'Duloxetine should not be used in children and adolescents under the age of 18 years for the treatment of major depressive disorder because of safety and efficacy concerns. The safety and efficacy of duloxetine for the treatment of generalised anxiety disorder in paediatric patients aged 7-17 years have not been established. The safety and efficacy of duloxetine for the treatment of diabetic peripheral neuropathic pain has not been studied. No data are available.' (The US label does establish paediatric use for generalised anxiety disorder aged 7-17 years and juvenile fibromyalgia aged 13-17 years — different indications from this page, and those regimens are deliberately not reproduced here.) US §8.4 also requires that all paediatric patients on antidepressants be monitored for clinical worsening and emergence of suicidal thoughts and behaviours, with regular monitoring of weight and growth. Verify any use under 18 years against a children's formulary and specialist advice.

Dose adjustments

Renal

UK SPC §4.2, verbatim: 'No dosage adjustment is necessary for patients with mild or moderate renal dysfunction (creatinine clearance 30 to 80 ml/min). Cymbalta must not be used in patients with severe renal impairment (creatinine clearance <30 ml/min; see section 4.3).' §4.4 adds: 'Increased plasma concentrations of duloxetine occur in patients with severe renal impairment on haemodialysis (creatinine clearance <30 ml/min).' The US label separately advises, for diabetic peripheral neuropathic pain, 'consider a lower starting dosage and gradual increase in dosage for patients with renal impairment'.

Hepatic

UK SPC §4.2, verbatim: 'Cymbalta must not be used in patients with liver disease resulting in hepatic impairment', and §4.3 lists 'Liver disease resulting in hepatic impairment' as a contraindication. US label §5.2: 'Hepatotoxicity: Hepatic failure, sometimes fatal, has been reported. Discontinue Duloxetine delayed-release capsules in patients who develop jaundice or other evidence of clinically significant liver dysfunction and should not be resumed unless another cause can be established. Avoid use in patients with substantial alcohol use or evidence of chronic liver disease.'

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to the active substance or to any of the excipients (UK §4.3)
  • Concomitant use with nonselective, irreversible monoamine oxidase inhibitors (UK §4.3). US §4 adds: use of an MAOI within 5 days of stopping duloxetine, starting duloxetine within 14 days of stopping an MAOI, and initiation in patients treated with linezolid or intravenous methylene blue — all because of serotonin syndrome risk
  • Liver disease resulting in hepatic impairment (UK §4.3)
  • Combination with fluvoxamine, ciprofloxacin or enoxacin (potent CYP1A2 inhibitors), 'since the combination results in elevated plasma concentrations of duloxetine' (UK §4.3)
  • Severe renal impairment (creatinine clearance <30 ml/min) (UK §4.3)
  • Initiation in patients with uncontrolled hypertension 'that could expose patients to a potential risk of hypertensive crisis' (UK §4.3)

Side effects

  • Very common (>=1/10) per UK §4.8: headache, somnolence, dizziness, nausea, dry mouth
  • Common (>=1/100 to <1/10) per UK §4.8: decreased appetite, insomnia, agitation, libido decreased, anxiety, abnormal orgasm, abnormal dreams, tremor, paraesthesia, lethargy, blurred vision, tinnitus, palpitations, blood pressure increase, flushing, yawning, constipation, diarrhoea, abdominal pain, vomiting, dyspepsia, flatulence, increased sweating, rash, musculoskeletal pain
  • Uncommon per UK §4.8: suicidal ideation, sleep disorder, bruxism, disorientation, myoclonus, akathisia, nervousness, disturbance in attention, dysgeusia, dyskinesia, restless legs syndrome, mydriasis, visual impairment, vertigo, ear pain, tachycardia, supraventricular arrhythmia (mainly atrial fibrillation), syncope, hypertension, orthostatic hypotension, peripheral coldness, throat tightness, epistaxis, gastrointestinal haemorrhage, gastroenteritis, hepatitis, elevated liver enzymes (ALT, AST, alkaline phosphatase), night sweats, urticaria, contact dermatitis, cold sweat, photosensitivity reactions, increased tendency to bruise, hyperglycaemia (reported especially in diabetic patients), dehydration, hypothyroidism, laryngitis
  • Rare per UK §4.8: anaphylactic reaction, hypersensitivity disorder, hyponatraemia, suicidal behaviour, mania, hallucinations, aggression and anger, serotonin syndrome, convulsion, glaucoma, stress (Takotsubo) cardiomyopathy, hypertensive crisis, acute liver injury, Stevens-Johnson syndrome, angioneurotic oedema, cutaneous vasculitis
  • Very rare / not known per UK §4.8: SIADH, psychomotor restlessness, extrapyramidal symptoms, eosinophilic pneumonia, interstitial lung disease, hepatic failure, jaundice, microscopic colitis
  • US §5 highlights: hepatotoxicity (sometimes fatal hepatic failure); orthostatic hypotension, falls and syncope; serotonin syndrome; increased risk of bleeding, higher with antiplatelet drugs and anticoagulants; severe skin reactions including erythema multiforme and Stevens-Johnson syndrome; activation of mania or hypomania; angle-closure glaucoma
  • US §8.5: SSRIs and SNRIs including duloxetine 'have been associated with clinically significant hyponatremia in geriatric patients', and duloxetine-treated patients reported a higher rate of falls than placebo

Monitoring

  • Blood pressure — UK §4.4: 'in patients with known hypertension and/or other cardiac disease, blood pressure monitoring is recommended, especially during the first month of treatment'; 'For patients who experience a sustained increase in blood pressure while receiving duloxetine either dose reduction or gradual discontinuation should be considered'
  • Do not initiate in uncontrolled hypertension (UK §4.3, §4.4)
  • Liver function — discontinue if jaundice or other evidence of clinically significant liver dysfunction develops (US §5.2)
  • Serotonin syndrome / neuroleptic malignant syndrome, particularly with other serotonergic agents, MAOIs, antipsychotics or other dopamine antagonists (UK §4.4)
  • Mood, suicidal thinking and behaviour, especially in the first months and at dose changes; monitor all paediatric patients on antidepressants, and monitor weight and growth in that group (US §8.4)
  • Watch for mania/hypomania — screen for personal or family history of bipolar disorder, mania or hypomania before initiating (US §5.8); use with caution in patients with a history of mania, bipolar disorder and/or seizures (UK §4.4)
  • Intraocular pressure risk — mydriasis has been reported, so caution in patients with increased intraocular pressure or at risk of acute narrow-angle glaucoma (UK §4.4)
  • On stopping, taper over at least one to two weeks and watch for withdrawal reactions; 'If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered' (UK §4.2)

Clinical monograph

How it works

It potentiates descending inhibitory pain pathways and central monoaminergic neurotransmission by inhibiting reuptake of serotonin and noradrenaline.

Prescribing in practice

  • Do not stop abruptly — taper to avoid a discontinuation syndrome of dizziness, paraesthesia, anxiety and sleep disturbance.
  • Avoid combining with MAOIs and use caution with other serotonergic drugs (triptans, tramadol, SSRIs) because of serotonin syndrome risk.
  • Contraindicated in uncontrolled hypertension and significant hepatic impairment; can raise blood pressure and is not recommended in severe renal impairment.

Monitoring

Monitor blood pressure, mood and for emergent suicidal ideation early in treatment or after dose changes.

Counselling the patient

  • Pain benefit may take a couple of weeks to build up.
  • Do not stop suddenly; speak to your prescriber about reducing gradually.
  • Report worsening mood, agitation or thoughts of self-harm.

Evidence & guidelines

NICE recommends duloxetine as a first-line option for neuropathic pain and for chronic primary pain in adults.

Reference: NICE NG226 (Osteoarthritis 2022); NICE NG59 (Low Back Pain 2016); NICE NG193 (Neuropathic Pain); Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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