duloxetine
Serotonin-norepinephrine reuptake inhibitor· Brands: Cymbalta, YentrevePO
Mechanism of action
Duloxetine inhibits the reuptake of serotonin and norepinephrine by blocking their respective transporters, thereby increasing the concentrations of these neurotransmitters in the synaptic cleft. This action is thought to underlie its efficacy in mood disorders and pain modulation.
Pharmacokinetics
Duloxetine is well absorbed after oral administration, reaching peak plasma concentrations in about 6 hours. It is extensively metabolized in the liver, primarily via CYP1A2 and CYP2D6, with an elimination half-life of approximately 12 hours. Metabolites are excreted mainly in urine.
Indications & dosing
Major depressive disorder
Start 30 mg once daily, increase to 60 mg if tolerated. Maximum 120 mg/day in divided doses or as single dose.
- adult · PO: 30–60 mg once daily · Start 30 mg once daily, increase to 60 mg if tolerated. Maximum 120 mg/day in divided doses or as single dose.
Generalized anxiety disorder
Initial 30 mg once daily, titrate to 60 mg. Maximum 120 mg/day.
- adult · PO: 30–60 mg once daily · Initial 30 mg once daily, titrate to 60 mg. Maximum 120 mg/day.
Diabetic peripheral neuropathic pain
Start 60 mg once daily; may increase to 120 mg/day if needed.
- adult · PO: 60–120 mg once daily · Start 60 mg once daily; may increase to 120 mg/day if needed.
Fibromyalgia
Initiate 30 mg once daily for 1 week, then increase to 60 mg. Maximum 120 mg/day.
- adult · PO: 30–60 mg once daily · Initiate 30 mg once daily for 1 week, then increase to 60 mg. Maximum 120 mg/day.
Chronic musculoskeletal pain
Doses up to 120 mg/day have been used; start low and titrate.
- adult · PO: 30–60 mg once daily · Doses up to 120 mg/day have been used; start low and titrate.
Stress urinary incontinence (moderate to severe)off-label
Licensed in some countries; check local formulary. Reduce dose in renal impairment.
- adult · PO: 40 mg twice daily · Licensed in some countries; check local formulary. Reduce dose in renal impairment.
Contraindications & precautions
- Concomitant use with monoamine oxidase inhibitors (MAOIs) within 14 days · Can cause serotonin syndrome; allow 14 days after stopping MAOI before starting duloxetine.
- Uncontrolled narrow-angle glaucoma · Duloxetine can increase intraocular pressure.
- Severe hepatic impairment (Child-Pugh class C) · Avoid in patients with hepatic insufficiency; duloxetine is extensively metabolised by the liver.
- Known hypersensitivity to duloxetine or any component of the product · Cross-sensitivity with other SNRIs may occur.
- Severe renal impairment (creatinine clearance < 30 mL/min) · Use with caution; reduced renal function may increase duloxetine exposure.
- Monitor liver function tests, especially in patients with hepatic impairment or alcohol use.
- Do not discontinue abruptly; taper the dose to avoid withdrawal symptoms.
- Use with caution with other serotonergic drugs (e.g., SSRIs, triptans) to reduce risk of serotonin syndrome.
- Monitor blood pressure, as duloxetine may increase blood pressure in some patients.
- Assess for worsening of depression or emergence of suicidal thoughts, particularly in young adults.
Adverse effects
- Nausea
- Dry mouth
- Somnolence
- Dizziness
- Insomnia
- Constipation
- Serotonin syndromeserious
- Hepatotoxicityserious
- Hyponatremiaserious
- Increased bleeding riskserious
Renal & hepatic adjustment
- eGFR 30–59: Use with caution. Consider lower starting dose (30 mg once daily) and maximum 60 mg daily.
- eGFR 0–29: Contraindicated due to increased risk of adverse events. (avoid)
- Hepatic impairment (mild): Use with caution; monitor liver function. No specific dose adjustment required.
- Hepatic impairment (moderate): Reduce starting dose to 30 mg once daily; use with caution. Consider maximum 60 mg daily.
- Hepatic impairment (severe): Avoid use due to increased risk of hepatotoxicity. (avoid)
Monitoring, pregnancy & toxicity
- Blood pressure and heart rate · At baseline and regularly during treatment
- Liver function tests · At baseline and periodically, especially if symptoms of hepatic dysfunction occur
- Mood and suicidal ideation · At initiation and during treatment, especially in youth
- Signs of serotonin syndrome · During treatment, especially when co-administered with other serotonergic drugs
- Symptoms of hyponatraemia · During treatment, especially in elderly
- Pregnancy: Use only if clearly needed, as data on use in pregnancy are limited. In the third trimester, neonatal complications may occur, including respiratory distress, poor feeding, and withdrawal syndrome. Consider the risk of untreated depression.
- Toxicity: Serotonin syndrome (agitation, hyperthermia, flushing, hyperreflexia) · Discontinue duloxetine, provide supportive care, and administer antiserotonergic agents if severe.
- Toxicity: CNS effects: drowsiness, coma, convulsions · Supportive care, maintain airway, ventilate if necessary, treat seizures with benzodiazepines.
- Toxicity: Cardiovascular effects: tachycardia, hypertension · Monitor vital signs, treat hypertension with short-acting antihypertensives if needed.
- Toxicity: GI effects: nausea, vomiting · Supportive care, monitor fluids and electrolytes.
Clinical notes
Duloxetine is indicated for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, and fibromyalgia. It is usually taken once daily with or without food. Gradual dose reduction is advised on discontinuation to avoid withdrawal symptoms. Monitor patients for worsening depression or suicidal ideation, especially at the start of therapy.
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BNF; local formulary