SNRIs · Psychiatry
Duloxetine
Cymbalta®(brand names vary by market)
An antidepressant that also treats the pain, which is often the reason it is chosen.
Also: modified release
Mechanism
Serotonin and noradrenaline reuptake inhibition, with the noradrenergic component contributing to descending inhibition of pain signalling in the spinal cord.
Open the interactive pathwayIndications
- Major depressive disorder
- Generalised anxiety disorder
- Diabetic peripheral neuropathic pain
- Fibromyalgia
- Chronic musculoskeletal pain
Formulations
Dosing concepts
Two conditions, one drug
In a depressed patient with painful diabetic neuropathy it treats both, which is a real prescribing advantage and a common reason for the choice.
Blood pressure
The noradrenergic effect raises blood pressure modestly and dose-dependently, so it is measured rather than assumed.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- ~50%
- Half-life
- ~12 h
- Elimination
- hepatic: CYP1A2 and CYP2D6; smoking induces CYP1A2 and lowers levels appreciably
- Protein binding
- >90%
Adverse effects
- NauseacommonThe commonest early complaint and usually transient.
- Dry mouth, constipationcommon
- Raised blood pressurecommon & serious
- HepatotoxicityseriousAvoided in significant alcohol use and chronic liver disease.
- Discontinuation syndromecommonProminent with this agent: dizziness, electric-shock sensations, irritability.
- Hyponatremiaserious
Contraindications & precautions
Contraindications
- Concurrent or recent MAO inhibitor
- Uncontrolled narrow-angle glaucoma
- Severe hepatic impairment
- Creatinine clearance below about 30 mL/min
Precautions
- Hypertension
- Alcohol use or liver disease
- Bleeding risk
- Bipolar disorder
Interactions
- SSRIs / SNRIs + MAO inhibitors (including linezolid)avoidSerotonin syndrome: agitation, clonus, hyperthermia: potentially fatal.
- SSRIs / SNRIs + TramadolcautionSerotonin syndrome (usually milder spectrum) and seizures, especially at higher doses or in the elderly.
- SSRIs + NSAIDs / anticoagulantsmonitorUpper GI bleeding risk roughly doubles versus either alone.
Monitoring
Blood pressure
It rises dose-dependently and is easy to overlook in a psychiatric review · Baseline and after dose increases
Mood, pain score and function
Both indications need judging
Liver enzymes if symptomatic or drinking
Hepatotoxicity
Counselling points
- Swallow capsules whole; do not open or crush them.
- Nausea is common in the first week or two and usually settles.
- Never stop it abruptly: the withdrawal from this one is notably unpleasant.
- Avoid heavy alcohol use.
- We will check your blood pressure at reviews.
Clinical pearls
- Discontinuation symptoms are worse with the shorter-acting serotonergic drugs, and duloxetine and paroxetine are the two patients most often describe as impossible to stop. Planning the taper at the start prevents that conversation later.
- For painful diabetic neuropathy it is one of the few agents with genuine evidence, which is why it appears on both a psychiatry and a diabetes formulary.
References & review
- Duloxetine product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.