Duloxetine: Difference between revisions

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| pregnancy = Category C

| legal = Rx-only

| intro = '''Duloxetine''' is a serotonin–norepinephrine reuptake inhibitor (SNRI) with a relatively balanced affinity for the serotonin (SERT) and norepinephrine (NET) transporters, distinguishing it from venlafaxine, which is primarily serotonergic at low doses. Beyond its psychiatric problems, duloxetine is one of the most commonly prescribed agents for chronic pain syndromes — particularly diabetic peripheral neuropathy and fibromyalgia — where its norepinephrine activity in descending inhibitory pain pathways is thought to underlie analgesic efficacy.

| intro = '''Duloxetine''' is a serotonin–norepinephrine reuptake inhibitor (SNRI) with a relatively balanced affinity for the serotonin (SERT) and norepinephrine (NET) transporters, distinguishing it from venlafaxine, which is primarily serotonergic at low doses. Beyond its psychiatric problems, duloxetine is one of the most commonly prescribed agents for chronic pain syndromes, particularly diabetic peripheral neuropathy and fibromyalgia, where its norepinephrine activity in descending inhibitory pain pathways is thought to underlie analgesic efficacy.

| pharmacokinetics = Well-absorbed orally with ~50% bioavailability, though substantial interindividual variability. Extensive first-pass metabolism, primarily via '''CYP1A2''' (major) and CYP2D6 (minor). Highly protein-bound (>90%). Half-life ~12 hours; steady state in ~3 days. No active metabolites of clinical significance. Capsules are enteric-coated — should not be crushed or chewed.

| pharmacokinetics = Well-absorbed orally with ~50% bioavailability, though substantial interindividual variability. Extensive first-pass metabolism, primarily via '''CYP1A2''' (major) and CYP2D6 (minor). Highly protein-bound (>90%). Half-life ~12 hours; steady state in ~3 days. No active metabolites of clinical significance. Capsules are enteric-coated, should not be crushed or chewed.

| pharmacodynamics = Inhibits reuptake of both serotonin and norepinephrine at the synaptic cleft via SERT and NET. The serotonergic and noradrenergic effects are relatively balanced across the clinical dose range (60–120 mg/day), unlike venlafaxine. Modest indirect dopaminergic activity in the prefrontal cortex (via NET inhibition, since DA reuptake in PFC depends partly on NET). Minimal affinity for muscarinic, histaminic, or alpha-adrenergic receptors.

| indications = * Major depressive disorder

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| effects = ''Therapeutic:'' improved mood, reduced anxiety, reduced neuropathic and musculoskeletal pain.

''Common adverse:'' nausea (~25%, usually improves over 1–2 weeks), dry mouth, somnolence, fatigue, constipation, decreased appetite, hyperhidrosis, sexual dysfunction, insomnia.

| adverse = * '''Hepatotoxicity''' — rare but well-documented; avoid in significant alcohol use or chronic liver disease

| adverse = * '''Hepatotoxicity''', rare but well-documented; avoid in significant alcohol use or chronic liver disease

* '''Elevated blood pressure''' — dose-dependent; monitor especially at doses >60 mg

* '''Elevated blood pressure''', dose-dependent; monitor especially at doses >60 mg

* '''Serotonin syndrome''' — especially with concurrent serotonergic agents

* '''Serotonin syndrome''', especially with concurrent serotonergic agents

* '''Suicidality warning''' in patients under 25

* '''Hyponatremia / SIADH''' — especially in elderly

* '''Hyponatremia / SIADH''', especially in elderly

* '''Bleeding risk''' — additive with anticoagulants/NSAIDs

* '''Bleeding risk''', additive with anticoagulants/NSAIDs

* '''Mydriasis / angle-closure glaucoma''' — caution in untreated narrow-angle glaucoma

* '''Mydriasis / angle-closure glaucoma''', caution in untreated narrow-angle glaucoma

* '''Urinary hesitancy'''

* '''Discontinuation syndrome''' — among the more pronounced of the SNRI/SSRI class; dizziness, paresthesias ("brain zaps"), irritability, nausea

* '''Discontinuation syndrome''', among the more pronounced of the SNRI/SSRI class; dizziness, paresthesias ("brain zaps"), irritability, nausea

| interactions = * '''MAOIs''' — serotonin syndrome; contraindicated

| interactions = * '''MAOIs''', serotonin syndrome; contraindicated

* '''CYP1A2 inhibitors''' (ciprofloxacin, fluvoxamine, enoxacin) — substantially increase duloxetine levels; avoid combination

* '''CYP1A2 inhibitors''' (ciprofloxacin, fluvoxamine, enoxacin), substantially increase duloxetine levels; avoid combination

* '''Other serotonergic agents''' — triptans, tramadol, linezolid, lithium, St. John's wort

* '''Other serotonergic agents''', triptans, tramadol, linezolid, lithium, St. John's wort

* '''Anticoagulants / antiplatelets / NSAIDs''' — additive bleeding risk

* '''Anticoagulants / antiplatelets / NSAIDs''', additive bleeding risk

* '''CYP2D6 substrates''' — duloxetine is a moderate CYP2D6 inhibitor; can elevate levels of metoprolol, propafenone, flecainide, certain TCAs

* '''CYP2D6 substrates''', duloxetine is a moderate CYP2D6 inhibitor; can elevate levels of metoprolol, propafenone, flecainide, certain TCAs

| pregnancy_details = Category C. Third-trimester use associated with persistent pulmonary hypertension of the newborn (PPHN) and neonatal adaptation syndrome (jitteriness, feeding difficulty, respiratory distress). Risk-benefit decision; if continuation is needed, sertraline is often preferred among SNRIs/SSRIs in pregnancy. Excreted in breast milk in low amounts.

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* Response and adverse effects at each follow-up

| counseling = * Take with or without food, at the same time each day.

* '''Swallow the capsule whole''' — do not crush or chew (enteric-coated).

* '''Swallow the capsule whole''', do not crush or chew (enteric-coated).

* Full mood effect emerges over 2–4 weeks; pain relief is often faster.

* '''Do not stop abruptly''' — taper gradually to minimize discontinuation symptoms.

* '''Do not stop abruptly''', taper gradually to minimize discontinuation symptoms.

* Avoid heavy alcohol use due to liver toxicity risk.

* Report symptoms of serotonin syndrome (agitation, hyperthermia, tremor, diarrhea) or hepatotoxicity (jaundice, dark urine, upper abdominal pain).

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