Duloxetine: Difference between revisions
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| pregnancy = Category C | | pregnancy = Category C | ||
| legal = Rx-only | | 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 | | 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 | | 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. | | 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 | | indications = * Major depressive disorder | ||
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* Chronic musculoskeletal pain (osteoarthritis, chronic low back pain) | * Chronic musculoskeletal pain (osteoarthritis, chronic low back pain) | ||
* Stress urinary incontinence (approved in Europe; not FDA-approved) | * Stress urinary incontinence (approved in Europe; not FDA-approved) | ||
| dosing = '''Start:''' 30 mg PO daily × 1 week, then increase to 60 mg daily (target dose for most | | dosing = '''Start:''' 30 mg PO daily × 1 week, then increase to 60 mg daily (target dose for most problems). | ||
'''Range:''' 60–120 mg/day. Higher doses (>60 mg) often add modest benefit at the cost of more side effects. | '''Range:''' 60–120 mg/day. Higher doses (>60 mg) often add modest benefit at the cost of more side effects. | ||
'''Renal/hepatic:''' avoid in CrCl <30 mL/min or significant hepatic impairment. | '''Renal/hepatic:''' avoid in CrCl <30 mL/min or significant hepatic impairment. | ||
| Line 29: | Line 29: | ||
| effects = ''Therapeutic:'' improved mood, reduced anxiety, reduced neuropathic and musculoskeletal pain. | | 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. | ''Common adverse:'' nausea (~25%, usually improves over 1–2 weeks), dry mouth, somnolence, fatigue, constipation, decreased appetite, hyperhidrosis, sexual dysfunction, insomnia. | ||
| adverse = * '''Hepatotoxicity''' | | adverse = * '''Hepatotoxicity''', rare but well-documented; avoid in significant alcohol use or chronic liver disease | ||
* '''Elevated blood pressure''' | * '''Elevated blood pressure''', dose-dependent; monitor especially at doses >60 mg | ||
* '''Serotonin syndrome''' | * '''Serotonin syndrome''', especially with concurrent serotonergic agents | ||
* '''Suicidality warning''' in patients under 25 | * '''Suicidality warning''' in patients under 25 | ||
* '''Hyponatremia / SIADH''' | * '''Hyponatremia / SIADH''', especially in elderly | ||
* '''Bleeding risk''' | * '''Bleeding risk''', additive with anticoagulants/NSAIDs | ||
* '''Mydriasis / angle-closure glaucoma''' | * '''Mydriasis / angle-closure glaucoma''', caution in untreated narrow-angle glaucoma | ||
* '''Urinary hesitancy''' | * '''Urinary hesitancy''' | ||
* '''Discontinuation syndrome''' | * '''Discontinuation syndrome''', among the more pronounced of the SNRI/SSRI class; dizziness, paresthesias ("brain zaps"), irritability, nausea | ||
| interactions = * '''MAOIs''' | | interactions = * '''MAOIs''', serotonin syndrome; contraindicated | ||
* '''CYP1A2 inhibitors''' (ciprofloxacin, fluvoxamine, enoxacin) | * '''CYP1A2 inhibitors''' (ciprofloxacin, fluvoxamine, enoxacin), substantially increase duloxetine levels; avoid combination | ||
* '''Other serotonergic agents''' | * '''Other serotonergic agents''', triptans, tramadol, linezolid, lithium, St. John's wort | ||
* '''Anticoagulants / antiplatelets / NSAIDs''' | * '''Anticoagulants / antiplatelets / NSAIDs''', additive bleeding risk | ||
* '''CYP2D6 substrates''' | * '''CYP2D6 substrates''', duloxetine is a moderate CYP2D6 inhibitor; can elevate levels of metoprolol, propafenone, flecainide, certain TCAs | ||
<pharmaInteractions/> | |||
| 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. | | 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. | ||
| monitoring = * Blood pressure at initiation and dose changes | | monitoring = * Blood pressure at initiation and dose changes | ||
| Line 50: | Line 51: | ||
* Response and adverse effects at each follow-up | * Response and adverse effects at each follow-up | ||
| counseling = * Take with or without food, at the same time each day. | | counseling = * Take with or without food, at the same time each day. | ||
* '''Swallow the capsule whole''' | * '''Swallow the capsule whole''', do not crush or chew (enteric-coated). | ||
* Full mood effect emerges over 2–4 weeks; pain relief is often faster. | * Full mood effect emerges over 2–4 weeks; pain relief is often faster. | ||
* '''Do not stop abruptly''' | * '''Do not stop abruptly''', taper gradually to minimize discontinuation symptoms. | ||
* Avoid heavy alcohol use due to liver toxicity risk. | * 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). | * Report symptoms of serotonin syndrome (agitation, hyperthermia, tremor, diarrhea) or hepatotoxicity (jaundice, dark urine, upper abdominal pain). | ||
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| references = | | references = | ||
}} | }} | ||
[[Category:Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs)]] | |||
[[Category:Antidepressants]] | |||
Latest revision as of 03:16, 19 May 2026
SNRI, Antidepressant, Anxiolytic
Duloxetine
Cymbalta, Drizalma Sprinkle, Irenka, Yentreve
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.
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.
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.
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.
Venlafaxine, Desvenlafaxine, Levomilnacipran, Milnacipran, Fluoxetine, Sertraline
Experience
No personal reports yet
No clinical reports yet
Log in to add your own experience.
Problems
- Major depressive disorder
- Generalized anxiety disorder
- Diabetic peripheral neuropathic pain
- Fibromyalgia
- Chronic musculoskeletal pain (osteoarthritis, chronic low back pain)
- Stress urinary incontinence (approved in Europe; not FDA-approved)
Titration strategies
Start: 30 mg PO daily × 1 week, then increase to 60 mg daily (target dose for most problems). Range: 60–120 mg/day. Higher doses (>60 mg) often add modest benefit at the cost of more side effects. Renal/hepatic: avoid in CrCl <30 mL/min or significant hepatic impairment. Discontinuation: taper gradually over ≥2 weeks; abrupt cessation produces notable discontinuation syndrome.
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.
- 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
- Serotonin syndrome, especially with concurrent serotonergic agents
- Suicidality warning in patients under 25
- Hyponatremia / SIADH, especially in elderly
- Bleeding risk, additive with anticoagulants/NSAIDs
- 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
Pharmacokinetics
Pharmacodynamics
Interactions
- MAOIs, serotonin syndrome; contraindicated
- CYP1A2 inhibitors (ciprofloxacin, fluvoxamine, enoxacin), substantially increase duloxetine levels; avoid combination
- Other serotonergic agents, triptans, tramadol, linezolid, lithium, St. John's wort
- Anticoagulants / antiplatelets / NSAIDs, additive bleeding risk
- CYP2D6 substrates, duloxetine is a moderate CYP2D6 inhibitor; can elevate levels of metoprolol, propafenone, flecainide, certain TCAs
Fluoxetine via Category:Antidepressants exp n/a/5 outcome n/a (n=1) exp 1.0/5 outcome +33.0 (n=1)
How much experience do you have with this combination (1 a little, 5 a lot)?
How did it go? (-100 worst, +100 best)
- checking this mechanism here
Pregnancy and lactation
Monitoring
- Blood pressure at initiation and dose changes
- LFTs at baseline and if symptoms develop; avoid in heavy alcohol use
- Mood and suicidality, particularly first 4 weeks
- Sodium in elderly patients
- Response and adverse effects at each follow-up
Patient counseling
- Take with or without food, at the same time each day.
- 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.
- 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).
Relevant anecdote
No anecdotes yet. Share a relevant one.
Relevant Literature
No literature entries yet.
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See also
Summary
Classes
SNRI, Antidepressant, Anxiolytic
Common uses
Depression, anxiety, neuropathic pain, fibromyalgia, chronic musculoskeletal pain
Pharmacy
Pharmacology
Routes
Oral
Onset
Mood: 2–4 weeks. Pain: often within 1–2 weeks.
Duration
Chronic daily dosing
Half-life
~12 hours
Bioavailability
~50% (highly variable)
Pregnancy
Category C
Legal status
Rx-only
Purported mechanism
Serotonin–norepinephrine reuptake inhibition (balanced)