Educational only — not medical advice. If you’re in crisis or thinking about suicide: call or text 988 (U.S.) or your local emergency number. Support resources. Under construction and review—see the updates log.

duloxetine

Adjunctive therapy

Brand: Cymbalta

Published 2025-09-28 · Last reviewed 2025-10-05 · 4 references

Content sourced from FDA labeling (DailyMed) and peer-reviewed literature.

Print sheet Review evidence

At a glance

Class: Adjunctive therapy·Typical dose: Major depressive disorder (clinical depression) and generalized anxiety disorder: typical initiation is 30 mg once daily for one week for tolerability, then 60 mg once daily. If needed, 90–120 mg/day is sometimes used (divide when >60 mg/day), though antidepressant benefit often plateaus beyond 60 mg/day.·Half-life: Single-dose mean 12 h; Single-dose range 8–17 h; Steady-state mean 12 h·LAI available: No

Class: Adjunctive therapy
Typical dose: Major depressive disorder (clinical depression) and generalized anxiety disorder: typical initiation is 30 mg once daily for one week for tolerability, then 60 mg once daily. If needed, 90–120 mg/day is sometimes used (divide when >60 mg/day), though antidepressant benefit often plateaus beyond 60 mg/day.
Half-life: Single-dose mean 12 h; Single-dose range 8–17 h; Steady-state mean 12 h
LAI available: No

Quick answers

What is duloxetine?: Duloxetine (Cymbalta®) is a serotonin-norepinephrine reuptake inhibitor approved for major depressive disorder, generalized anxiety disorder, diabetic neuropathic pain, fibromyalgia, and chronic musculoskeletal pain.
What is Cymbalta?: Cymbalta is a brand name for duloxetine.
What is Cymbalta (duloxetine) used for?: Label indications include: Major depressive disorder; generalized anxiety disorder; diabetic peripheral neuropathic pain; fibromyalgia; chronic musculoskeletal pain.
What drug class is Cymbalta (duloxetine)?: SNRI Antidepressant.
What is the mechanism of action of Cymbalta (duloxetine)?: Serotonin-norepinephrine reuptake inhibitor (SNRI).
What strengths does Cymbalta (duloxetine) come in?: Delayed-release capsules: 20 mg, 30 mg, 40 mg, 60 mg.
What is the maximum recommended dose of Cymbalta (duloxetine)?: Maximum recommended dose: 120 mg/day.
What is the maximum dose of Cymbalta (duloxetine) for major depressive disorder (clinical depression)?: Major depressive disorder (clinical depression) and generalized anxiety disorder: typical initiation is 30 mg once daily for one week for tolerability, then 60 mg once daily. If needed, 90–120 mg/day is sometimes used (divide when >60 mg/day), though antidepressant benefit often plateaus beyond 60 mg/day.
What is duloxetine hydrochloride (HCl)?: Duloxetine hydrochloride (duloxetine HCl) is the active ingredient in Cymbalta® and generic delayed-release capsule formulations.

General information

Duloxetine (Cymbalta®) is a serotonin-norepinephrine reuptake inhibitor approved for major depressive disorder, generalized anxiety disorder, diabetic neuropathic pain, fibromyalgia, and chronic musculoskeletal pain.

Duloxetine hydrochloride (duloxetine HCl) is the active ingredient in Cymbalta® and generic delayed-release capsule formulations.

It is often preferred when depressive or anxiety symptoms coexist with neuropathic or somatic pain. Enteric-coated capsules (20, 30, 40, 60 mg) permit once-daily dosing; higher doses can be divided for tolerability.

The compare view and duloxetine evidence feed can support discussions of analgesic benefits, blood-pressure considerations, and augmentation plans; mania-prevention planning can be coordinated via the bipolar disorder hub.

U.S. approvals

Major depressive disorder (2004)
Generalized anxiety disorder (2007)

Formulations & strengths

Delayed-release capsules: 20 mg, 30 mg, 40 mg, 60 mg.

Generic availability

Generic delayed-release capsules available since 2013.

Moderate CYP2D6 inhibition makes interaction checks important (TCAs, antipsychotics, tamoxifen). Because of hepatotoxicity risk, it is generally avoided in substantial hepatic impairment or chronic heavy alcohol use. Coordination with the bipolar disorder hub can support mania-prevention planning in bipolar-spectrum disorders.

View labelExact

Mechanism of action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Inhibits serotonin (SERT) and norepinephrine (NET) transporters with a ~10:1 affinity ratio; norepinephrine reuptake becomes clinically significant at ≥60 mg/day.

Minimal direct antagonism at muscarinic, histamine, or adrenergic receptors; weak dopamine reuptake inhibition is clinically negligible.

SERT and NET inhibitor with minimal off-target receptor binding.

Metabolism & pharmacokinetics

Enteric-coated pellets dissolve in the intestine; Tmax ~6 hours; elimination half-life ~12 hours (steady state in ~3 days).
Extensively metabolized in the liver via CYP1A2 and CYP2D6 to inactive metabolites, eliminated in urine (~70%) and feces (~20%).
Exposure increases in moderate hepatic impairment and severe renal impairment (CrCl <30 mL/min); both are relative contraindications.

Dosing & administration

Major depressive disorder (clinical depression) and generalized anxiety disorder: typical initiation is 30 mg once daily for one week for tolerability, then 60 mg once daily. If needed, 90–120 mg/day is sometimes used (divide when >60 mg/day), though antidepressant benefit often plateaus beyond 60 mg/day.
Maximum recommended dose: 120 mg/day.
Generally avoided in severe renal impairment (CrCl <30 mL/min) and in substantial hepatic impairment or heavy alcohol use.
Discontinuation symptoms can occur with abrupt stopping; gradual tapering over ≥2 weeks is common.

Monitoring & labs

Blood pressure and heart rate at baseline and periodically, especially during titration and at higher doses.
Liver-injury symptoms (jaundice, dark urine, abdominal pain, pruritus), particularly in patients with alcohol use disorder or hepatic disease; LFTs are obtained when clinically indicated.
Sodium in older adults or diuretic users if symptoms suggest hyponatremia (confusion, fatigue, falls).
Medication reconciliation for serotonergic combinations and for CYP2D6 substrates (TCAs, antipsychotics, beta-blockers, tamoxifen).

Duloxetine is often chosen for combined mood and pain symptoms; track both (functioning and pain interference) to guide dose decisions.

Adverse effects

FDA boxed warnings

Boxed warning: Antidepressants increase suicidality risk in children, adolescents, and young adults; closer monitoring is common during initiation and dose changes.

Common side effects (≥10%)

Nausea: Most common; usually transient.
Dry mouth/constipation: Hydration, fiber, and sugar-free lozenges can help.
Somnolence or insomnia: Dose timing is often adjusted to mitigate.
Hyperhidrosis: Hydration can become a practical issue; symptoms may worsen in warm climates.
Sexual dysfunction: Decreased libido and delayed orgasm.

Other notable effects

Dose-related increases in blood pressure and heart rate—baseline and periodic monitoring are common, especially during titration.
Rare hepatotoxicity—baseline LFTs are sometimes obtained in higher-risk patients, and symptoms (pruritus, dark urine, jaundice) warrant clinical evaluation.
Hyponatremia/SIADH, especially in older adults or diuretic use.
Urinary hesitation, orthostatic dizziness, and weight change are reported.

Interactions

Contraindicated with MAOIs, linezolid, or IV methylene blue because of serotonin syndrome; appropriate washouts are required.
CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) markedly increase duloxetine exposure—combinations are generally avoided or alternatives selected.
Duloxetine is a moderate CYP2D6 inhibitor—dose adjustments and clinical monitoring may be needed for TCAs, antipsychotics, beta-blockers, and tamoxifen.
Serotonergic agents (SSRIs, SNRIs, triptans, tramadol, St. John’s wort) increase serotonin syndrome risk; counseling often covers symptom recognition and when to seek care.
Additive bleeding risk with NSAIDs, antiplatelets, and anticoagulants; gastroprotection is sometimes considered.

Other useful information

Counseling often covers signs of liver injury and when to seek care for sustained hypertension, jaundice, or abdominal pain.
Weight, blood pressure, and (when relevant) glycemic control are commonly tracked over time.
Smoking (CYP1A2 induction) may modestly decrease levels; clinical impact varies.

References

Related hubs:SMI toolkit·Support resources