duloxetine

Adjunctive therapy

Brands: Cymbalta

Last reviewed 2025-10-05

Reviewed by PsychMed Editorial Team.

View details

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)?
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.

Snapshot

Class: Adjunctive therapy
Common US brands: Cymbalta
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2025-10-05

Label indications

Major depressive disorder; generalized anxiety disorder; diabetic peripheral neuropathic pain; fibromyalgia; chronic musculoskeletal pain.

View labelExact

Clinical Highlights

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.
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.
The compare view and duloxetine evidence feed can support discussions of analgesic data, blood-pressure considerations, and augmentation strategies; mania-prevention planning can be coordinated via the bipolar disorder hub when bipolar-spectrum risk is present.
Major depressive disorder (FDA 2004)
Generalized anxiety disorder (FDA 2007)
Generic: Generic delayed-release capsules available since 2013.

Dosing & Formulations

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

Boxed warning: Antidepressants increase suicidality risk in children, adolescents, and young adults; closer monitoring is common during initiation and dose changes. 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: Sweating can be bothersome; hydration can become a practical issue, especially in warm climates.
Sexual dysfunction: Decreased libido and delayed orgasm.

Drug 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.

Practice Notes

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.

Coordination with mood-stabiliser teams and the bipolar disorder hub can support mania/hypomania risk mitigation in bipolar spectrum disorders.
Smoking (CYP1A2 induction) may modestly decrease levels; clinical impact varies.

References

Cymbalta (duloxetine) prescribing information — DailyMed (2025)
APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)
Duloxetine for chronic pain and depression: an evidence review — Pain Medicine (2022)
Wernicke2008 Duloxetine Hepatic