Last reviewed · How we verify
Cymbalta (duloxetine)
Potentiates serotonergic and noradrenergic activity in the CNS through unknown exact mechanisms.
Duloxetine is an SNRI indicated for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain across adult and select pediatric populations. The drug demonstrates moderate to significant strength with a 12-hour half-life and extensive hepatic metabolism via CYP1A2 and CYP2D6, requiring careful management of drug interactions. Key risks include serotonin syndrome with MAOIs, increased bleeding with anticoagulants and NSAIDs, and substantial drug interactions with CYP inhibitors. Duloxetine remains a widely used therapeutic option with established efficacy across multiple pain and psychiatric conditions when appropriate drug interaction monitoring is maintained.
At a glance
| Generic name | duloxetine |
|---|---|
| Also known as | Cymbalta, Irenka |
| Sponsor | Eli Lilly and Company |
| Drug class | Serotonin and norepinephrine reuptake inhibitor (SNRI) |
| Target | Serotonin and norepinephrine reuptake |
| Modality | Small molecule |
| Therapeutic area | Metabolic |
| Phase | FDA-approved |
| First approval | 2004-08-03 (United States) |
Mechanism of action
Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS. Duloxetine functions as an SNRI, affecting neurotransmitter levels through inhibition of reuptake mechanisms. The drug's therapeutic effects across multiple indications (depression, anxiety, pain) are attributed to this dual serotonergic and noradrenergic activity.
Approved indications
- Chronic Musculoskeletal Pain
- Diabetic peripheral neuropathy
- Female stress incontinence
- Fibromyalgia
- Generalized anxiety disorder
- Major depressive disorder
Boxed warnings
- WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older [see Warnings and Precautions (5.1) ] . In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber [see Warnings and Precautions (5.1) ] . WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants ( 5.1 ) Monitor for worsening and emergence of suicidal thoughts and behaviors ( 5.1 )
Common side effects
- Back pain
- Constipation
- Diarrhea
- Nausea
- Fatigue
- Irritability
- Headache
- Insomnia
- Somnolence
- Dizziness
Drug interactions
- Fluvoxamine (CYP1A2 inhibitor)
- Paroxetine (CYP2D6 inhibitor)
- Fluoxetine (CYP2D6 inhibitor)
- Quinidine (CYP2D6 inhibitor)
- Cimetidine (CYP1A2 inhibitor)
- Quinolone antimicrobials (ciprofloxacin, enoxacin) (CYP1A2 inhibitors)
- NSAIDs, Aspirin, Warfarin
Key clinical trials
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled Switch Study to Evaluate the Safety, Tolerability and Efficacy of Milnacipran in Patients With an Inadequate Response to Duloxetine for the (Phase 4)
- A Pilot Study Assessing Duloxetine's Efficacy in Atypical Depression (Phase 4)
- Intravenous Infusion of Esketamine in Combination With Pregabalin and Duloxetine for Postherpetic Neuralgia (NA)
- Investigation of the Effect of Initial Central Sensitization Severity on Treatment Response in Patients With Fibromyalgia (N/A)
- Methadone to Treat Painful Chemotherapy Induced Peripheral Neuropathy (METACIN): a Randomized Double-blind Controlled Trial (Phase 2)
- Incorporating Drug Metabolism by the Human Gut Microbiome Into Personalized Medicine (Phase 1)
- The Role of SNRI's in the Prophylaxis of Depression in the First Year Following Lower Extremity Fragility Fractures in Geriatric Patients (Phase 4)
- Leveraging EEG for Antidepressant Prediction With Duloxetine and Bupropion (LEAP-DB): A Multicenter, Randomized, Blinded Outcome Study of EEG-guided Treatment With Duloxetine Versus Bupropion in Adult (Phase 4)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| FDA label | Mechanism, indications, dosing, boxed warnings, drug interactions |
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- Cymbalta CI brief — competitive landscape report
- Cymbalta updates RSS · CI watch RSS
- Eli Lilly and Company portfolio CI