What Is Duloxetine and How Does It Work?

Duloxetine is a type of antidepressant known as a serotoninnorepinephrine reuptake inhibitor used to treat depression and anxiety. In addition, duloxetine is used to help relieve nerve pain (peripheral neuropathy) in people with diabetes or ongoing pain due to medical conditions such as arthritis, chronic back pain, or fibromyalgia (a condition that causes widespread pain).

Duloxetine may improve your mood, sleep, appetite, and energy level, and decrease nervousness. It can also decrease pain due to certain medical conditions. Duloxetine is known as a serotonin-norepinephrine reuptake inhibitor (SNRI). This medication works by helping to restore the balance of certain natural substances (serotonin and norepinephrine) in the brain.

  • Duloxetine is available under the following different brand and other names: Cymbalta.

What Are Dosages of Duloxetine?

Dosages of Duloxetine

Adult and Pediatric Dosage Forms & Strengths

Capsule, delayed-release

  • 20mg
  • 30mg
  • 40mg
  • 60mg
Dosage Considerations -- Should Be Given As Follows: Major Depressive Disorder
  • 40-60 mg/day taken orally initially (in single daily dose or divided once every 12 hours for 1 week if the patient needs to adjust to therapy)
  • Titrate dose in increments of 30 mg/day over 1 week as tolerated
  • Target dosage: 60 mg/day taken orally (in single daily dose or divided once every 12 hours); not to exceed 120 mg/day (safety of dosages greater than120 mg/day has not been evaluated)
Diabetic Peripheral Neuropathic Pain
  • 60 mg/day taken orally initially (in single daily dose or divided once every 12 hours); consider lowering dosage if tolerability is a concern
  • Target dosage: 60 mg/day taken orally; not to exceed 60 mg/day
Generalized Anxiety Disorder
  • 60 mg/day taken orally initially (in single daily dose or divided once every 12 hours); may be increased in increments of 30 mg/day if tolerability is a concern
  • Target dosage: 60 mg/day taken orally; not to exceed 120 mg/day
  • 30 mg/day taken orally initially for 1 week to allow for therapy adjustment
  • Target dosage: 60 mg/day taken orally; not to exceed 60 mg/day; no additional benefit shown by doses greater than 60 mg in clinical trials
Chronic Musculoskeletal Pain
  • Treatment of chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain
  • 30 mg/day taken orally initially for 1 week to allow for therapy adjustment
  • Target dosage: 60 mg/day taken orally; not to exceed 60 mg/day
Dosing Modifications
  • Severe renal impairment (CrCl greater than 30 mL/min) or end-stage renal disease (ESRD): Use not recommended
  • Hepatic impairment: Use not recommended, because of risk of hepatic injury
  • Dosages 60 mg/day or more have not been shown to offer additional benefits
  • Major depressive disorder and generalized anxiety disorder: Acute episodes often necessitate several months of sustained therapy
  • Diabetic peripheral neuropathic pain: Efficacy for greater than12 weeks has not been studied; if diabetes is complicated by renal disease, consider lower starting dosage with a gradual increase to effective dosage
  • Fibromyalgia: Efficacy for 12 weeks or more has not been studied; continue treatment on basis of individual patient response
  • Chronic musculoskeletal pain: Efficacy for 13 weeks or more has not been studied
  • Uncontrolled narrow-angle glaucoma: Use not recommended due to increased risk of mydriasis


  • Gradually reduce dosage
  • Abrupt discontinuance may result in symptoms (e.g., dizziness, nausea, headache, paresthesia, fatigue, vomiting, irritability, insomnia, diarrhea, anxiety, hyperhidrosis)
  • Wait 14 days or more after discontinuance of monoamine oxidase inhibitor (MAOI) therapy to initiate duloxetine therapy; wait 5 days or more after discontinuance of duloxetine therapy to initiate MAOI therapy
Generalized Anxiety Disorder
  • Less than 7 years: Safety and efficacy not established
  • 7-17 years: 30 mg taken orally once daily initially; after 2 weeks, may consider increasing dose to 60 mg/day
  • Recommended dosage range: 30-60 mg/day
  • Some patients may benefit from doses greater than 60 mg/day; if increased beyond 60 mg/day, use increments of 30 mg/day
  • The maximum dose studied was 120 mg/day; safety of doses greater than 120 mg/day has not been evaluated
renal impairment
  • Avoid use in patients with severe renal impairment (GFR <30 mL/min)
Hepatic Impairment Administration
  • Because of enteric coating, must be swallowed whole; do not chew, crush, or open capsule and sprinkle contents in food or liquid
  • Can be taken without regard to meals

What Are Side Effects Associated with Using Duloxetine?

Side effects associated with the use of duloxetine include:

  • Nausea
  • Dry mouth
  • Headache
  • Drowsiness
  • Fatigue

Less common side effects of duloxetine include:

  • Constipation
  • Dizziness
  • Insomnia
  • Diarrhea
  • Loss of appetite
  • Abdominal pain
  • Increased sweating
  • Agitation
  • Runny or stuffy nose
  • Vomiting
  • Male sexual dysfunction
  • Decreased sex drive
  • Musculoskeletal pain
  • Upper respiratory tract infection (URTI)

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

What Other Drugs Interact with Duloxetine?

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

  • Severe interactions of duloxetine include:
  • Duloxetine has serious interactions with at least 86 different drugs.
  • Duloxetine has moderate interactions with at least 128 different drugs.
  • Duloxetine has mild interactions with at least 45 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

What Are Warnings and Precautions for Duloxetine?


  • 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 greater than 24 years.
  • There was a reduction in risk with antidepressant use in patients 65 years or older.
  • In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for the emergence of suicidal thoughts and behaviors.
  • Advise families and caregivers of the need for close observation and communication with the prescriber.
  • This medication contains duloxetine. Do not take Cymbalta if you are allergic to duloxetine or any ingredients contained in this drug.
  • Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.


Concomitant use of duloxetine with MAOIs intended to treat psychiatric disorders.

Co-administration with serotonergic drugs

  • Wait at least 14 days between discontinuance of MAOI and initiation of duloxetine; wait at least 5 days between discontinuance of duloxetine and initiation of MAOI
  • Starting duloxetine inpatient being treated with linezolid or IV methylene blue is contraindicated because of increased risk of serotonin syndrome
  • If linezolid or IV methylene blue must be administered, discontinue duloxetine immediately and monitor for central nervous system (CNS) toxicity; duloxetine may be resumed 24 hours after the last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first

Effects of Drug Abuse

  • There are no effects of drug abuse for duloxetine.

Short-Term Effects

  • This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Avoid alcoholic beverages.
  • If you have diabetes, duloxetine may affect your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

Long-Term Effects

  • There are no long-term effects of drug abuse for duloxetine.


  • CYP1A2 inhibitors or thioridazine should not be co-administered
  • Use caution in severe renal impairment, ESRD
  • Heavy alcohol use
  • Suicidality; monitor for clinical worsening and suicide risk, especially in children, adolescents, and young adults (18-24 years) during early phases of treatment and alterations in dosage
  • Serotonin syndrome or neuroleptic malignant syndrome-like reactions may occur; discontinue and initiate supportive therapy; closely monitor patients concomitantly receiving triptans, antipsychotics, and serotonin precursors
  • Neonates exposed to serotonin-norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding
  • Screen patients for bipolar disorder; risk of mixed/manic episodes is increased in patients treated with antidepressants
  • May cause activation of mania or hypomania
  • Increased risk of hepatotoxicity, sometimes fatal; monitor for abdominal pain, hepatomegaly, elevations in hepatic transaminases exceeding 20 times upper limit of normal; jaundice; cholestatic jaundice with minimal elevations of hepatic transaminases have also been reported; use not recommended in patients with substantial alcohol use or chronic liver disease
  • SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymosis, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs are known to affect platelet function may add to this risk
  • Severe skin reactions (e.g., erythema multiforme and Stevens-Johnson syndrome); discontinue at the first appearance of blisters, peeling rash, mucosal erosions, or any other sign of hypersensitivity if no other etiology can be identified
  • Orthostatic hypotension and syncope, especially during week 1 of therapy; monitor patients taking drugs that increase risk of orthostatic hypotension; consider dose reduction or discontinue therapy in patients who experience symptomatic orthostatic hypotension, falls, and/or syncope
  • Hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH); cases of serum sodium less than 110 mmol/L have been reported to be reversible upon discontinuance
  • Diabetes due to worsening of glycemic control in some patients; monitor increases in fasting blood glucose and hemoglobin A1c
  • Monitor weight and growth in adolescents and children; decrease in appetite and weight loss reported
  • Urinary hesitation and retention
  • Cognitive or motor function impairment; use with caution when operating heavy machinery
  • Bone fractures reported with antidepressant treatment; consider the possibility of bone fracture if the patient complains of unexplained bone pain or joint tenderness or experiences bruising or swelling
  • May cause or exacerbate sexual dysfunction
  • Use caution in gastroparesis, hypertension, controlled narrow-angle glaucoma, renal impairment, or seizure disorders
  • May lower seizure threshold when administered concurrently with other drugs that lower seizure threshold
  • Use caution when administering concomitantly with CNS depressants
  • Risk of mydriasis; may trigger angle closure attack in patients with angle-closure glaucoma with anatomically narrow angles without a patent iridectomy
  • Headache, dizziness, nausea, diarrhea, paresthesia, vomiting, irritability, insomnia, hyperhidrosis, anxiety, and fatigue were reported in patients following abrupt discontinuation of duloxetine
  • Therapy may increase blood pressure; measure blood before initiating treatment and periodically throughout treatment
  • Abnormal bleeding reported when used in combination with aspirin, NSAIDs, or other drugs that affect coagulation
  • Angle-closure glaucoma reported in patients with untreated anatomically narrow angles that do not have a patent iridectomy and are being treated with antidepressants
  • Use with caution in patients with conditions that slow gastric emptying

Pregnancy and Lactation

  • During pregnancy, use duloxetine with caution if the benefits outweigh the risks. Animal studies show risk and human studies not available or neither animal nor human studies done. Neonates exposed to serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine or selective serotonin reuptake inhibitors (SSRIs) late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding.
  • Duloxetine enters breast milk. Using duloxetine is not recommended during lactation unless the benefits greatly outweigh the risks.
Medscape. Duloxetine.

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