What are the indications, dosing, and potential side effects of Duloxetine (Cymbalta)?

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Last updated: June 18, 2025View editorial policy

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From the Guidelines

Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor (SNRI) that should be used at a dose of 60 mg once daily, with potential increases to 120 mg daily, for the treatment of diabetic peripheral neuropathic pain, as it has been shown to improve neuropathy-related quality of life and reduce pain perception, as evidenced by studies such as 1. The medication is primarily indicated for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain. Some key points to consider when prescribing duloxetine include:

  • The typical starting dose is 30 mg once daily for one week before increasing to 60 mg once daily, which is the usual maintenance dose.
  • Dosage adjustments are necessary for patients with renal impairment.
  • Common side effects include nausea, dry mouth, constipation, decreased appetite, fatigue, somnolence, increased sweating, and dizziness.
  • More serious potential adverse effects include increased suicidal thoughts (particularly in young adults and adolescents), serotonin syndrome, hepatotoxicity, abnormal bleeding, severe skin reactions, and discontinuation syndrome if stopped abruptly.
  • Duloxetine works by inhibiting the reuptake of serotonin and norepinephrine in the central nervous system, increasing the availability of these neurotransmitters and thereby improving mood, reducing anxiety, and decreasing pain perception, as described in 1 and 1.
  • The medication should be taken at the same time each day, swallowed whole without crushing or chewing, and should not be discontinued without gradual tapering under medical supervision to avoid withdrawal symptoms. It's also important to note that duloxetine may interact with other medications, such as those metabolized by CYP1A2 and CYP2D6, and concomitant administration with MAOIs is contraindicated due to increased risk of serotonin syndrome, as highlighted in 1.

From the FDA Drug Label

Duloxetine delayed-release capsules may be taken with or without food. If you miss a dose of duloxetine delayed-release capsules, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of duloxetine delayed-release capsules at the same time The most common side effects of duloxetine delayed-release capsules include: nausea dry mouth sleepiness fatigue constipation loss of appetite increased sweating dizziness

The indications of Duloxetine are not explicitly stated in the provided drug labels. The dosing instructions for Duloxetine are to take the capsules exactly as the healthcare provider tells you to, swallowing them whole without chewing or crushing. The potential side effects of Duloxetine include:

  • Liver damage
  • Changes in blood pressure and falls
  • Serotonin Syndrome
  • Abnormal bleeding
  • Severe skin reactions
  • Discontinuation symptoms
  • Manic episodes
  • Visual problems
  • Seizures or convulsions
  • Low salt (sodium) levels in the blood
  • Nausea
  • Dry mouth
  • Sleepiness
  • Fatigue
  • Constipation
  • Loss of appetite
  • Increased sweating
  • Dizziness 2

From the Research

Indications for Duloxetine

  • Duloxetine is licensed for the treatment of major depressive disorders, urinary stress incontinence, and the management of neuropathic pain associated with diabetic peripheral neuropathy 3, 4.
  • It is also effective in treating painful diabetic peripheral neuropathy, fibromyalgia, and painful physical symptoms in depression 3, 4.
  • Additionally, duloxetine is FDA approved for the treatment of generalized anxiety disorder (GAD) in doses of 30 mg to 120 mg daily 5.
  • It has been shown to be effective in the treatment of major depressive disorder (MDD), with significant improvements in core emotional symptoms and painful physical symptoms associated with depression 6.

Dosing of Duloxetine

  • The recommended dosage of duloxetine is 60 mg daily, which has been shown to be effective in treating painful diabetic peripheral neuropathy, fibromyalgia, and painful physical symptoms in depression 3, 4.
  • For the treatment of GAD, duloxetine can be started at 30 mg daily and titrated up to 60 mg daily after one week 7.
  • For MDD, duloxetine can be administered at dosages ranging from 40 to 120 mg/day, with significant improvements seen at the highest recommended dosage of 60 mg once daily 6.

Potential Side Effects of Duloxetine

  • Common adverse events associated with duloxetine include nausea, constipation, dry mouth, and insomnia, which are generally mild and transient 7, 5.
  • Duloxetine has a dose-dependent effect on adverse events, with more common side effects at higher doses 3, 4.
  • Serious adverse events are rare, but 16% of participants stopped the drug due to adverse effects in some studies 3, 4.
  • Duloxetine should not be used in combination with CYP 1A2 inhibitors or nonselective, irreversible monoamine oxidase inhibitors due to potential drug interactions 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia.

The Cochrane database of systematic reviews, 2014

Research

Duloxetine for treating painful neuropathy or chronic pain.

The Cochrane database of systematic reviews, 2009

Research

Duloxetine in the treatment of generalized anxiety disorder.

International journal of general medicine, 2009

Research

[Duloxetine for chronic pain management: pharmacology and clinical use].

Masui. The Japanese journal of anesthesiology, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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