What to Know About Duloxetine Side Effects

Duloxetine — sold as Cymbalta, Drizalma Sprinkle, and Irenka — is one of the most commonly prescribed medications in the United States. It's used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and diabetic peripheral neuropathy.

Like all medications, Duloxetine can cause side effects. Most are mild and go away within a few weeks as your body adjusts. But some are serious and require immediate medical attention. This guide covers what to expect, who's most at risk, and when to call your doctor.

What Is Duloxetine?

Duloxetine is a Serotonin-Norepinephrine Reuptake Inhibitor (SNRI). It works by increasing levels of serotonin and norepinephrine in your brain — two chemicals that help regulate mood and pain. If you want a deeper look at how it works, read our guide on Duloxetine's mechanism of action explained in plain English.

Common Side Effects

The following side effects are reported most frequently in clinical trials. They usually appear within the first one to two weeks and often improve as your body adjusts:

• Nausea — The most commonly reported side effect. Taking Duloxetine with food can help reduce it.
• Dry mouth — Sipping water and chewing sugar-free gum can provide relief.
• Drowsiness or fatigue — You may feel sleepy, especially when first starting. Avoid driving until you know how it affects you.
• Constipation — Increasing fiber and water intake can help.
• Decreased appetite — Some people lose their appetite, which may lead to weight loss early on.
• Dizziness — Stand up slowly from sitting or lying positions to reduce dizziness.
• Increased sweating — Hyperhidrosis (excessive sweating) is a known SNRI side effect.
• Insomnia — Some people have trouble sleeping. Taking Duloxetine in the morning may help.

These side effects are usually not dangerous, but if any persist for more than two to three weeks or become bothersome, talk to your doctor. They may adjust your dose or suggest ways to manage them.

Serious Side Effects

The following side effects are less common but can be serious or life-threatening. Contact your doctor immediately or go to the emergency room if you experience any of these:

Suicidal Thoughts or Behavior

Duloxetine carries an FDA boxed warning about increased risk of suicidal thinking and behavior in children, adolescents, and young adults under 25 — particularly during the first few months of treatment or after dose changes. If you or someone you know experiences worsening depression, new or worsening anxiety, agitation, panic attacks, or thoughts of self-harm, seek help immediately. Call 988 (Suicide & Crisis Lifeline) or go to your nearest emergency room.

Serotonin Syndrome

This rare but potentially fatal condition occurs when serotonin levels become dangerously high. Symptoms include agitation, hallucinations, rapid heartbeat, fever, muscle stiffness, and loss of coordination. Risk increases when Duloxetine is taken with other serotonergic medications.

Liver Damage (Hepatotoxicity)

Duloxetine can cause liver injury. Signs include dark urine, yellowing of the skin or eyes (jaundice), unexplained nausea, upper right abdominal pain, or unusual fatigue. People who drink alcohol heavily or have pre-existing liver disease are at higher risk.

Severe Skin Reactions

Rarely, Duloxetine can cause serious skin reactions including blistering, peeling, or widespread rash. Stop taking the medication and seek medical attention if this occurs.

Increased Bleeding Risk

Duloxetine affects serotonin, which plays a role in blood clotting. Taking it with blood thinners, NSAIDs (like Ibuprofen), or Aspirin may increase your risk of bruising or bleeding.

Low Sodium (Hyponatremia)

Older adults are most at risk. Symptoms include headache, difficulty concentrating, memory problems, confusion, weakness, and unsteadiness — which can lead to falls.

Severe Blood Pressure Elevation

Duloxetine may raise blood pressure in some people. Your doctor may monitor your blood pressure during treatment.

Angle-Closure Glaucoma

Duloxetine can trigger an acute attack of angle-closure glaucoma in people with untreated narrow angles. Symptoms include eye pain, vision changes, and swelling or redness around the eye.

Discontinuation Syndrome

Stopping Duloxetine abruptly can cause dizziness, nausea, headache, irritability, insomnia, "brain zaps" (electric shock-like sensations), and flu-like symptoms. Never stop Duloxetine suddenly. Always taper gradually under your doctor's guidance.

Specific Populations at Higher Risk

Certain groups should use extra caution with Duloxetine:

• Young adults under 25 — Higher risk of suicidal thoughts, especially early in treatment.
• Older adults — Greater risk of falls, low sodium, and bleeding.
• People with liver disease — Duloxetine is processed by the liver and should be avoided in severe hepatic impairment.
• People with kidney disease — Avoid if creatinine clearance is less than 30 mL/min.
• Pregnant women — Third-trimester use may cause complications in newborns. Discuss risks and benefits with your OB/GYN.
• Breastfeeding women — Duloxetine passes into breast milk. Not generally recommended while nursing.

How to Manage Common Side Effects

Here are practical tips for the most frequent side effects:

• Nausea: Take with food. Start at a lower dose (20 mg) and increase gradually.
• Dry mouth: Stay hydrated. Sugar-free lozenges or gum can stimulate saliva.
• Drowsiness: Take the dose at bedtime if your doctor agrees.
• Insomnia: Take it in the morning. Practice good sleep hygiene.
• Constipation: Eat high-fiber foods, drink plenty of water, and stay physically active.
• Dizziness: Get up slowly. Avoid sudden position changes.
• Sweating: Wear breathable fabrics. Use clinical-strength antiperspirant.

If side effects don't improve after a few weeks, your doctor may lower your dose or consider switching to an alternative. Learn about alternatives to Duloxetine if needed.

Final Thoughts

Most people tolerate Duloxetine well, and many side effects fade within the first few weeks. The key is to communicate openly with your doctor — especially if you notice anything unusual or if side effects are affecting your quality of life.

If you're just getting started with Duloxetine, learn more about what Duloxetine is, its uses, and dosage. And if cost is a concern, check out our guide to saving money on Duloxetine.

Need to fill your prescription? Use Medfinder to find a pharmacy with Duloxetine in stock near you.