How long does duloxetine stay in your system?

In this article:

• How long does duloxetine stay in your system?
• What affects the duration?
• Side effects & risks
• How long do the side effects last?
• Discontinuation
• Alternatives

In this article

• How long does duloxetine stay in your system?
• What affects the duration?
• Side effects & risks
• How long do the side effects last?
• Discontinuation
• Alternatives

Duloxetine is an antidepressant medication used to treat mental health conditions like major depressive disorder (MDD) in adults and generalized anxiety disorder (GAD) in adults and children older than seven. Sold under the brand name Cymbalta, this prescription drug is also FDA approved for treating fibromyalgia, diabetic peripheral neuropathic pain (DPNP), and chronic musculoskeletal pain.

Cymbalta belongs to a class of medications called serotonin-norepinephrine reuptake inhibitors (SNRIs). These medications work by increasing the levels of neurotransmitters serotonin and noradrenaline—mood-enhancing chemicals—in the brain. While duloxetine begins working in the body within hours, most people notice improvements in symptoms such as mood or anxiety after 1 to 2 weeks, with full therapeutic benefits often taking 6 to 8 weeks to develop. The medication is designed to provide continuous, long-acting relief of mental health symptoms. Each dose of duloxetine can stay in your body for up to two days or more before elimination. If you and your provider decide to stop the medication due to side effects or to switch to a different treatment, here’s what you need to know about how long it sticks around. 

How long does duloxetine stay in your system?

“For most people, duloxetine stays in the body for approximately 2.5 to 3 days, which is about five half-lives,” says Erika Gray, Pharm.D., Founder & Chief Medical Officer at ToolBox Genomics. The medication should be completely eliminated from the body after about five days. While it is primarily eliminated through urine, about 20% is processed out of your system through feces. 

The peak performance time of duloxetine is between 6 and 18 hours, and at the 18-hour mark, most people still have about 50% of the drug in their body. “Because the medication has an enteric coating on the capsule, it is not absorbed immediately, and absorption typically starts a couple of hours after the medication reaches the stomach,” explains Dr. Gray.

Currently, there aren’t any tests to check for duloxetine in someone’s body, and therapeutic drug monitoring is not done. In rare cases, a specialized toxicology panel can show whether the drug is present in your system or not.

Factors that influence how long duloxetine stays in your system

If you decide to stop taking duloxetine under the guidance of a healthcare provider, certain factors may influence how long duloxetine stays in your system.

Liver health

The liver plays an important role in metabolizing many medications, including duloxetine. Your liver health can influence the length of time this medication stays in your body. 

For example, if your liver enzymes are elevated, which usually happens when the liver is not working efficiently, the half-life of duloxetine could increase from approximately 12 hours to over 45 hours, Dr. Gray explains. This increased half-life can increase the risk of side effects, as each dose remains in your body longer, increasing the amount of medication in your system at any time.

Medication dose

Dosage significantly affects the absorption, distribution, metabolism, and excretion of duloxetine. The range of possible doses of Cymbalta goes from 20 mg to 120 mg. Increasing the dose of this medication typically reduces the efficiency of its elimination, leading to its increased concentration in the blood, which can increase the risk of side effects.  

Genetics

Your body metabolizes duloxetine using liver enzymes called cytochrome P450, specifically CYP2D6 and CYP1A2. Genetically, some people are “poor metabolizers,” meaning their bodies process the medication more slowly than usual. This can make the medication build up in your system and increase side effects.

Age

How the body absorbs, distributes, metabolizes, and excretes duloxetine changes with age. As you get older, the rate at which this medication clears from your body may decrease. 

Clinical trials suggest a 1% reduction in clearance with each year between ages 25 and 75. However, other factors play significant roles, and it is not necessary to adjust the dosage based on age alone.  

Smoking

It helps to avoid smoking when taking medications like duloxetine. According to Dr. Gray, smoking makes your body process duloxetine more quickly and can decrease the concentration, which means you may not receive as many of the benefits of that particular dose. 

Quitting smoking is often not easy, but tips like finding healthy distractions, self-care, trying something different, and finding safe substitutes to cigarettes may help. You can also consider joining support groups, medications, and using helpful tools online.

Side effects and risks of duloxetine

“Duloxetine is generally safe, very widely prescribed, and has a strong track record of use in psychiatry, neurology, and primary care,” says Sharon Batista, MD, an Assistant Clinical Professor of Psychiatry at Mount Sinai Hospital. But, this medication may be associated with adverse effects like:

• Nausea and vomiting
• Headache
• Fatigue and drowsiness
• Constipation
• Reduced appetite and weight loss
• Abdominal pain
• Diarrhea
• Dry mouth
• Sexual problems like erectile dysfunction and decreased libido

Serious side effects of Cymbalta may include:

• Confusion
• Tendency for suicidal thoughts
• Severe changes in mood
• Hallucinations
• Seizures
• Increased bleeding
• Difficulty breathing or swallowing
• Acute angle-closure glaucoma
• Cataracts
• Hepatotoxicity (liver damage due to exposure to a harmful substance)
• Serotonin syndrome (a life-threatening buildup of high serotonin in the body)
  

While these serious side effects can sound alarming, they are rare, especially when the medication is used appropriately and with regular monitoring, Dr. Batista says.

Some drug interactions might also impact the safety or efficacy of duloxetine. According to Dr. Batista, some common interactions include: 

• Non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and anticoagulants: They can increase bleeding risk when combined.
• Serotonergic drugs (e.g., SSRIs, SNRIs, tramadol, lithium, and St. John’s wort): They increase the risk of serotonin syndrome.
• Alcohol: It raises the risk of liver injury. It is best to avoid it when you are on duloxetine medication. 
• CYP1A2 and CYP2D6 inhibitors (e.g., fluvoxamine, fluoxetine, and cimetidine): They can increase duloxetine levels in the system, leading to toxicity.
• Monoamine oxidase inhibitors (MAOIs) also pose major drug interaction concerns. MAOIs include medications like Nardil (phenelzine) and Zyvox (linezolid), prescribed to treat depression. When combined with duloxetine, they can cause serotonin syndrome.
  

This is not a complete list. To help ensure there are no drug interactions and reduce the risk of side effects, Ritu Goel, MD, a board-certified psychiatrist practicing in California, advises that the safest approach is to keep an up-to-date medication and supplement list and review the list with your prescriber or pharmacist regularly, especially when starting or stopping any new medications or supplements.

“For people on daily duloxetine, I often check blood pressure and liver function, and ask about changes in mood, sleep, or appetite. If they are on blood thinners, migraine medications, or other antidepressants, I look out for signs of serotonin syndrome, increased bleeding risk, or excessive sedation,” Dr. Goel adds. 

How long does it take for side effects to go away after stopping duloxetine?

After stopping duloxetine, “most side effects resolve within days to weeks,” says Dr. Batista. Factors like how long you have been taking it and the dosage can influence how long it takes for side effects to go away.

Furthermore, certain side effects—especially the severe ones—may need some form of treatment to help them resolve. For instance, one case report of serotonin syndrome caused by duloxetine in an older woman showed that symptoms and signs associated with the syndrome disappeared within two days after treatment with hydration and diazepam.

Dr. Batista further explains that duloxetine is an SNRI. SNRIs are associated with more frequent and severe withdrawal symptoms than selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants that acts by primarily increasing only serotonin levels in the brain. Cymbalta withdrawal symptoms you may experience may include “brain zaps, dizziness, sweating, and irritability.” These may last 2 to 4 weeks or longer, depending on the patient. Withdrawal symptoms can also occur if a dose is missed, not just when stopping completely, which is why it is important to take duloxetine consistently and taper gradually under medical supervision.

Tapering schedule and discontinuation

Drug tapering means gradually reducing the dosage of a drug to reduce the risk of withdrawal effects. Dr. Goel says the safest way to discontinue duloxetine is a slow taper over weeks or months, with adjustments along the way. 

“A typical plan involves reducing the dose by 30% to 50% every 1 to 2 weeks, adjusted to symptom severity,” Dr. Batista adds. She suggests addressing specific symptoms with supportive care to help manage withdrawal symptoms. “In some cases, I’ve found that short-term use of medications (e.g., anti-nausea, sleep aids, or anxiolytics) can help manage withdrawal.”

Dr. Goel also suggests that getting enough rest, staying hydrated, gentle movement, and avoiding alcohol may help manage withdrawal. “During withdrawal, I usually advise against high-intensity workouts or anything that can significantly raise the heart rate if you experience dizziness, light-headedness, or unsteadiness,” she says.

Activities that involve quick reflexes, like contact sports or heavy weightlifting, might be risky until symptoms improve. Most light to moderate activities, such as stretching, walking, and gentle yoga, are typically okay. 

Duloxetine alternatives

If duloxetine doesn’t work well for you or you have too many side effects, your healthcare provider may suggest alternatives to duloxetine. According to Dr. Goel, the options include:

• Other SNRIs, such as Effexor (venlafaxine) or Savella (milnacipran)
• SSRIs, like Prozac (fluoxetine) or Celexa (citalopram)
• Bupropion
• Mirtazapine
• Nerve-pain medicines like gabapentin or Lyrica (pregabalin)

Non-medication approaches, such as therapy or lifestyle changes, may also improve symptoms. The alternative recommendation will often depend on the condition and symptoms being treated or why duloxetine was prescribed in the first place. 

For instance, to treat mood and anxiety, Dr. Goel suggests that cognitive-behavioral therapy (CBT), mindfulness-based stress reduction, regular aerobic exercise, adequate sleep hygiene, and balanced nutrition can be effective. For treatment-resistant depression, prescription options like esketamine (administered under medical supervision) may be considered. 

Alternatively, nutraceuticals such as ashwagandha, magnesium L-threonate, and omega-3 fatty acids can help in selected cases. Dr. Goel adds that vitamin D (if deficient), an anti-inflammatory diet pattern, and gentle movement practices like tai chi or qigong can support general well-being and complement both mood and pain management.