Living with lupus sometimes means dealing with symptoms that can appear suddenly — like fatigue (extreme tiredness that doesn’t improve with rest). It’s not always easy to know if a new symptom is caused by the condition, a treatment, or something else entirely. This is the case for some people who take duloxetine (Cymbalta).

“What’s been your experience with Cymbalta?” one MyLupusTeam member asked. “I have extreme fatigue.”

Fatigue is a known side effect of duloxetine, and many people living with lupus are already familiar with it. Read on to learn how duloxetine may contribute to fatigue and what steps you can take to manage it.

What Is Duloxetine?

Duloxetine is an antidepressant in a class of medications called serotonin-norepinephrine reuptake inhibitors (SNRIs). It works by increasing levels of serotonin and norepinephrine, brain chemicals that help regulate mood and manage pain.

The U.S. Food and Drug Administration (FDA) first approved duloxetine to treat symptoms of major depressive disorder. It’s now also used for generalized anxiety disorder and certain types of chronic (long-term) pain — such as fibromyalgia and musculoskeletal pain, which may also occur in people with lupus.

Like all medications, duloxetine can cause side effects. In addition to fatigue, common side effects include:

• Diarrhea
• Heartburn
• Abdominal (stomach) pain
• Constipation
• Loss of appetite
• Dry mouth
• Weight changes

What Does Fatigue From Duloxetine Look Like?

Many people who take duloxetine report feeling tired or low on energy, but this side effect doesn’t affect everyone the same way. For some, fatigue improves with time.

One member of MyLupusTeam shared, “I took my first dose of Cymbalta yesterday and was extremely tired last night and today. After 8.5 hours of sleep last night, I feel like I haven’t slept in days. I’m dizzy from being so exhausted.”

A year later, they posted an update explaining how they managed to overcome the fatigue. “The first thing I did was start taking it in the evening. … The fatigue let up after about eight to 12 weeks. It has helped with some of the chronic aches I have in my chest and helps pretty significantly with depression.”

How Does Duloxetine Cause Fatigue?

Duloxetine affects how the brain manages chemicals like serotonin and norepinephrine, which help regulate mood, energy, and alertness. In some people, this can lead to fatigue — especially early on or when adjusting the dose.

Serotonin and norepinephrine normally help you feel awake and focused. But when these chemicals are increased too much, it may disrupt the brain’s balance, contributing to drowsiness or low energy.

Duloxetine can also interfere with sleep in some people. It may make it harder to fall asleep or stay asleep, leading to poor sleep quality. This, in turn, can cause daytime fatigue and drowsiness.

It’s important to remember that everyone reacts differently to medications. Some people may be more sensitive to fatigue as a side effect of duloxetine, depending on their body chemistry or other health conditions.

Also, fatigue is a common symptom of the conditions duloxetine is used to treat, like depression and chronic pain. People living with lupus often report feeling tired, experiencing brain fog, and having trouble sleeping. Many also live with fibromyalgia, a condition that causes widespread pain and fatigue that can result in tiredness.

“I’ve been on it for years, and I think it helps me,” said a MyLupusTeam member about duloxetine. “I was tired before it, and I’m tired now. So I never thought it was the Cymbalta, just lupus!”

How Can You Manage Duloxetine’s Side Effects?

If you experience fatigue while taking duloxetine, it’s important to talk with your healthcare provider. They can assess your overall health, help determine whether the fatigue is related to the medication, and adjust your treatment plan if needed.

Depending on your situation, your provider may also recommend lifestyle changes to help reduce fatigue, such as:

• Improving your sleep habits — Going to bed and waking up at the same time each day can help your body get into a rhythm.
• Staying physically active — Gentle movement like walking, stretching, or yoga can boost energy levels over time.
• Managing stress — Mindfulness, breathing exercises, or talking to a therapist may help reduce emotional and physical fatigue.

Additionally, they may adjust the dosage or explore alternative medications if fatigue continues and significantly affects your quality of life. Oftentimes, fatigue can be improved by simply taking the medication in the evening or at bedtime.

You shouldn’t discontinue or modify your medication regimen without proper medical guidance. Abruptly stopping duloxetine can lead to withdrawal symptoms and other potential complications.

A MyLupusTeam member shared, “Cymbalta was horrible for me. I was very tired, but please don’t just stop it like I did. The withdrawal was horrible. Maybe give it a few days and see if the fatigue goes away. If not, speak to your doctor.”

Your healthcare provider can give you individualized medical advice on safe discontinuation or switching medications if needed to avoid serious side effects. They may suggest an alternative medication, such as a selective serotonin reuptake inhibitor (SSRI).

Living with lupus can be challenging, especially when new symptoms show up unexpectedly. It’s not always clear whether they’re caused by the condition itself, a medication, or something else entirely. Checking in regularly with your healthcare providers and keeping track of any changes can help you better understand and manage life with lupus.

Join the Conversation

On MyLupusTeam, people share their experiences with lupus, get advice, and find support from others who understand.

Did you experience tiredness, sleepiness, or other adverse effects while taking duloxetine? Let others know in the comments below.