Duloxetine (Cymbalta, Drizalma Sprinkle)

This article provides a comprehensive overview of duloxetine, including its indications, precautions, side effects, interactions, and other important treatment information.

Key Takeaways:

• Duloxetine is an antidepressant in the SNRI class of medications. It is used not only for depression, but also anxiety, chronic pain, and other conditions.
• Duloxetine has many possible side effects, some of which are severe and life-threatening. Severe side effects include serotonin syndrome, worsening depression, and liver dysfunction, among several others.
• Duloxetine has potentially harmful interactions with many drugs and medications. Precautions are also set in place for pregnant and nursing women, children, and individuals with various mental or physical conditions.

Duloxetine Overview

Duloxetine is an antidepressant that belongs to the serotonin and norepinephrine reuptake inhibitor (SNRI) class of medications. It was first patented in the United States in 1990, and officially came to market in 2004. It is only available as a prescription. ^[1]

Due to its effects on serotonin, norepinephrine, and other neurotransmitters, duloxetine is used for several different concerns, such as depression, anxiety, and pain. It has several official uses and several off-label uses, all of which are described below.

Brand Names

In the United States, duloxetine is available under the following brand names: ^[2]

• Cymbalta®
• Drizalma Sprinkle®
• Irenka®

Cymbalta® was the original brand name for duloxetine, and is the most common overall.

How Does Duloxetine Work?

Duloxetine primarily works by inhibiting the uptake of two neurotransmitters, serotonin and norepinephrine (also called noradrenaline), which leads to an increase in their effects in the brain and nervous system. In turn, increased levels of serotonin and norepinephrine may help with mood, depression, anxiety, pain signaling, and other effects. ^{[1] [3]}

Duloxetine also indirectly increases dopamine levels, which may provide additional benefits for mood and mental well-being. ^[1]

When is it prescribed?

There are several established duloxetine uses. Duloxetine is officially approved for the treatment of the following conditions: ^[1]

• Major depressive disorder (MDD)
• In adults
• Generalized anxiety disorder (GAD)
• In adults and children aged 7 and older
• Fibromyalgia
• In adults and children aged 13 and older
• Diabetic peripheral neuropathy
• In adults
• Chronic musculoskeletal pain, such as back pain or osteoarthritis
• In adults

In addition, duloxetine is sometimes prescribed off-label for the following conditions: ^[1]

• Chemotherapy-induced peripheral neuropathy
• Stress urinary incontinence

What to Know Before Taking Duloxetine

There are several important things to know before taking duloxetine. Understanding this information is critical for safe, effective, and appropriate treatment.

Duloxetine may interact with many medications, including potentially dangerous interactions with monoamine oxidase inhibitors (MAOIs). If you stop taking duloxetine, you need to wait at least 5 days before taking an MAOI. ^[2]

A more detailed list of possible drug interactions is in the section below titled “Drug Interactions with Duloxetine”.

Duloxetine may cause your mental health to change in unexpected ways, including an increase in depression and suicidal thoughts. This risk is highest in children and young adults under the age of 24, particularly when you start taking duloxetine or when the dosage is changed. Contact your doctor or healthcare provider right away if you notice new or worsening depression, suicidal thoughts or behaviors, rapid mood swings, or other symptoms indicative of suicidality. ^{[2] [4]}

Some individuals are at a greater risk of side effects and complications when taking duloxetine. In particular it’s important to tell your doctor if you have any of the following conditions or symptoms: ^{[2] [5] [6]}

• Low sodium levels in blood
• Glaucoma
• Recent heart attack
• High blood pressure
• Other heart problems
• Seizures
• Bleeding problems
• Any stomach problems
• Heart, liver, or kidney disease
• Diabetes
• Depression, bipolar disorder, or another mental disorder

Make sure to tell your doctor if you drink or have ever drunk alcohol, used street drugs, or overused prescription medications.

Dosage

Duloxetine comes in capsule form and is administered orally. Listed below are the recommended dosages of duloxetine for its approved indications: ^{[1] [7]}

• GAD: 30 to 60 mg, once per day
• MDD: 40 to 60 mg per day, in one or two divided doses.
• May start with 30 mg in sensitive individuals
• Fibromyalgia: Typically 30 to 60 mg once per day
• May start lower at 20 mg in sensitive individuals
• Diabetic peripheral neuropathy: Generally 60 mg, once per day
• Chronic musculoskeletal pain: 30 to 60 mg, once per day

Precautions

Duloxetine should not be used in individuals with significant liver or kidney problems. ^[3]

Duloxetine is generally not recommended for use by pregnant or breastfeeding women, due to the risk of birth defects, pregnancy complications, and other side effects. Duloxetine may be used in these situations only if the benefits significantly outweigh the risks. ^{[2] [4]}

You may not be able to take duloxetine, or you may require a modified dose, if you have any of the conditions or symptoms mentioned in the previous section. Always tell your doctor your full detailed health history, and make sure to have any necessary tests or evaluations performed, to make sure duloxetine is safe for you.

Side Effects

There are many possible side effects of duloxetine. Some side effects diminish or go away with continued use, while other duloxetine side effects may not get better over time. Contact your doctor or healthcare provider right away if you notice any side effects or unusual reactions after taking duloxetine, especially when you first start taking it or when the dosage is changed.

Common Side Effects

The most common side effects of duloxetine are: ^{[3] [4]}

• Nausea
• Dry mouth
• Sleepiness
• Fatigue
• Constipation
• Decreased appetite
• Increased sweating

Other relatively common duloxetine side effects include: ^{[1] [2] [5] [6]}

• Headache
• Nervousness
• Restlessness
• Trouble sleeping
• Diarrhea
• Increased urination
• Night sweats
• Stomach pain
• Vomiting
• Flushing
• Weight changes
• Muscle pain or cramps
• Tremors
• Decreased libido
• Sexual dysfunction:
• In men: delayed ejaculation, erectile dysfunction
• In women: delayed orgasm or inability to orgasm

This list does not contain all possible side effects.

Rare and Severe Side Effects

There are also several rare side effects of duloxetine, some of which can be serious or even life-threatening. The following serious side effects should be reported to your doctor immediately: ^{[1] [2] [4] [5] [6]}

• Liver dysfunction, which includes the following signs and symptoms:
• Yellowing of the skin or eyes
• Dark-colored urine
• Pain in the upper right area of the stomach
• Itching
• Abnormal bruising or bleeding
• Orthostatic hypotension (drop in blood pressure when standing)
• Suicidal thoughts or behaviors
• Severe allergic reactions (anaphylaxis), which include the following symptoms:
• Swelling of the eyes, mouth, tongue, face, throat, or other body parts
• Trouble breathing or swallowing
• Sudden dizziness, drowsiness, or confusion
• Skin, tongue, or lips turn blue, gray or pale
• Mania or hypomania, which includes symptoms such as:
• Euphoria
• Severe restlessness
• Excessive energy
• Inflated self-esteem
• Increased reckless or dangerous behaviors
• Decreased need for sleep
• Increased blood pressure
• Seizures
• Hyponatremia (low sodium levels in blood)

Duloxetine also increases the risk of serotonin syndrome, especially at higher dosages and when it is combined with other drugs that increase serotonin. There are several symptoms of serotonin syndrome, including agitation, confusion, rapid heart rate, dilated pupils, severe muscle stiffness or twitching, vomiting, and loss of coordination. Severe cases can lead to coma, seizures, or death. ^{[4] [5]}

Drug Interactions with Duloxetine

There are many possible duloxetine interactions. Taking duloxetine with other drugs that increase serotonin increases the risk of serotonin syndrome. This may occur when duloxetine is combined with the following drugs or substances: ^{[2] [5]}

• MAOIs (e.g. methylene blue, isocarboxazid, linezolid, phenelzine)
• Selective-serotonin reuptake inhibitors (SSRIs) (e.g. fluvoxamine, paroxetine)
• Other SNRIs (e.g. desvenlafaxine, venlafaxine)
• St. John’s wort
• Tryptophan
• Other antidepressants
• Opioids (e.g. tramadol)
• Triptans (e.g. sumatriptan)
• Amphetamines

Duloxetine may also interact with other drugs and medications, such as: ^{[2] [4] [5] [6]}

• NSAIDs (e.g. ibuprofen, aspirin, naproxen)
• Benzodiazepines (e.g. lorazepam, temazepam)
• Certain antibiotics (e.g. linezolid)
• Vesicular monoamine transporter 2 inhibitors (e.g. valbenazine, tetrabenazine)
• Antipsychotics (e.g. iloperidone, clozapine)
• Selective norepinephrine reuptake inhibitors (e.g. atomoxetine)
• Alcohol

This list does not contain all possible drug interactions. Consult your doctor and tell them everything you currently take or have taken, including prescription and over-the-counter medications, vitamins, herbs, and dietary supplements.

Cessation and Withdrawal

Stopping duloxetine can cause uncomfortable symptoms. These are much more likely to occur if you suddenly stop taking duloxetine without your doctor’s approval. You may experience the following withdrawal symptoms when stopping duloxetine: ^{[2] [4]}

• Dizziness
• Nausea
• Headache
• Fatigue
• Insomnia
• Irritability
• Diarrhea
• Increased sweating
• Anxiety
• Pain, burning, numbness, or tingling in hands or feet
• Nightmares

To help minimize or avoid these symptoms, your doctor will lower the dose of duloxetine that you take in a gradual, controlled manner. ^[4]

When to Stop Taking Duloxetine

You should only stop taking duloxetine after talking with your doctor and receiving their approval and direction to do so. Some individuals may be able to stop duloxetine once their symptoms have improved significantly and are unlikely to return.

For individuals with depression or anxiety, most doctors recommend taking the medication for at least several months. In many cases, treatment lasts at least 6 months after you start to feel better. ^[7]

Some individuals with chronic anxiety, depression, or pain may need to take duloxetine long-term or indefinitely.

Duloxetine FAQs

Listed below are frequently asked questions about the use of duloxetine.

Can you take duloxetine while pregnant?

It is generally not recommended to take duloxetine if you’re pregnant, especially during the third trimester. Your doctor will only prescribe duloxetine if the benefits strongly outweigh the risks.

Does duloxetine cause weight gain?

Yes, duloxetine may cause weight gain in some individuals. However, it is not a very common side effect.

How long does duloxetine take to work?

Duloxetine typically starts to work within 1 to 4 weeks. Individual responses will vary.

Author

Jack Cincotta

Jack Cincotta holds a M.S. degree in Psychology. He is also a board-certified holistic health practitioner through AADP and an AFPA-certified holistic health coach and nutritionist.

Activity History - Last updated: March 19, 2026, Published date: March 19, 2026

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Reviewer

David MilesPharmD

David is a seasoned Pharmacist, natural medicines expert, medical reviewer, and pastor.

Activity History - Medically reviewed on April 5, 2026 and last checked on March 19, 2026