Duloxetine and fluoxetine are both medications that are used to treat major depression and anxiety disorders. Both drugs are prescribed by physicians and used for short and long-term use. While the drugs have similar effects, duloxetine and fluoxetine work in the brain in different ways. Duloxetine is an SNRI (serotonin-norepinephrine reuptake inhibitor), while fluoxetine is an SSRI (selective serotonin reuptake inhibitor). Learn the difference between these two medications and how they work to relieve common mental health disorders.

What Is Duloxetine?

Duloxetine is sold under the brand name Cymbalta for the treatment of major depression, depression, neuropathic pain, and fibromyalgia. As a serotonin-norepinephrine reuptake inhibitor, the drug works by suppressing a function of your nervous system called reuptake. Reuptake removes chemicals in your nervous system to prevent a build-up and to recycle the chemicals. Duloxetine specifically blocks the reuptake of serotonin and norepinephrine, which are two important neurotransmitters. Serotonin is tied to mood, motivation, and feelings of well-being. Norepinephrine is tied to energy levels and preparing your body for the fight or flight response. Blocking reuptake increases the levels of those chemicals in your system.

What Is Fluoxetine?

Fluoxetine is sold under the brand name Prozac in the United States, and it’s prescribed to treat major depressive disorder, obsessive-compulsive disorder, bulimia, and panic disorders. The drug is a selective-serotonin reuptake inhibitor. It also works through the process of blocking reuptake, but it primarily works on serotonin. They are called selective because they don’t affect other neurotransmitters to a significant degree. 

Differences Between Fluoxetine and Duloxetine

Since fluoxetine and duloxetine work in the brain in different ways, there are several differences between them. Since fluoxetine primarily affects serotonin, it’s typically reserved for mood disorders and may treat a wider variety of mood disorders than duloxetine, including bipolar disorder. Duloxetine works on both serotonin and norepinephrine, so it has applications in treating some issues where fluoxetine wouldn’t be helpful. Issues like nerve pain and fibromyalgia may be treated with duloxetine. 

Both drugs have similar side effects profiles, though some symptoms may be more likely on one and not the other. For instance, fluoxetine is related to a risk of sexual dysfunction, while duloxetine can cause sensory disturbances called paresthesias.

Similarities Between Fluoxetine and Duloxetine

Both drugs can cause a phenomenon called serotonin syndrome, which is a collection of symptoms that’s related to drugs that increase serotonin levels in the body. When there’s a build-up of too much serotonin in the body, it can cause symptoms like anxiety, panic, sweating, fever, changes in heart rate, hypothermia, diarrhea, nausea, tremors, muscle rigidity, and seizures. Serotonin syndrome may be more common if you take a high dose of the drug or mix your medication with other substances. If you start to experience these symptoms, speak to a doctor as soon as possible. 

Both drugs come with an increased risk of suicide. Mental health disorders are complicated and often require a period of trial and error to find the right medication and dose. In some cases, medications can worsen or trigger depression and suicidal thoughts. Both duloxetine and fluoxetine can cause an increased risk of suicidal thoughts or actions.

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