Duloxetine vs. Fluoxetine | Similarities, Differences

From time to time, it’s normal to experience a rough patch and feel down on yourself. A bit of depression is a natural human emotion and reminds us that we’re alive. In many cases, going through these challenges helps us grow, and eventually, we’re able to move forward with the lessons we’ve learned and use that hurt to be stronger than before. While that’s the case for some, it’s not applicable to all, and the depression some people experience extends far beyond being natural and can have a major impact on your life. 

Going through a rough patch or mild depression doesn’t typically warrant chemical relief, and doing yoga or exercising can be enough. However, for someone dealing with major depressive disorder, their treating physician could recommend drugs like duloxetine or fluoxetine. As someone battling depression, it’s hard enough to try and figure out which medicine will provide the best relief, and if you’ve discussed this with your doctor, we’re here to shed some clarity on the topic. 

Depression is a common mental disorder, and the World Health Organization estimates that more than 264 million people suffer from it globally. The condition is the leading cause of disability worldwide and is a significant contributor to the overall global burden of disease. Statistics also show that women are more affected than men. In worst-case scenarios, depression can lead someone to have suicidal thoughts, or worse, following through and hurting themselves. Help is of the utmost importance, especially if you’re battling dark thoughts. 

According to the same publication, an estimated 800,000 people die by suicide each year, which is the second leading cause of death in 15 to 29-year-olds. Getting the right treatment for depression is crucial, and if you’re someone battling depression or suicidal thoughts, help is available to you. Depression typically stems from a chemical imbalance in your brain that only chemical relief in the form of antidepressants can manage. 

Duloxetine and fluoxetine are both prescription antidepressants used to treat depressive disorders. However, both work differently in the body. Antidepressants fall into many different categories, but the two most common are selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SSNRIs). Fluoxetine is an SSRI medication, while duloxetine is an SNRI.

If you’re trying to decide which medication is right for you or a loved one, continue reading to see how these two antidepressants work in the body. 


Fluoxetine, also known as Prozac, is a commonly administered antidepressant medication. It’s considered a selective serotonin reuptake inhibitor (SSRI), meaning it works to enhance the effects of serotonin in our brain. The drug is commonly prescribed to treat various mental disorders, including depression and obsessive-compulsive disorder (OCD). However, it can also be used to treat bulimia and panic disorders.

Fluoxetine is taken orally as a capsule, tablet, or as a delayed-release capsule. The medication can also be taken as a solution orally. You can take the medication with or without medication, and if you’ve been prescribed the drug, your doctor will likely start you off on a low dose before increasing it gradually. This is dependent on how it affects you.

The drug, in capsule form, comes in a variety of doses that ranges from 10 milligrams (mg), 20mg, and 40 mg. Doctors advise against using more than 80 mg a day, which is the maximum effective dose. The delayed-release version comes in 90 mg but should only be ingested once a week. 

MedlinePlus mentions that you won’t experience the full benefits of the drug until you’ve been using it consistently for four to five weeks. You should also not stop using the medication, even if you’re feeling well, unless your doctor suggests otherwise. 

Abrupt cessation of antidepressants will cause uncomfortable and unnecessary withdrawal symptoms. If you believe it’s time to stop using the medication, speak with your treating physician. 


Duloxetine, better known as Cymbalta, is prescribed to treat a broad range of conditions that range from major depressive disorder, fibromyalgia, generalized anxiety disorder (GAD), and chronic musculoskeletal pain. The drug was approved in 2004 and works to regulate serotonin and norepinephrine neurotransmitters in our brain. 

Duloxetine is typically taken one or two times a day without eating, and the doses will vary from 20 mg (milligrams) to 120 mg. The prescribing physician will determine which dose is best for you based on several factors. It’s common to start off with a small dose that’s increased over several weeks. 

Duloxetine vs. Fluoxetine

Despite their similarities, there are some considerable differences between the two drugs. One such difference is the category of medications they fall under. For example:

Duloxetine is prescribed for the following conditions:

  • Panic disorder
  • Depression
  • Bulimia (eating disorder)
  • Obsessive-compulsive disorder (OCD)

Fluoxetine is prescribed for the following conditions:

  • Panic attacks
  • Depression
  • Anxiety disorders
  • Neuropathic pain caused by diabetes
  • Fibromyalgia
  • Depressive episodes that are linked with Bipolar I Disorder (Fluoxetine is something used in conjunction with olanzapine [Zyprexa].)

As you might expect, both medications produce side effects. Although they’re typically mild, they can be uncomfortable in some. Please report any side effects to your physician to determine if the benefits outweigh the risks. 

The side effects of duloxetine include the following:

  • Nausea
  • Insomnia
  • Headache
  • Diarrhea
  • Drowsiness and sleepiness
  • Constipation
  • Decreased appetite
  • Dry mouth
  • High blood pressure

Side effects of fluoxetine include the following:

  • Shakiness
  • Dizziness
  • Headache
  • Agitation
  • Insomnia
  • Fatigue
  • Drowsiness and sleepiness
  • Nausea
  • Nervousness
  • Sore throat
  • Decreased libido
  • Flu-like symptoms
  • Indigestion
  • Ejaculation disorder

Is One Drug More Dangerous Than the Other?

Antidepressant drugs are, for the most part, safe and provide countless therapeutic benefits that help a person dealing with depression. However, as you’ll find with any substance, there can be dangers attached that you should know about before taking them. If you’ve been prescribed one of these medications to treat depression or any of the other symptoms we listed above, make sure to ask your doctor questions about the potential dangers and precautions you should take if you plan on taking them. If the medication works but causes severe side effects, you may need to consider something else.


The manufacturers of the drug published a medical guide to keep others informed about the medication. It mentions some potentially dangerous side effects that duloxetine may cause. These include the following:

  • Changes in blood pressure
  • Adverse skin reactions
  • Abnormal bleeding
  • Suicidal thoughts 

If you’re experiencing suicidal thoughts, please reach out for help immediately. You can contact the National Suicide Prevention Lifeline at 1-800-273-8255.

The guide released by Eli Lilly also warns about a condition called serotonin syndrome, which is when an overabundance of serotonin floods the brain and builds up in your body. Serotonin syndrome is considered life-threatening, and you should reach out for immediate medical attention. The symptoms include:

  • Tremors
  • Dizziness
  • Diarrhea
  • Hallucinations
  • Agitation
  • Twitching
  • Coordination problems
  • Racing heartbeat
  • Vomiting
  • High or low blood pressure
  • Sweating and fever
  • Muscle rigidity
  • Seizures
  • Coma (or other mental status changes)


Although fluoxetine is generally safe to use, there are side effects that should be mentioned. For the majority, neither of these drugs will cause issues, which is why they’re FDA-approved. However, you should always be aware of what to expect. Eli Lilly created a medical guide for this medication as well, and one vital piece of information is that it should never be taken with monoamine oxidase inhibitors (MAOIs). 

Some adverse effects to watch out for include the following:

  • Changes or problems with vision
  • Abnormal bleeding
  • Seizures or convulsions
  • Appetite changes
  • Suicidal thoughts in children, teenagers, or young adults (Eli Lilly mentions that these thoughts might occur within the first few months of treatment or when the dose is altered.)

Like duloxetine, fluoxetine can also cause serotonin syndrome, which we mentioned above. When the body is flooded with serotonin, it’s considered an overdose and should be treated as such. 

Which Drug is Right For Me?

That is a question that can only be answered by a medical professional with access to your medical records. You can do as much research as you want online and learn about the effects of the medication and how it can help, but only a trained physician in this field can make the final determination of what you should take. If you’ve been struggling with depression and natural treatment methods have fallen short, it might be time to consider your next step. Don’t wait another day to get the help you need.

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