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What Are the Differences between Fluoxetine and Paroxetine?

By S. Berger
Updated Feb 03, 2024
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Fluoxetine and paroxetine are two medications that are used to treat depression, as well as other mood and anxiety disorders. They are both part of the family of drugs known as selective serotonin reuptake inhibitors (SSRIs.) Both drugs have a similar action in the brain, and exert similar effects. There are important differences between them, however, that lead to differences in how and when they are prescribed.

Some patients with depression show differences in their responses to fluoxetine versus paroxetine. This is due to individual differences in an enzyme in the brain called the polyglycoprotein (Pgp) transporter. Certain people have copies of this protein that cause it to be extremely active, and remove paroxetine from the brain before it can affect an individual. Fluoxetine is not affected by the Pgp transporter, so it can treat depression in individuals with the more active version of this enzyme.

Both fluoxetine and paroxetine prevent the neurotransmitter serotonin from breaking down in the brain. This allows serotonin to exert greater effects on the brain as a result. Slight differences in their actions mean that these drugs can be used to treat slightly different disorders. For example, fluoxetine is typically used to treat bipolar disorder and cataplexy, whereas paroxetine is most often used to treat generalized anxiety disorder and erectile dysfunction. Both drugs are used in the treatment of major depression, bipolar disorder, panic disorder, and obsessive compulsive disorder, however.

The length of time these drugs remain in the body before being broken down represent a key difference between fluoxetine and paroxetine. Paroxetine is broken down after about a day in most people, whereas fluoxetine remains for about one to three days. This difference has functional significance, because when doctors are weaning patients off of an SSRI, they prefer to use one with a longer half-life to minimize withdrawal effects. A person taking paroxetine may be switched to fluoxetine by a doctor as they taper their dose down in order to avoid withdrawal.

Side effects that occur from taking fluoxetine and paroxetine are quite similar. There are some small differences in the incidence rates of individual side effects, however. Patients taking fluoxetine tend to report slightly more incidents of insomnia and loss of appetite, but those taking paroxetine show higher rates of nausea and somnolence, or drowsiness. Studies that have investigated the efficacy and side effect rates show that both of these drugs are well-tolerated by most people, however, and that the side effects do not impact their usefulness.

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Discussion Comments
By anon997188 — On Nov 27, 2016

@anon975488, My cat takes 10mg fluoxetine tablets, and the mfg is Mylan. It is unfortunately more expensive than capsules, as my pharmacist reminds me each time.

In regards to opening the capsule and sprinkling it on food... @anon975530, it's a no go with my cat. He could taste it and refused the food. The same with a tuna flavored suspension made by a compounding veterinary pharmacy.

By anon975530 — On Oct 27, 2014

@anon975488 -- If the fluoxetine capsule comes apart and has powder or the little balls inside, just open the capsule and sprinkle the contents on the cat's food.

If the capsule is solid, take the medication to a compounding pharmacy and get it made into a liquid suspension, or ground into a powder that you can sprinkle on top of the food. There are alternatives if the preferred medication doesn't come in a cat-friendly food.

By anon975488 — On Oct 27, 2014

I'm investigating this for my cat! They prescribed fluoxetine to my cat in a dose that is only available in capsule form. Now I am ready to go to the doctor just to get Paxil, since fluoxetine is no longer available in 10mg. doses according to the manufacturer and the vet! Sorry, but I'm cutting a 10 mg. paxil into quarters and see if the feline can be treated with that.

By anon960186 — On Jul 09, 2014

I started taking fluoxetine a few months ago and I will go as far to say that it is the reason I am still alive (I was about to kill myself). I had not been prescribed it; I just somehow got it.

I stopped it, and my old depressed, bipolar self came back after about a week of stopping. So I have started taking it every other day, and that on a smaller dose (10mg).

This makes me wonder how much we are a result of the billions of simple chemical-electrical processes in our brain.

By fBoyle — On Apr 29, 2013

@MikeMason-- It's much easier to withdraw from fluoxetine because it has a long half-life. It's exactly the opposite with paroxetine.

By stoneMason — On Apr 29, 2013

@donasmrs-- Before I share my experience, I want to mention that medications affect different people differently. It's good to hear about others' experiences with medications. But keep in mind that you might not react the same way to it.

Now that we got that out of the way, I personally think that paroxetine is more effective but it also has more side effects. If you're already experiencing many side effects from fluoxetine, I'm sure you will have the same issues when you're on paroxetine.

Both of these drugs are fairly similar like the article said. They essentially do the same thing in a slightly different way.

Speak to your doctor about your issues with fluoxetine and your intention to switch to something else. He might prescribe a medication that's going to work even better than these two. If you do switch from fluoxetine, make sure to do it slowly because it does cause withdrawal effects.

By donasmrs — On Apr 28, 2013

I've been taking fluoxetine for the past year and I'm not too happy with it. It has reduced my anxiety and depression but I feel like a zombie on it.

It makes me very tired and sleepy. Even though I'm not as sad anymore, I still don't enjoy anything.

Is paroxetine better than fluoxetine? Does it have less side effects? Do you think I should switch?

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