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Zoloft vs Prozac: Side Effects, Benefits

a bottle of pills; prozac analyzed in relation to zoloft


Zoloft vs Prozac

Everyone’s heard of these two drugs.  They’re that popular.  But what are they?  How do they compare?  And in the analysis of Zoloft vs Prozac, which comes on top?

Zoloft might have a slight advantage over Prozac.  Yet they both can have serious side effects, and don’t always work.

For a discussion about the pros and cons of antidepressants, you may be interested in reading a balanced approach to antidepressants.

Let’s start at the beginning.


Zoloft was discovered during the 70s/80s by accident.  A team at Pfizer was researching compounds for a condition not related to depression.  One of those, what would later become Zoloft, had impressive selective serotonin reuptake inhibitor (SSRI) effects.  Against the wishes of higher management, the team pushed for the development of the medication.

Initial approval of Zoloft almost didn’t happen.  The FDA was concerned about the poor efficacy of the medication, and by the improper design of the studies.  Zoloft didn’t seem to work well, and the studies that showed that were not examples of good science.  Yet they gave it the green light.

Within 15 years, it would become the most popular antidepressant, with 29 million prescriptions in 2007.


Prozac was one of the first SSRI medications altogether.  It was discovered slightly before Zoloft.

It’s entry to the market changed how depression is treated.  The earlier medications, the MAO inhibitors and Tricyclics, had very significant and serious side effects.  It seemed at first that Prozac was much safer.  And it worked about as well.

In 2007, 22 million prescriptions were filled for fluoxetine, the generic form of Prozac.

Comparison of Prozac vs Zoloft

Both work in about the same time span, of 4-6 weeks.  Both should be taken once daily, and the difference in doses aren’t important.  Both have some benefit in 50-70% of those who take them.

Crucially, they are both SSRIs, and they both work by almost the same mechanism.  This means that they aren’t really that different (and this is also true for many other antidepressants like Paxil).

Some analysis of many, many patients showed slight superiority in Zoloft’s efficacy for treating depression.  One paper put it the difference between the two that Prozac is certainly not better than and probably not worse than Zoloft.

The main difference between the two may be in side effects.  One study analyzing Zoloft vs Prozac found that Prozac had slightly less “retardation,” or feeling of being slowed down.  The same study, however, showed that Prozac might have more anxiety and irritability.

On the other hand, diarrhea is more associated with Zoloft than Prozac.

They both have similar rates of sexual dysfunction, and similar rates of physical addiction.  And they both tend to cause significant weight gain.


Antidepressants are very hit and miss.  They often don’t work, and it’s possible that a lot of their effect is from placebo.  They are powerful medications and have been shown to double the risk of suicidal thinking in some analysis.  Because they have significant side effects, a high percentage of people taking them stop shortly after starting.

That said, they can also be life-changing.  For some people, they can make normal living possible.  As always, the key is to balance the potential benefits against the potential harms of a treatment.

Related Articles:

  1. Why am I Depressed?
  2. Weight Gain from Zoloft and Prozac
  3. 10 Ideas to Treat Resistant Depression
  4. The Top 5 Depression Songs
  5. Ethical Issues in Health & Medicine

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This post was written by on Wednesday, September 16, 2009. This author has written 223 posts on this blog and has 6329497 total posts views.

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  1. Your opinion is biased and uneducated. If you want to give people better information, stick to facts only and don’t make sweeping untrue blanket statements.

    I came here for info and am leaving in disgust.

  2. Dear Tanya,

    Thank you for reading and sharing your reaction. If you would be so kind, I’d love to hear more about what you think are untrue/inaccurate, so I can fix the problem.

    Best wishes,

  3. Perhaps if you would state where you got your information from or what type of studies, by who, and where were preformed to obtain this information then you would sound more educated. To me, even if your facts are true or not, it sounds very opinionated.

  4. Same opinion as Tania and Rei… it seems as if you want to discredit antidepressants so then what’s left?

  5. Zoloft actually does “normalize” most people who had a severe head injury. I am not irritable and anxious anymore. It’s nice to feel calm and normal like everyone else. It does depend on each individual. If you are upset with your findings here, then go to the doctor. They are the professionals.

  6. I agree that there isn’t a lot of factual information here — heavy on opinion. This is subjective opinion rather than objective facts. Maybe stating that up front would be best. Probably, the author is ideologically against SSRIs. Those who’ve had success with them, may equally be simply “for them” because of their positive experience.

    There’s still a lot unknown about why SSRIs work and what happens to the body systems as a result of using them, especially in combination with other medications, supplements, diets, genetics, etc.

    Medication and exercise are very helpful and natural, but I’ve read of people who despite years of meditation could not shake their depression without the help of an SSRI. One is not morally superior to the other. It is important to know the truth and be open to relieving suffering without judging one another.

    May all be happy and free of suffering.

  7. Excuse the misspelling. I meant: “MediTation and exercise are very helpful…”

  8. Hello everyone! I have been diagnosed for GAD 18 years ago. Back then I’d have 3 to 4 panic attacks a day! I have suffered a lot. I still strugle with depression every once in a while and I have tried most of the anti-depressants out there. I must say that I mostly agree with this article and suggest that anyone interested in a more profound information I suggest you go to each drug’s websites and other medical sources. I believe the article above is opinionated yes, but not unbiased. I completely agree that some SSRi’s can do more harm than good to some people, myself being one of those people. I have for the last 5 years been treating with holistic treatments (acupuncture, massage therapy, yoga, exercise and lots of salmon!). You’re welcome to visit my webiste for more information about me. In the meantime I wish everyone much luck in finding the right treatment for you. Much peace, hapinness and light to all…

  9. I’ve taken Prozac (varying dosage of 20 -40mg/daily) for about 18 yrs.
    I recently lost my 4 yr old son and feel more anxious and depressed than I have in a long time – this is my 2nd child to lose, my 5 yr old daughter passed away almost 9 yrs ago.
    When I see my doc I’m tossing around the idea of switching from Prozac to Zoloft – thoughts on this – will I notice a change?
    thank you for your time

    • I was on Prozac for about 4 years 40 milligrams a day and I had anger issues that were still unresolved and when I was switched to zoloft first at 50 milligrams and then up to 100 milligrams a day which I have been at for 2 years I do not have nearly nearly the anger issues I used to. However you need to be careful as I was off of Zoloft for two weeks and had a suicide attempt but now that I’m back on it everything seems ok…

      • I should add that I take Remeron 30 milligrams a night in addition to help me sleep but I never take Zoloft at night with the Remeron because it gives me horrible dreams

  10. I couldnt help but shed tears to what you wrote cs. I can’t imagine what your gont through but lose my mind. I just don’t understand. You have really put my kids in perspective. Also, zoloft will benefit you. Guaranteed. Those Anxious depressed feelings will tarnish over time. God bless you and your family. I pray for your strength. 

  11. zoloft since 2001

    RE: Zoloft vs Prozac: Side Effects, Benefits (posted on September 16, 2009)

    Thank you for your analysis. I don’t know where you got your info or experience but I have recently been prescribed Prozac. I’ve been reluctant to take it b/c I’ve been on and off Zoloft for 10 years. Every other online research I’ve done has left me to conclude that they are identical. The two things you mention that should make Prozac better for me is:

    1. I never like the “too happy and retard” feeling Zoloft gave me
    2. The diarrhea b/c I have an ileostomy

    Thanks again and wish me luck. I’m about to take my first Prozac dose now. I would welcome a followup post.

  12. My 14 year old step daughter is on zoloft and she is still having mood swings and still wanting to cut herself. Expecally everytime she gets around her mother. I was woundering if she would be better off taking the prozac instead.She also see’s a theripist. thanks, Jenny

  13. my gosh CS, i am so so sorry to hear about your losses. I just lost my 5 month old baby (in utero) to chromosomal problems and am being put on prozac for the post traumatic stress, etc. i am just so sad for you. I am so sorry.

  14. josephine waites

    I have a friend you takes zoloft, prozac and trazodone all together.  I am sure this is wrong but her psychiatrist prescribed them for her her.  What do you think.


  15. josephine waites

    My heart goes out to you CS.  I can not imagine what you and your family are going through.  Life can be so cruel sometimes.  God bless you and yours.


  16. you can’t say it alote of their effect is from a plocebo then say its a powerful medication. This is a brake from logic. So maby alote of the side effects are a plocebo. SSRI’s are helpful to most people. Haveing a real mental disorder takes real medication and CBT/Therapy. They have shown modert depression can be treted with arobic excersise and fish oil but it ends at modert depression. after that SSRIs are needed. My wife takes these zolft for OCD/Deprssion and it has given her life. (no real side effects) Most side effects will go away after you get used to the medication.

  17. I just switched from Zoloft to Prozac. The reason: Zoloft gave me incredibly painful acid reflux. Not all the time, but at least once or twice a month. The first time was so bad I thought I was having a heart attack and went to the ER. My doctor gave me Omeprazole to help with the acid reflux, but it didn’t always do the job. One psychiatrist told me that acid reflux is a common complaint among Zoloft users. I just took my first Prozac and I’m hoping that it will work as well as the Zoloft minus the acid reflux. I know Zoloft was working for me, because I stopped taking it for a couple of weeks and became absolutely miserable, felt hopeless and very depressed. As soon as I started taking it again, I felt much better.

    I hope that helps some people. I realize the article above was not very helpful, it basically said well on one hand it could do this, but on the other hand it may not. As I said, not very helpful. The only way that I’ve truly learned about various medications is from what people who are actually TAKING them have to say about them. You can read all the skewed data that is regurgitated about various medications, but the real answers can be found in the FORUMS, where real people leave real results.

  18. can prosaz be use for pain? i have ra and need frleif.

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