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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