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Prozac vs Zoloft - What are the Differences & Similarities?

Medically reviewed by Carmen Pope, BPharm. Last updated on July 20, 2022.

Official answer


Both Prozac and Zoloft belong to the class of medicines called selective serotonin reuptake inhibitors (SSRIs) and are FDA approved to treat depression, OCD (obsessive-compulsive disorder), and panic disorder.

The main differences between Prozac and Zoloft are:

  • Prozac is a branded version of fluoxetine and Zoloft is a branded version of sertraline
  • Prozac is also FDA approved to treat Bulimia nervosa and bipolar disorder associated depression
  • Zoloft is also FDA approved to treat PTSD (post-traumatic stress disorder), social anxiety disorder, social phobia, and premenstrual dysphoric disorder (PDD)
  • Prozac is available as a tablet, capsule, delayed-release capsule and liquid. Zoloft is only available as a tablet and a liquid
  • There are some differences in their side effects with Prozac being more likely to cause sleep problems and dry mouth, and Zoloft is more likely to cause diarrhea
  • Prozac was FDA approved in 1987 and Zoloft was FDA approved in 1991.

Because both drugs are SSRIs, they have many similarities, such as:

  • They both work by preventing the reuptake of serotonin, a chemical in the brain that acts as a messenger between nerve cells. SSRIs increase levels of serotonin in the nerve synapse and this has been associated with a reduction in depressive symptoms
  • Research1 has shown that Prozac and Zoloft are equally effective for the treatment of depression with similar rates of adherence (likelihood of a person taking their medicine)
  • Side effects, such as headache, nausea and vomiting, nervousness and anxiousness, dizziness, sexual problems (eg, erectile dysfunction) and weight gain (although this tends to be less than with other antidepressants) or weight loss are common to both Prozac and Zoloft. Both have been associated with withdrawal symptoms when discontinued
  • Both are branded drugs; however, generics are available for each drug which makes costs similar
  • Both are prescription medicines and neither is a controlled drug
  • The likelihood of interactions with other drugs (such as monoamine oxidase inhibitors, pimozide, tramadol, St John’s wort) is similar.
  1. Kroenke K, West SL, Swindle R, et al. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA. 2001 Dec 19;286(23):2947-55.

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