Prozac vs. Zoloft: What’s the Difference?

Published on: 03 Apr 2023
Clinically Reviewed by Ashley Ertel, LCSW, BCD
Prozac vs. Zoloft

Prozac and Zoloft are commonly prescribed medications for treating mental health conditions like depression and anxiety. Both drugs belong to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs.)  

Differences Between Prozac vs Zoloft

The main difference between Zoloft and Prozac is their half-life — the time it takes for each antidepressant drug to leave your system after you take it. The half-life of Prozac is longer than that of Zoloft. If you miss a dose or stop taking either antidepressant medication abruptly, the effects may last longer with Prozac than with Zoloft. 

Both drugs might cause weight changes. However, the main difference between Zoloft and Prozac is that research suggests weight gain might be more pronounced with Prozac than Zoloft weight gain

Finally, when taken during pregnancy or breastfeeding, there may be an increased risk for congenital disabilities associated with using Prozac compared to other SSRIs. Taking Zoloft during pregnancy tends to be the safest antidepressant option.

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Conditions they treat

Zoloft and Prozac were first approved to manage symptoms of depression.

Aside from being a medication for depression, the FDA also approved Zoloft to treat other conditions, including: 

Zoloft can also be used off-label to treat anxiety, body dysmorphia, and binge eating disorder. 

Prozac is approved to treat

  • Treatment-resistant depression
  • Obsessive-compulsive disorder
  • Panic disorder 
  • Bulimia nervosa

Sometimes, Prozac is used in combination with other drugs to treat bipolar disorder.  

Is Zoloft better for anxiety symptoms than Prozac?

Both drugs can effectively treat anxiety disorders such as social anxiety or generalized anxiety disorder (GAD). However, there isn’t conclusive evidence that one is better than the other for treating symptoms of anxiety

Some research suggests that Zoloft and Prozac have equal efficacy in treating major depression with high anxiety. Talk with your doctor about which medication might be best to treat your anxiety symptoms

Dosage amount

The recommended dosage amount varies depending on the condition and factors like age or weight. Most doctors start people off at lower doses when prescribing either antidepressant drug, then gradually increase the amount if needed. It’s important not to exceed the recommended dose without consulting your doctor first, since doing so could lead to serious side effects or even an overdose. The typical dosage for each is:

  • Prozac – Starting: 20mg/day; Maintenance: 20 – 60 mg/day
  • Zoloft – Starting: 50mg/day; Maintenance: 50 – 200 mg/day

Who can take Prozac vs Zoloft

When looking at Zoloft versus Prozac, both medications are generally considered safe for adults. Potential risks are associated with use in younger people, including suicidal thoughts or behavior changes. Pregnant women should avoid taking these drugs unless they discuss them with their doctor first. Likewise, breastfeeding women should discuss these drugs with their doctor.

Side effects

Common Prozac and Zoloft side effects include nausea, headache, insomnia, dry mouth, sexual dysfunction, fatigue, drowsiness, and agitation/anxiety. 

More severe common side effects may include an increased risk of suicide attempts in young adults and seizures or allergic reactions that require immediate medical attention. 

If any unusual symptoms occur while taking either medication, talk to your healthcare provider immediately so they can adjust your dosage if needed.

Similarities Between Prozac vs Zoloft

Both Prozac and Zoloft are used to treat depression, anxiety, and other mental health conditions. They’re similar in efficacy, and both work by increasing serotonin in the brain. Serotonin is a neurotransmitter that’s associated with mood. Prozac and Zoloft are available by prescription. Neither is a controlled substance. 

“Both are similar categories of medication by classification SSRIs, prescribed for mood and anxiety disorders. FDA approval and indication for both medications to treat disorders are different. Major depression, obsessive-compulsive disorder (OCD), and panic disorder can be treated with Prozac. Zoloft is often for post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), social anxiety disorder, or social phobia.”

Talkspace psychiatrist Dr. Muhammad Munir

Drug Interactions

There are some prescription drugs, over-the-counter medicines, and homeopathic remedies that Prozac and Zoloft are known to react poorly with.

Discuss all your medications with your doctor if you’re taking Prozac or Zoloft. If used with SSRI medications, aspirin or ibuprofen may cause excessive bleeding or bruising. Prozac and Zoloft can occasionally cause long QT syndrome or irregular heart rhythms in some people when taken with antiarrhythmic drugs or antibiotics. 

Other medications or substances known to have potential adverse drug interactions with Prozac and Zoloft include:

  • Buspirone
  • Lithium
  • Monoamine oxidase inhibitors (MAOIs)
  • St. John’s Wort
  • Tricyclic antidepressants (TCAs)
  • Triptans
  • Grapefruit 

Determine if Prozac or Zoloft Is Right for You with Talkspace

When it comes to treating mental health, there are a variety of medications available. Two commonly prescribed antidepressants are Prozac and Zoloft. Both drugs have similar effects on the brain. However, they also have some differences that can make one more suitable than the other for certain individuals. 

With Talkspace online psychiatry, you can get help determining which antidepressant medication is proper for you with a prescription. Get started with Talkspace today to get connected with a licensed psychiatrist.


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  2. Singh HK, Saadabadi A. Sertraline – StatPearls – NCBI Bookshelf. Sertraline. Published May 2, 2022. Accessed December 17, 2022.
  3. Sohel AJ, Shutter MC, Molla M. Fluoxetine – StatPearls – NCBI Bookshelf. Fluoxetine. Published July 4, 2022. Accessed December 17, 2022. 
  4. ZOLOFT (sertraline hydrochloride) Label – Food and Drug Administration (FDA). Accessed December 17, 2022.
  5. Prozac (fluoxetine hydrochloride) capsules label – Food and Drug Administration (FDA). Accessed December 17, 2022.
  6. Sechter D, Troy S, Paternetti S, Boyer P. A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients. European Psychiatry. 1999;14(1):41-48. doi:10.1016/s0924-9338(99)80714-7. Accessed December 17, 2022.
  7. Cooper WO, Callahan ST, Shintani A, et al. Antidepressants and suicide attempts in children. Pediatrics. 2014;133(2):204-210. doi:10.1542/peds.2013-0923. Accessed December 17, 2022.

Talkspace articles are written by experienced mental health-wellness contributors; they are grounded in scientific research and evidence-based practices. Articles are extensively reviewed by our team of clinical experts (therapists and psychiatrists of various specialties) to ensure content is accurate and on par with current industry standards.

Our goal at Talkspace is to provide the most up-to-date, valuable, and objective information on mental health-related topics in order to help readers make informed decisions.

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