Zoloft vs. Prozac: Differences, Similarities and Which One Is Right for You?

By Irmanie Hemphill, MD, FAAFP
Medically reviewed
August 2, 2021

Prozac and Zoloft are brand-name medications used to treat depression, anxiety, and other mental health conditions.

They are among a handful of antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs) that work by improving your brain chemistry to boost your mood, regulate your emotions, and enhance the quality of your sleep.

Lexapro and Celexa are other commonly prescribed SSRIs.

Healthcare providers have used antidepressant medications to treat patients for decades. Prozac was the first SSRI approved for patient use in 1988, and Zoloft became available for U.S. patients in 1991.

Their generic forms, fluoxetine and sertraline hydrochloride, have been approved for patient use for more than fifteen years.

Today, antidepressants, particularly SSRIs like Prozac and Zoloft, are some of the most commonly prescribed medications in the United States.

More than 13% of Americans over the age of 12 have taken an antidepressant within the last month.

Though Prozac and Zoloft are part of the same class of medications, there are critical differences between them. They come in varying forms, dosage strengths and can be used to treat different conditions.

In this article, I will cover the difference between Zoloft and Prozac, and which conditions each drug can be used to treat. I’ll discuss which is more effective, and which drug is better for anxiety and social anxiety disorders.

I’ll also list some of the side effects of each drug, and explain whether you can take them together, or take them while pregnant.

I’ll cover how long you need to take each drug, harmful interactions that can happen if you’re taking other drugs, and warnings about both Zoloft and Prozac.

Finally, I’ll discuss the cost and availability of each drug, whether you can get them online, and how to talk to a doctor about whether either medication is right for you.

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What is the Difference Between Zoloft vs. Prozac?

Prozac and Zoloft are both prescription drugs approved for the treatment of depression, anxiety, and other mental health conditions.

Both increase serotonin levels in your brain, helping you to improve your mood, sleep, appetite, and quality of life. But they are not the same drug. 

Differences between the two medications include:

  • Form: Prozac is available as a capsule, tablet, or in a concentrated solution. Zoloft is only available in tablet or solution form. 
  • Dosage: Prozac is available in various dosages, from 10-90 mg, depending on its form. Zoloft is available in 20 mg as a concentrated solution or in a range of dosages from 25-100 mg in tablet form. The standard adult dosage of Prozac is 20 mg. Zoloft’s is 50mg.
  • Use for pediatric patients: Only Prozac is approved to treat major depressive disorder (MDD) in children and adolescents. Doctors often prescribe Prozac or Zoloft to treat obsessive-compulsive disorder (OCD) in patients under 18.

What Conditions are Treated by Zoloft and Prozac?

The Food and Drug Administration (FDA) has approved Prozac to treat mental health conditions like major depression (MDD), obsessive-compulsive disorder (OCD), panic disorder, and treatment-resistant depression.

In addition, doctors will sometimes prescribe it in combination with other medications to treat patients with bipolar disorder. 

Some healthcare professionals prescribe Prozac “off-label” to treat general anxiety, post-traumatic stress disorder (PTSD), social anxiety disorder, body dysmorphic disorder, bulimia nervosa, and binge eating disorder.

It is also used to treat premenstrual dysphoric disorder (PMDD) under a different brand name, Sarafem.

Zoloft is approved to treat MDD, PTSD, panic disorder, OCD, social anxiety (SAD), and PMDD.

In addition, doctors will sometimes use it “off-label” to treat binge eating disorder, body dysmorphic disorder, and general anxiety.

Which is More Effective?

Both Prozac and Zoloft are considered powerful mental health medications, comparably effective at treating depression and reducing anxiety for the patients who take them.

A few clinical trials suggest that Zoloft may have less serious side effects than Prozac. It also may be slightly better at treating severe depression.

If you have questions about whether you should be taking Prozac, Zoloft, or another anti-depression medication, seek medical advice from a healthcare professional to learn if one may be right for you.

Which is Better For Anxiety and Social Anxiety?

Antidepressant medications like Prozac and Zoloft can offer patients relief from symptoms related to anxiety, but effectiveness can vary depending on the individual, dosage, and condition treated.

Both Prozac and Zoloft are approved to treat panic disorders and are used “off-label” to treat general anxiety disorder, or GAD. However, only Zoloft is FDA-approved to treat social anxiety and PTSD. 

Side Effects of Zoloft and Prozac

Although SSRI medications like Prozac and Zoloft often have similar side effects, patient experiences on these drugs are not always the same. Common side effects of Prozac include:

  • Nausea, indigestion, and diarrhea
  • Loss of appetite, weight loss, and anorexia
  • Dry mouth and sore throat 
  • Muscle weakness, tremor, or drowsiness 
  • Nervousness and anxiety
  • Sexual dysfunction including decreased libido, impotence, and abnormal ejaculation for men
  • Insomnia and abnormal dreams 
  • Decreased blood pressure 

The most common side effects of Zoloft include: 

  • Nausea, indigestion, and diarrhea
  • Loss of appetite, weight loss, and anorexia
  • Excessive sweating
  • Muscle tremor 
  • Sexual dysfunction including decreased libido and ejaculation failure for men

Both medications carry the rare but serious risk of increasing suicidal thoughts and behaviors in teenagers and young adults.

If you or someone you know is at risk of harming themselves or others, call 9-1-1 or go to the nearest emergency room immediately.

Prozac vs. Zoloft Weight Gain

There is not much research on how Prozac, Zoloft, or other SSRI medications affect long-term weight.

One study suggests that many patients lose weight after they begin taking antidepressant medication.

Researchers suggest that those who gain weight do so because they eat more nutritiously after being medicated for depression.

Can You Take Them Together?

No. Do not take Prozac and Zoloft together.

Taking both medications will not increase their efficacy or make them work more quickly; it will only put you at an increased risk for adverse effects.

Taking more than one SSRI can result in a dangerous reaction called serotonin syndrome.

Symptoms of this syndrome include heart palpitations, confusion, vision changes (glaucoma), and seizures. You should be evaluated in the emergency room right away if they occur. 

If you are concerned about whether your antidepressant drug is working for you, talk to your doctor. They may recommend changing your dosage or medication to something that will work better for your case.

Can You Take Them While Pregnant?

It’s crucial to balance your mental health needs with the physical well-being of your unborn child.

If you are experiencing depression while pregnant or breastfeeding, talk to your doctor about whether or not taking an SSRI medication is right for you. 

Women with untreated depression may not receive adequate nutrition or seek prenatal care, putting their babies at risk for long-term health consequences.

On the other hand, women who take antidepressant medications while pregnant, particularly while in their third trimester, may increase the risk of their child having withdrawal symptoms after they are born.

In very rare cases, children exposed to SSRIs while in utero can develop persistent pulmonary hypertension, a condition that affects the lungs.

A few studies have also linked the use of SSRI medications (particularly one called paroxetine) during pregnancy with the increased risk of cardiac conditions in infants.

How Long Do You Need to Take Them?

Everyone reacts to medications differently.

For example, some people take antidepressant medications for a few weeks or months; others may take them much longer. 

How long do they take to work?

Some patients report an improvement in their mood and outlook in as little as two weeks of regularly taking their SSRI medications.

But for most patients, SSRIs take 4-8 weeks to provide relief. 

If you have taken Prozac and Zoloft for at least eight weeks and are experiencing no change or worsening symptoms, talk to your doctor about adjusting your dosage or medication entirely.

SSRI medications carry a risk of withdrawal symptoms, including sore throat, nausea, insomnia, and hallucinations. Do not stop taking your medicine without talking to your doctor about how to wean off the drugs safely.

Drug Interactions

Both Prozac and Zoloft can react poorly with other prescription medications, over-the-counter drugs, and homeopathic remedies.

If you are taking Prozac or Zoloft—or would like to begin— talk to your doctor about all of the substances you take. Do not take an SSRI medication if you are taking: 

  • Amphetamines
  • Anticoagulants
  • Buspirone
  • Fentanyl
  • Lithium
  • Monoamine oxidase inhibitors (MAOIs)
  • St. John’s wort
  • Tricyclic antidepressants (TCAs)
  • Tramadol
  • Triptans
  • Tryptophan
  • Warfarin or other blood thinners

Taking non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin when you are on SSRI medications can increase your risk of excessive bleeding and bruising. 

In rare cases, patients who take Prozac or Zoloft along with certain antibiotics and anti-arrhythmic drugs can develop long QT syndrome or an irregular heart rhythm. 

If you are taking Prozac or Zoloft and have any abnormal symptoms, including agitation, anxiety, restlessness, racing heart, sweating, high fever, high blood pressure, or confusion, seek medical help immediately.

You may be experiencing serotonin syndrome, a rare but life-threatening condition that occurs when a drug interaction makes too much serotonin available in your brain.

Warnings

Zoloft and Prozac offer relief from symptoms related to depression, anxiety, and other mental health conditions for most patients.

But each carries the risk of adverse drug interactions, serotonin syndrome, and increased suicidal thoughts and behaviors, particularly for young people.

If you believe you might benefit from an antidepressant medication like Zoloft or Prozac, talk to a healthcare professional about whether an SSRI is suitable for you.

If you are currently taking Zoloft or Prozac and are experiencing suicidal thoughts or behaviors, an irregular heart rhythm, or any symptom that could be related to serotonin syndrome, call 9-1-1 or seek emergency medical help immediately.

Cost and Availability

Both Prozac and Zoloft and their generic forms, fluoxetine and sertraline hydrochloride, are available with a prescription from a health care provider.

Out-of-pocket costs can vary, depending on an individual’s dosage, insurance coverage, and pharmacy location. Ordering your prescription medication through safe pharmacy services online may help keep your drug costs under control.

Can You Get Zoloft or Prozac Online? 

Yes. As long as you have a prescription from a doctor, you can legally purchase Zoloft, Prozac, or other medications online.

Ordering your prescription medication online can cost less, and will let you receive your medication through convenient home delivery. If you are looking for a trustworthy online pharmacy, K Health is a great place to start.

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Frequently Asked Questions

What is Zoloft?
Zoloft is a brand-name prescription drug that is used to treat depression, anxiety disorders, and other mental health conditions. It is part of a class of medications called selective serotonin reuptake inhibitors (SSRIs). These medications work by improving your brain chemistry to boost your mood, regulate your emotions, and enhance the quality of your sleep. It is also available as a generic medication called sertraline hydrochloride.
What is Prozac?
Prozac is a brand-name prescription drug that is used to treat depression, obsessive-compulsive disorder, certain eating disorders, and certain types of anxiety. It is an SSRI medication just like Zoloft, Lexapro, and Celexa, among others. It is available as a generic medication called fluoxetine.
Zoloft vs. Prozac, which is safest?
Research has shown that Zoloft and Prozac are comparably effective when treating most patients with depression. Only Prozac is approved to treat major depressive disorder (MDD) in children and adolescents.
Prozac vs. Zoloft for OCD?
Both Prozac and Zoloft are FDA-approved for use to treat patients with obsessive-compulsive disorder (OCD).
Zoloft vs. Prozac, which is better?
Antidepressant medications like Prozac and Zoloft can offer patients relief from symptoms related to depression, anxiety, and other mental health conditions, but drug effectiveness can vary depending on the individual patient, dosage, and the condition that is being treated.
K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

K Health has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. We avoid using tertiary references.

Irmanie Hemphill, MD, FAAFP

Dr. Hemphill is an award winning primary care physician with an MD from Florida State University College of Medicine. She completed her residency at Halifax Medical Center.