Prozac (Fluoxetine) vs. Zoloft (Sertraline): Which Is Right For You?

Medically reviewed by Alex Yampolsky, PharmD

Prozac (fluoxetine) and Zoloft (sertraline) belong to the same drug class called selective serotonin reuptake inhibitors (SSRIs). Both medications help treat many mental health conditions, including depression and anxiety.

Zoloft and Prozac share some uses but differ in others. For example, the Food and Drug Administration (FDA) approved Zoloft to help manage some mental health conditions that Prozac is not used for, including social anxiety and post-traumatic stress disorder (PTSD).

Unlike Zoloft, Prozac is approved to help with treatment-resistant depression and bulimia nervosa.

This article will help you understand the main differences and similarities between Prozac and Zoloft in treating depression and anxiety, which one works better, side effects, interactions, and more.

Similarities Between Prozac and Zoloft

Prozac and Zoloft are both in the same drug class called SSRIs.

Both medications work by preventing the reuptake of serotonin storage in nerve cells of the brain. As a result, more serotonin is available to transport chemical messages between neurons.

While increasing serotonin levels can be beneficial in managing your anxiety and depression, high levels of serotonin can put you at risk of serotonin syndrome.

The FDA approved Prozac and Zoloft to help manage:

• Major depression disorder

• Obsessive-compulsive disorder (OCD)

• Panic disorder

• Premenstrual dysphoric disorder

In addition, both medications have similar off-label use to help manage binge eating, body dysmorphia, and general anxiety disorder.

Common side effects seen in both medications include nausea, diarrhea, and trouble sleeping.

How Do SSRIs Work?

SSRIs help treat depression and anxiety by increasing serotonin levels in your brain. Serotonin is a chemical stored and released to provide feel-good signals in the brain.

SSRIs can increase serotonin in your brain by preventing the reuptake of serotonin back into your neurons. Therefore, more serotonin is available to carry signals between neurons and provide the sensation of happiness.

Differences Between Prozac and Zoloft

The main differences between Prozac and Zoloft are based on what mental health conditions they can help manage.

In addition to its above uses, Prozac is approved to help with:

• Bulimia nervosa

• Treatment-resistant depression

• Depression and bipolar in combination with Zyprexa (olanzapine)

Unlike Prozac, Zoloft is approved to help with social anxiety and PTSD.

In addition to daily dosing, Prozac is available as a once-weekly dose for depression only.

However, Zoloft is only available to be taken once a day. So if you take either Prozac or Zoloft for depression and struggle to remember your medications, Prozac dosed weekly may be a better option.

Is Prozac or Zoloft More Effective?

Prozac and Zoloft share similar uses, How effective they are comparatively may vary based on the type of mental health condition.

Major Depressive Disorder

A study was conducted among about 500 people to compare the effectiveness of Prozac, Zoloft, and Paxil (paroxetine) in preventing depressive episodes. They were treated with one of these medications for at least three months.

According to the results, all three SSRIs worked the same in helping reduce depression.

General Anxiety Disorder

A review of 30 evaluated the effectiveness of various SSRIs, including Prozac and Zoloft, in treating general anxiety disorder. The studies included more than 13,000 participants.

The study concluded that Prozac was more effective in reducing anxiety. However, those who took Zoloft experienced fewer side effects.

Obsessive-Compulsive Disorder (OCD)

A review of multiple studies compared the effectiveness of going to therapy or SSRIs can help improve OCD.

The study concluded that all SSRIs, which include Prozac and Zoloft, provide the same effectiveness in treating OCD. In addition, the combination of going to therapy and taking medications provides the most benefit for managing OCD.

Panic Disorder 

Since both Prozac and Zoloft are approved to help prevent panic attacks, they are both equally effective in managing panic disorder.

What Are the Side Effects of Prozac vs. Zoloft?

Some common side effects that both Prozac and Zoloft share are listed below:

• Nausea

• Diarrhea

• Dizziness and weakness

• Headache

• Trouble sleeping

Side effects most frequently seen with Prozac only include:

• Strange dreams

• Nervousness

• Yawning

• Nose or throat irritation

Side effects most frequently seen with Zoloft only include:

• Dry mouth

• Increased sweating

While Prozac and Zoloft are clinically safe to use, you must be cautious of serious side effects that may occur. Contact your healthcare provider immediately if you experience any of these side effects.

Severe side effects that both Prozac and Zoloft share include:

• Signs of an allergic reaction (e.g., hives, trouble breathing, swelling of the face, lips, tongue)

• Signs of low sodium levels such as memory problems, feeling confused, or change in balance

• Signs of serotonin syndrome such as hallucinations, twitching, or seizures

• Sudden weight gain or loss

• Abnormal heartbeat

Severe side effects seen in Prozac only include:

• Feeling anxious or experiencing panic attacks

• Trouble controlling body movements

Severe side effects seen in Zoloft only include:

• Throwing up or coughing blood

• Severe skin reactions such as blisters, peeling skin, red eyes, or sores in the mouth

Prozac vs. Zoloft Interactions

Since Prozac and Zoloft are both SSRIs, they have similar drug interactions.

Avoid taking the following with Prozac or Zoloft:

• Other antidepressants, such as other SSRIs, monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants

• St. John's wort

• Blood thinners

• Medications that affect heart rhythm

Taking other substances that increase serotonin (e.g., antidepressants, St. John's wort) with Prozac or Zoloft can put you at risk of serotonin syndrome, a potentially life-threatening condition characterized by too much serotonin in the body.

Too much serotonin can lead to seizures, high fever, or hallucinations.

Examples of common antidepressants include:

• Nardil (phenelzine)

• Amitriptyline

• Lexapro (escitalopram)

• Cymbalta (duloxetine)

Prozac and Zoloft can increase the risk of bleeding. If you take blood thinners along with Prozac or Zoloft, your risk of bleeding further increases.

Common blood thinners include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as Advil (ibuprofen) and Aleve (naproxen)

• Anticoagulants, such as Pradaxa (dabigatran), Xarelto (rivaroxaban), and Eliquis (apixaban)

• Antiplatelet drugs, such as Plavix (clopidogrel) and Effient (prasugrel)

Prozac and Zoloft can increase the risk of an abnormal heart rhythm. Combining the medications below can increase the risk of an abnormal heart rhythm.

• Certain antibiotics, such as Cipro (ciprofloxacin) and Zithromax (azithromycin)

• Diflucan (fluconazole)

• Haldol (haloperidol)

• Geodon (ziprasidone)

Summary

Prozac and Zoloft are SSRIs commonly prescribed for anxiety and depression. Both work by increasing serotonin levels in the brain, providing feel-good effects to combat symptoms of depression and anxiety.

Both medications provide the same effectiveness in preventing depressive episodes. However, Prozac is generally more effective in treating general anxiety disorder, whereas Zoloft is more effective in treating PTSD and social anxiety.

Prozac and Zoloft share similar side effects and safety profiles, including the risk of serotonin syndrome. Tell your healthcare provider about any over-the-counter (OTC) or prescription medications, herbal supplements, or vitamins you are taking to prevent unwanted drug interactions.

Frequently Asked Questions

Does Zoloft or Prozac work faster?

Zoloft and Prozac work at the same rate in improving symptoms of anxiety or depression. You may notice partial symptom improvement in as few as two weeks, although it can take longer. You may not feel the full effects until one to two months of consistent use.

Is Zoloft or Prozac stronger?

When comparing Prozac and Zoloft, one medication is not necessarily stronger than the other. The effectiveness of each medication depends on what mental health condition you have.

If you have general anxiety, Prozac may be the better option for reducing symptoms, whereas Zoloft may be more suitable for social anxiety. Both Prozac and Zoloft should help manage your depression symptoms similarly.

How do I know whether Zoloft or Prozac is better for me?

Based on what health condition you have, your healthcare provider will choose the right medication for you. In addition, symptoms and responses to treatment vary from person to person. If you feel Prozac or Zoloft is not working well for you, contact your healthcare provider to find the best fit.

The author would like to recognize and thank Alexya Rosas for contributing to this article.