Zoloft (Sertraline) vs Prozac (Fluoxetine): Which is More Effective?

Prozac®, which contains the active ingredient fluoxetine, and Zoloft®, which contains sertraline, are two of the most widely used antidepressants available today. 

Prozac and Zoloft are both selective serotonin reuptake inhibitors, or SSRIs. Both medications work by changing the level of serotonin — a neurotransmitter that’s linked to depression — that’s present in your brain.

We’ve explained more about how SSRIs work in our full guide to selective serotonin reuptake inhibitors (SSRIs).

If you’ve been diagnosed with depression or one of several other conditions, your healthcare provider may recommend using Prozac, Zoloft or a similar medication.

Below, we’ve explained how Prozac and Zoloft work, as well as the main differences between these two medications. We’ve also listed side effects, drug interactions and other information that you should be aware of before using either medication. 

Prozac (Fluoxetine) vs. Zoloft (Sertraline): The Basics

  • Prozac and Zoloft are both antidepressants of the selective serotonin reuptake inhibitor (SSRI) class.

  • Both medications are approved for use as treatments for depression. They may also be prescribed for other disorders, such as panic disorder or obsessive-compulsive disorder (OCD). Both medications are also prescribed off-label to treat numerous conditions. 

  • Since both medications are SSRIs, Prozac and Zoloft tend to cause similar side effects and can interact with similar medications.

  • Prozac and Zoloft are both available as generic medications, meaning they’re typically very affordable. Prozac contains the active ingredient fluoxetine, while Zoloft contains sertraline.

  • Prozac and Zoloft can both cause antidepressant withdrawal if stopped suddenly. If you are prescribed either medication, it’s important that you talk to your healthcare provider before making any changes to your dosage or discontinuing your medication.

Indications and Uses

As SSRIs, Prozac and Zoloft are prescribed to treat similar conditions, albeit with a few small differences and special uses for each drug. 

Prozac and Zoloft are both prescribed to treat major depressive disorder (depression, or MDD), panic disorder and obsessive-compulsive disorder (OCD).

Prozac is also prescribed to treat the eating disorder bulimia nervosa. In combination with the antipsychotic medication olanzapine, it’s also prescribed to treat treatment resistant depression and acute depressive episodes associated with bipolar I disorder.

Zoloft is also prescribed to treat post-traumatic stress disorder (PTSD) and social anxiety disorder (SAD).

Both medications are occasionally prescribed off-label to treat other conditions. For example, generic sertraline — the active ingredient in Prozac — is commonly prescribed off-label to treat premature ejaculation

Use in Children and Teenagers

Prozac and Zoloft have both been approved by the FDA for use in children and teenagers for certain conditions: 

  • Prozac, or generic fluoxetine, can be prescribed to children eight years of age or older as a treatment for major depressive disorder, and to children seven years or older as a treatment for obsessive compulsive disorder (OCD).

  • Zoloft, or generic sertraline, can be prescribed to children six years of age or older as a treatment for obsessive compulsive disorder (OCD).

However, it’s important to note that the FDA has issued black box warnings for both Zoloft and Prozac, noting that both medications may increase the risk of suicidal thoughts in children, adolescents and young adults. They also insist parents, guardians and healthcare providers monitor these age groups closely for an increase in, or worsening of, suicidal thoughts. 

Side Effects of Prozac (Fluoxetine) and Zoloft (Sertraline)

Prozac and Zoloft can both cause side effects. As with other SSRIs, the most common side effects of Prozac and Zoloft aren’t serious. However, although uncommon, both medications may potentially cause severe side effects and interactions that you should be aware of.

Side Effects of Prozac (Fluoxetine)

Common side effects of Prozac and generic fluoxetine (affecting five percent of users or more and twice as many users as a non-therapeutic placebo) include:

  • Abnormal dreams
  • Abnormal ejaculation
  • Anorexia
  • Anxiety
  • Asthenia (loss of strength and energy)
  • Diarrhea
  • Dry mouth
  • Dyspepsia (indigestion)
  • Flu syndrome (fever, chills, headache and other flu-like symptoms)
  • Impotence (erectile dysfunction)
  • Insomnia
  • Nausea 
  • Nervousness
  • Pharyngitis (sore throat)
  • Rash
  • Reduced libido
  • Sinusitis (inflammation of the sinuses)
  • Somnolence (sleepiness or drowsiness)
  • Sweating
  • Tremor
  • Vasodilation
  • Yawning

Side Effects of Zoloft (Sertraline)

Common side effects of Zoloft and generic sertraline (affecting five percent of users or more and twice as many users as a non-therapeutic placebo) include:

  • Decreased appetite
  • Diarrhea
  • Difficulty or inability to ejaculate
  • Dyspepsia (indigestion)
  • Hyperhidrosis (excessive sweating)
  • Nausea
  • Reduced libido
  • Tremor

Serious Side Effects and Drug Interactions

Prozac and Zoloft are generally safe medications for most people. However, all antidepressants carry some risk of causing serious side effects. 

One potential side effect that’s important to be aware of is an increased risk of suicidal thoughts and behavior in children, teenagers and young adults. Prozac and Zoloft both carry a mandatory FDA warning notifying users of this risk in people aged 24 and under.

This risk is most significant during the first few months of treatment, or after changes are made to the medication’s dosage. 

Both medications may cause serotonin syndrome — a serious, potentially life-threatening side effect that can occur when they are used with other medications or supplements that increase serotonin levels.

As SSRIs, both medications can also cause issues such as abnormal bleeding, or an increased risk of bleeding, particularly when used with certain blood thinners or NSAIDs.

Both medications can also interact with other drugs, including other antidepressants and widely used prescription medications.

Use During Pregnancy and Breastfeeding

Prozac and Zoloft, as well as their generic equivalents, are both classed as pregnancy category C medications. 

This means that animal reproduction studies have shown adverse effects on fetuses, and that there is inadequate research regarding their safety in humans. However, the potential benefits of these medications may warrant their use during pregnancy in certain circumstances.

If you are pregnant or breastfeeding, or plan to become pregnant in the future, it’s important to inform your healthcare provider  if you’re currently prescribed Prozac (fluoxetine) or Zoloft (sertraline). 

Which Medication Is More Effective?

Prozac (fluoxetine) and Zoloft (sertraline) are both effective at treating depression. Research, including several studies, has shown that both medications produce improvements in people with major depression and anxious depression.

One study specifically tested the clinical efficacy of fluoxetine, sertraline and another antidepressant, paroxetine, in 104 patients experiencing major depression and anxious depression, and found no significant differences in the effectiveness of each medication. 

Another meta-analysis of 132 randomized controlled trials found that fluoxetine was slightly less effective than sertraline, but researchers also noted that although statistically significant, the clinical meaning of those differences is still uncertain. 

As mentioned above, Prozac and Zoloft are also prescribed to treat several other disorders and conditions. If you’re being treated for something other than depression, one medication may be a more suitable choice than the other. 

While Prozac and Zoloft have similar side effects, specific side effect rates can differ from one medication to the other. If you get persistent or severe side effects from one medication, your healthcare provider may recommend switching to the other, or to a different antidepressant.

There’s no “best” antidepressant for everyone. It’s normal and common to try several different antidepressants with your healthcare provider before settling on the medication that best suits your symptoms, needs and personal health. 

Frequently Asked Questions About Prozac and Zoloft

What Other Medications are Similar to Prozac and Zoloft?

Prozac and Zoloft are both selective serotonin reuptake inhibitors, or SSRIs. There are several other medications in this class, such as Paxil® (paroxetine), Lexapro® (escitalopram), Celexa® (citalopram) and others. 

Our guide to SSRIs goes into more detail about antidepressants of this type and lists a range of other medications similar to Prozac and Zoloft. 

Can Prozac or Zoloft Cause Weight Gain?

Many antidepressants are associated with weight gain. As SSRIs, both Prozac and Zoloft are less likely to cause significant weight gain than older types of antidepressant, such as tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs). 

In a 2016 study, researchers found that people prescribed fluoxetine and sertraline both gained a small amount of weight (4.6lbs for fluoxetine and 10.5 for sertraline) over the course of two years of treatment.

A separate study published in 2018 found that several of the most commonly prescribed SSRIs and other antidepressants, including the active ingredients in Prozac and Zoloft, caused a higher risk of weight gain during treatment.

In short, antidepressants, including Prozac and Zoloft, can cause weight gain. However, not all people who are prescribed antidepressants will gain weight. 

If you are concerned about weight gain while using either antidepressant, talk to your healthcare provider. If suitable for you, your healthcare provider may be able to prescribe an antidepressant that’s less likely to cause weight gain. 

Is it Safe to Drink Alcohol While Using Prozac or Zoloft?

Drinking alcohol while you use either Prozac or Zoloft is not recommended. The FDA labels for both medications specifically recommend not to drink alcohol while you are being treated with either medication.

In addition to affecting medication, drinking alcohol may increase your risk of experiencing side effects and/or worsen your depression.

What Else Should Be Avoided While Using These Medications?

Both Prozac and Zoloft can affect your ability to make decisions, think clearly or react quickly. If you are prescribed either medication, it’s important not to drive, operate heavy machinery or do any other potentially dangerous tasks until you understand how the medication affects you.

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This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.