Prozac vs. Zoloft: Which Antidepressant is Right for Me?

Prozac vs Zoloft Overview

Introduction to SSRIs

If you have been diagnosed with depression or other mental health conditions such as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), or panic disorder, your healthcare provider may prescribe an antidepressant medication to treat your symptoms. 

A common category of antidepressants is called selective serotonin reuptake inhibitors or SSRIs. Two of the most widely prescribed antidepressants, Zoloft and Prozac, are  SSRIs. Other examples of SSRIs include paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro).

Brief Overview of Prozac (Fluoxetine)

Prozac (generic drug fluoxetine) is a selective serotonin reuptake inhibitor (SSRI) that is FDA-approved for: 

• Major depressive disorder (MDD) in adults and children 8 years of age and older.

• Obsessive-compulsive disorder (OCD) in adults and children 7 years of age and older. 

• Bulimia nervosa in adults.

• Panic disorder in adults.

Brief Overview of Zoloft (Sertraline)

Zoloft (generic drug sertraline) is a selective serotonin reuptake inhibitor (SSRI) that is FDA-approved for:

• Major depressive disorder (MDD) in adults.

• Obsessive-compulsive disorder (OCD) in adults and children 6 years of age and older.

• Post-traumatic stress disorder (PTSD) in adults.

• Panic disorder in adults.

• Social anxiety disorder in adults.

• Premenstrual dysphoric disorder (PMDD) in adults.

Mechanism of Action

Both Prozac and Zoloft work in the same way. They are selective serotonin reuptake inhibitors. These medications prevent the reuptake (reabsorption) of a neurotransmitter called serotonin. Serotonin is a natural chemical messenger in the brain that stabilizes mood, produces healthy sleeping patterns, and enhances feelings of well-being and happiness. 

Zoloft and Prozac prevent the reuptake of serotonin by making more serotonin available to nerve cells in the brain. This helps to boost mood, regulate emotions, and relieve depression. 

Notably, SSRIs do not help the body make more serotonin—they simply allow the body to use what is already made more effectively.

Zoloft vs Prozac: Key Differences

Here are some of the main differences between Prozac and Zoloft:

• Active ingredients: Zoloft contains sertraline and Prozac contains fluoxetine as the active ingredient.

• Manufacturer: Brand name Zoloft is made by the pharmaceutical company Pfizer. Brand name Prozac is manufactured by Eli Lilly.

• Age Approved: Zoloft is prescribed to adults. It can also be given to children 6 years of age or older for OCD. Prozac is used to treat major depressive disorder in adults and children 8 years of age and older and OCD in adults and children 7 years of age and older.

• Dosage forms: Zoloft is available as an oral tablet -25 milligrams (mg), 50 mg, 100 mg,  and oral solution -20 milligrams per milliliter (mg/mL). Prozac comes as an immediate-release capsule (20 mg, 30 mg, 40 mg) and a delayed-release oral capsule (90 mg).

• Usual dose: The typical dose of Zoloft (sertraline) is 50 mg per day. The usual dose of Prozac (fluoxetine) is 20 mg per day.

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Efficacy: Zoloft vs Prozac

Which is More Effective: Prozac or Zoloft?

Double-blind clinical trials have found Prozac and Zoloft are equally effective in treating depression. Both drugs can significantly improve symptoms of depression, anxiety, and sleep disturbances, as measured by different depression scales. 

However, one randomized controlled trial found that 19.6% of patients discontinued Prozac (fluoxetine) due to therapy failure (no improvement in symptoms). In contrast, only 9.6% of patients discontinued Zoloft (sertraline) due to ineffectiveness. This would suggest that Zoloft has an advantage over Prozac. 

Is Zoloft or Prozac Better for Panic Attacks?

Zoloft may be better for panic attacks compared to Prozac. A meta-analysis of studies on the drug treatment of panic attacks suggested that SSRIs are an effective treatment for panic disorder with a low risk of adverse events. Among the different SSRIs, sertraline (Zoloft) and escitalopram (Lexapro) were linked to the highest rates of remission and the lowest rates of adverse events.

Note that both Prozac and Zoloft can be used to treat panic attacks. Your doctor can provide medical advice, diagnosis, or treatment for panic attacks. 

The choice of antidepressant, Zoloft / Prozac, for panic disorder, will also depend on other co-occurring conditions. For instance, if you also have PTSD or social anxiety, Zoloft may be the preferred therapy because it is approved for these conditions in addition to panic attacks, whereas Prozac is used off-label (it is not FDA-approved) for social anxiety or PTSD.

Is Zoloft or Prozac Better for Obsessive-Compulsive Disorder (OCD)?

A meta-analysis of studies on the drug treatment of OCD suggested that there is no statistically significant difference among the different SSRIs in terms of efficacy for this mental health condition. In other words, both Prozac and Zoloft are effective in treating obsessive-compulsive disorder (OCD) in adults. In children with OCD, Zoloft can be prescribed to children 6 years of age and older and Prozac to children 7 years of age and older.

Is Prozac More for Anxiety or Depression?

Prozac is primarily an antidepressant, but it is also FDA-approved to treat certain anxiety disorders such as obsessive-compulsive disorder and panic disorder. 

Side Effects of Prozac

Common side effects of Prozac are listed below. Tell your healthcare provider if they are severe or persist after your body adjusts to Prozac.

• Nervousness, restlessness, or anxiety

• Insomnia

• Gastrointestinal side effects (heartburn, nausea, diarrhea)

• Loss of appetite 

• Weight changes

• Dry mouth

• Yawning

• Uncontrolled shaking

• Excessive sweating

• Stuffy nose

• Weakness 

• Unusual dreams

• Sexual problems in men and women

• Cognitive side effects such as confusion, difficulty concentrating, or memory problems

More serious side effects of Prozac are listed below. Seek emergency medical care if you develop: 

• Skin rash, hives, itching, peeling, or blistering skin

• Swelling of the face, eyes, lips, tongue, throat, hands, lower legs, ankles, or feet

• Changes in heartbeat (fast, slow, or irregular)

• Shortness of breath

• Difficulty breathing or swallowing

• Fever

• Joint pain

• Fever, sweating, shivering, confusion, agitation, hallucinations, fast or irregular heartbeat, severe muscle stiffness or muscle twitching, loss of coordination, nausea, vomiting, or diarrhea

• Dizziness or fainting

• Convulsions

• Abnormal bleeding or bruising

Side Effects of Zoloft 

Common side effects of Zoloft are listed below. Tell your healthcare provider if they are severe or persist after your body adjusts to Zoloft.

• Nervousness

• Dizziness

• Headache

• Insomnia

• Gastrointestinal side effects (heartburn, nausea, vomiting, diarrhea, constipation)

• Loss of appetite

• Weight changes

• Dry mouth

• Excessive fatigue

• Uncontrolled shaking

• Excessive sweating

• Sexual problems in men and women

More serious side effects of Zoloft are listed below. Seek emergency medical care if you develop:

• Skin rash, hives, itching, peeling, or blistering skin

• Swelling of the face, eyes, lips, tongue, throat, hands, lower legs, ankles, or feet

• Changes in heartbeat (fast, slow, or irregular)

• Shortness of breath

• Difficulty breathing or swallowing

• Fever, sweating, shivering, confusion, agitation, hallucinations, fast or irregular heartbeat, severe muscle stiffness or muscle twitching, loss of coordination, nausea, vomiting, or diarrhea

• Convulsions

• Abnormal bleeding or bruising

• Confusion, unsteadiness, memory problems

What Are The Risks of Taking Antidepressants?

Suicidal Risk on Antidepressants

SSRIs and other prescription drugs used to treat major depression are generally safe. In the long run, the right antidepressant can provide long-term benefits by boosting mood and improving overall quality of life. 

However, antidepressant drugs carry a black-box warning, which is the strictest warning for prescription medications by the FDA. All antidepressants, including SSRIs, can cause children, adolescents, and young adults below 25 years of age to have increased suicidal thoughts and behavior. This risk is especially high during the first few weeks of therapy and after dosage adjustments.

For this reason, close monitoring and check-ins are very important during treatment with Zoloft and Prozac. If you or a loved one experiences worsening depressive symptoms or has an increase in thoughts of self-harm, please contact the doctor immediately or get emergency help. 

Use During Pregnancy and Lactation

Tell your doctor if you are pregnant or breastfeeding before starting an antidepressant medicine. Prozac and Zoloft can cause problems in newborn babies if they are taken during the last few months of pregnancy. 

Withdrawal Symptoms

Stopping antidepressants can cause withdrawal symptoms, such as a return of depression and anxiety, mood swings, dizziness, trouble sleeping, flu-like symptoms, and digestive issues. Do not stop taking the medication without discussing the risks and the benefits with your doctor first. Your healthcare provider can tell you how to lower the dose slowly.

Which Is Safer: Zoloft or Prozac?

Studies show that Zoloft is likely to cause fewer and less severe side effects. However, Zoloft and Prozac can both cause serious side effects such as rash, hives, swelling, difficulty breathing, confusion, memory problems, agitation, hallucinations, sweating, and fast heartbeat. Call your doctor or healthcare provider immediately if you experience any of these adverse effects while on SSRI treatment.

Weight Gain on Prozac Vs Zoloft

Both Zoloft and Prozac may lead to weight changes, including weight loss and weight gain. A 2016 study suggested that people gain slightly more weight on Zoloft compared to Prozac (10.5 lbs vs 4.6 lbs over a two-year period). However, a meta-analysis of peer-reviewed studies indicated that both Prozac & Zoloft as well as other SSRI medications can cause weight gain.

Is Zoloft Sedating or Energizing?

Zoloft and other antidepressants can be both sedating and energizing. Sleepiness and fatigue are common side effects of these drugs, so they can be sedating. However, low energy is a common symptom of major depression, and by treating depression, Zoloft and other antidepressants can have an energizing effect. You should start to feel less tired and sleepy and more energetic once your body adjusts to the antidepressant drug, the side effects abate, and the full effects of the drug kick in.

Note: While SSRIs do not have a direct severe interaction with alcohol, it’s a good idea to limit your alcohol intake while on antidepressant drugs because of the increased risk of excessive drowsiness as a side effect when alcohol and antidepressants are taken together. 

Dosage and Administration

Standard Dosages for Prozac and Zoloft

The starting dose of Prozac in adults with major depressive disorder or obsessive-compulsive disorder is 20 mg once daily in the morning. 

The starting dose of Zoloft in adults with major depressive disorder, obsessive-compulsive disorder, and premenstrual dysphoric disorder is 50 mg once daily. The initial dose of Zoloft for adults with panic disorder, PTSD, and social anxiety disorder is 25 mg once daily.

Dosage Adjustments and Titration

The dose of Prozac can be increased from 20 mg once daily to 20 mg twice daily (morning and noon) if needed. The usual maintenance dose of Prozac is between 20 mg and 60 mg per day. The maximum dose of Prozac is 80 mg per day.

The therapeutic maintenance dose range of Zoloft is between 50 mg and 200 mg per day.

Interactions with Other Medications

Both Zoloft and Prozac have similar drug interactions. They can interact with prescription and over-the-counter drugs such as monoamine oxidase inhibitors (MAOIs), pimozide, and St John’s Wort, among others. 

MAOIs and St. John’s Wort are also used to treat depression. This type of drug interaction can cause a serious, potentially life-threatening condition called serotonin syndrome due to too much serotonin in your body. Signs and symptoms of serotonin syndrome may include agitation, fever, excessive sweating, tremors, confusion, rapid heart rate, and major fluctuation in blood pressure. You should seek emergency medical care if you experience any of these symptoms. 

Final Considerations and Conclusion

Personalize Treatment Choices

It is best to work with your healthcare provider to determine which antidepressant medicine may be best for you, between Prozac & Zoloft. Your doctor will perform a comprehensive examination and decide on the best treatment based on your symptoms, coexisting medical conditions, and personal preferences. 

Consult Healthcare Providers

If you have treatment-resistant depression that does not respond to Prozac or Zoloft, your healthcare provider may advise giving Zoloft / Prozac more time, increasing your dose, or switching you to a different type of antidepressant.

Manage Expectations and Keep Followup Appointments

Antidepressants such as Prozac and Zoloft do not start working immediately. It can take 4-6 weeks to get the full benefits of these medications. Continue taking the medicine even if you don’t notice an immediate improvement in your symptoms. Keep all your healthcare appointments while on an antidepressant. Tell your doctor how you are feeling so they can adjust your treatment accordingly.