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Key Takeaways
- Prozac and Zoloft are similar selective serotonin reuptake inhibitors (SSRIs) prescribed for anxiety and depression.
- Prozac is FDA-approved for depression or bulimia, while Zoloft is FDA-approved for treating PTSD and social anxiety.
- Both drugs share similar side effects and safety profiles, including the risk of serotonin syndrome.
Prozac (fluoxetine) and Zoloft (sertraline) are both selective serotonin reuptake inhibitors (SSRIs), and both treat some mental health conditions, including depression and anxiety. They’re similar, but there can be key differences in approved uses, side effects, and effectiveness for other conditions. One may work better than the other, depending on the person.
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What’s Similar About Prozac and Zoloft?
Prozac and Zoloft are both selective serotonin reuptake inhibitors (SSRIs). They disrupt the function of serotonin, a neurotransmitter (chemical messenger) in the brain. More serotonin is available for chemical messaging when SSRIs prevent serotonin reuptake and storage, but genetics and other factors also are in play. Research continues into how SSRIs work.
The Food and Drug Administration (FDA) approved Prozac and Zoloft to help manage:
Common side effects seen in both medications include nausea, diarrhea, and trouble sleeping.
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—a potentially life-threatening drug reaction.
How Do SSRIs Work?
SSRIs help treat depression and anxiety by changing how the chemical messenger serotonin works in your brain. Serotonin is a chemical stored and released to provide feel-good signals in the brain. It’s not entirely clear how SSRIs work, but making serotonin available can boost mood over time as the neurotransmitter carries signals between neurons.
Different Uses for Zoloft vs. Prozac
The main differences between Prozac and Zoloft are based on what mental health conditions they can help manage.
In addition to their shared uses, Prozac is FDA-approved to help with:
- Bulimia nervosa (BN)
- Treatment-resistant depression
- Depression and bipolar in combination with Zyprexa (olanzapine)
Unlike Prozac, Zoloft is FDA-approved for:
- Post-traumatic stress disorder (PTSD)
- Social anxiety disorder (SAD)
- Premenstrual dysphoric disorder (PMDD)
Prozac and Zoloft are available to be taken once a day. A once-weekly fluoxetine option exists to maintain a maintenance level after treatment response to daily fluoxetine. It’s not typically used to treat active symptoms.
While it usually takes a few weeks for Zoloft or Prozac to start working, Zoloft seems to work more quickly. However, it may take a month or two before you feel the full effects.
Off-Label Uses of SSRI Drugs
Both Zoloft and Prozac can be used to treat body dysmorphic disorder (BDD), which shares some features of OCD. The SSRIs are not FDA-approved for this use but they remain a first-line choice for those living with BDD and a distorted view of their appearance. Other off-label SSRI uses include:
- Irritable bowel syndrome
- Menopause symptoms
- Premature ejaculation
The drugs may be used in place of each other; i.e., Prozac also is used to treat PTSD. More study is needed on potential SSRI therapies.
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 three-month study involving 500 people suggested that Prozac, Zoloft, and Paxil (paroxetine) worked the same in helping to reduce depression.
- Generalized anxiety disorder: A research review involving more than 13,000 participants evaluated the effectiveness of several SSRIs for treating generalized anxiety disorder. The study concluded that Prozac was more effective, but those who took Zoloft experienced fewer side effects.
- Obsessive-compulsive disorder: A research review concluded that SSRIs, including Prozac and Zoloft, provide similar effectiveness in treating OCD. In addition, the combination of going to therapy and taking medications provides the most benefit for managing OCD. Higher doses may help some people with OCD but can be risky.
- Panic disorder: Both Prozac and Zoloft are effective in treating panic attacks. Some studies suggest Prozac may be more effective.
Zoloft vs. Prozac Dosing
Zoloft and Prozac are available in different forms and different strengths.
| Dosage Guidelines for Adults | ||
|---|---|---|
| Prozac | Zoloft | |
| Generic name | fluoxetine | sertraline |
| Forms | capsule | tablets, oral solution |
| Strengths | 10 mg, 20 mg, 40 mg | 25 mg, 50 mg, 100 mg (tablets) 20 mg per mL in 60 mL bottle with 25 mg and 50 mg dropper (oral solution) |
| Therapeutic dosage range (adults) | 20-60 mg (max 80 mg) | 50-200 mg |
| Suggested starting dose | MDD: 20 mg/day OCD: 20 mg/day Bulimia: 60 mg/day Panic disorder: 10 mg/day |
MDD: 50 mg/day OCD: 50 mg/day PTSD: 25 mg/day PMDD: 50 mg/day |
Prozac is also used in combination with a medication called Zyprexa (olanzapine) to treat certain conditions, including:
- Depressive episodes associated with bipolar I disorder: 5 mg of oral olanzapine and 20mg of fluoxetine (suggested starting dose).
- Treatment-resistant depression: 5 mg of oral olanzapine and 20 mg of fluoxetine (suggested starting dose).
Keep in mind that dosage recommendations for children, older adults, and people with other medical conditions may vary. It is important to work closely with your healthcare provider to get the best treatment.
SSRIs and Pregnancy
While studies suggest that SSRIs do not significantly increase the risk of birth defects during pregnancy, the American College of Obstetricians and Gynecologists recommends discussing the use of any antidepressant with your provider. Also, it is important to note that the oral solution of Zoloft is not recommended during pregnancy because it contains 12% alcohol.
Common Side Effects
Some common side effects that both Prozac and Zoloft share include:
- Nausea
- Diarrhea
- Dizziness and weakness
- Headache
- Trouble sleeping
The drugs work in the same way, so other side effects seen with Prozac and Zoloft include:
- Strange dreams
- Nervousness
- Yawning
- Nose or throat irritation
- Dry mouth
- Increased sweating
Prozac stays in the body longer than Zoloft. Its use generally has a lower risk of symptoms when you stop taking the drug. It also requires more time between stopping Prozac and starting a new drug.
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 also seen in Prozac and Zoloft include:
- Feeling anxious or experiencing panic attacks
- Trouble controlling body movements
- Throwing up or coughing blood, though this is quite rare
- Severe skin reactions such as blisters, peeling skin, red eyes, or sores in the mouth
FDA Black Box Warning on SSRI Use
In 2004, the Food and Drug Administration issued a high-level black box warning for SSRI use in children, adolescents, and young adults due to the risk of suicidal thoughts and behaviors. The FDA warning remains in place. Data suggest a small increase in suicidal thoughts and behaviors in individuals under 25, particularly early in treatment. Careful monitoring is recommended.
Potential Drug Interactions
Since Prozac and Zoloft are both SSRIs, they have similar drug interactions.
Serotonin Syndrome
Avoid taking the following products 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. This potentially life-threatening condition is characterized by too much serotonin in the body and can lead to seizures, high fever, or hallucinations.
Examples of common antidepressants include:
- Nardil (phenelzine)
- Amitriptyline
- Lexapro (escitalopram)
- Cymbalta (duloxetine)
Bleeding
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)
Abnormal Heart Rhythms
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)
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.
The author would like to recognize and thank Alexya Rosas for contributing to this article.