Comparison of Fluoxetine (Prozac) vs. Sertraline (Zoloft)
When considering your mental health treatment options, a common choice is Sertraline (sertraline hydrochloride), known by the brand name Zoloft. Another is Fluoxetine, known by the brand name Prozac.
Both are SSRI (selective serotonin reuptake inhibitors) medications. They work by inhibiting reuptake, making the neurotransmitter serotonin more available. Healthcare providers prescribe them for several mental health conditions, including major depression.
At Levelheaded Mind, we want you to be informed about your healthcare choices. Through education, you can work with your healthcare provider to make the best decisions for your mental health. Therefore, in this article, you will find:
The conditions treated by Fluoxetine (Prozac) and Sertraline (Zoloft)
How the medications work
Side effects
Drug interactions
How each medication is taken
Helpful resources
The Conditions Treated by Fluoxetine (Prozac) and Sertraline (Zoloft)
Both Fluoxetine (Prozac) and Sertraline (Zoloft) are approved by the Food and Drug Administration (FDA) to treat:
Premenstrual Dysphoric Disorder (PMDD)
Panic Disorder
Obsessive Compulsive Disorder (OCD)
While both are used to treat these conditions, there are different age restrictions.
Fluoxetine (Prozac) is one of two antidepressant medications that is FDA-approved to treat Major Depressive Disorder (MDD) for children and adolescents ages eight and older. It is also FDA-approved to treat Obsessive Compulsive Disorder (OCD) for children and adolescents ages seven and older.
Sertraline (Zoloft) is FDA-approved to treat Major Depressive Disorder (MDD) for adults only, including young adults. It has FDA approval to treat Obsessive Compulsive Disorder (OCD) for children and adolescents ages six and older.
Fluoxetine (Prozac) is an FDA-approved treatment option for
the eating disorder bulimia nervosa (particularly in high doses)
bipolar disorder (Fluoxetine (Prozac) may be combined with Olanzapine)
treatment-resistant depression (Fluoxetine (Prozac) may be combined with Olanzapine)
Sertraline (Zoloft) is an FDA-approved treatment option for
Post Traumatic Stress Disorder (PTSD)
Social Anxiety Disorder
However, your healthcare provider may prescribe either of these medications off-label to treat conditions they are not FDA-approved to treat.
How the Medications Work
Fluoxetine (Prozac) enhances the release of norepinephrine and dopamine, which is generally activating. The result is improved concentration, attention, and energy. This action also contributes to an anti-bulimia effect, particularly in higher doses.
Fluoxetine Activating Effects
This activating effect makes Fluoxetine (Prozac) a strong treatment option when you have symptoms such as a flat affect, fatigue, overeating, or sleeping too much.
When combined with Olanzapine, the effects are further enhanced, making it a superior treatment option for treatment-resistant depression and bipolar disorder, a type of affective disorder.
However, for some patients, the activating effects may be too much. This is particularly true for patients with anxiety. In this case, Fluoxetine (Prozac) would need to start at a low dose. The lowest available dose is 10 mg. Then, you may work slowly up to a therapeutic dose, which is between 20 mg - 60 mg.
Sertraline (Zoloft) acts as a weak dopamine transport inhibitor (DAT), which improves energy, motivation, and concentration. When combined with Bupropion, this effect is exaggerated, making this a popular combination.
Sertraline Anti-Anxiety Effects
Sertraline (Zoloft) has been shown to have an anti-anxiety effect. The exact nature of how this takes place is not fully understood but has been shown to be a benefit. It is also effective in treating psychotic depression.
This means that Sertraline (Zoloft) is effective in treating atypical depression due to the effects of improved concentration, attention, and energy. It is also a superior choice when treating symptoms of depression mixed with anxiety. Furthermore, it is effective in treating PTSD and treating patients who have experienced trauma but may not have the symptomology of PTSD.
Side Effects
There are similar side effects with both medications. Both have black box warnings outlining an increased risk of rare and dangerous side effects. These may include a risk of suicidal thoughts. There may also be a serotonin syndrome risk when serotonin levels build up in the body. It is important to be aware of these potentially serious side effects. Contact your healthcare provider immediately if you experience any of these symptoms.
More common side effects that may be caused by both medications are:
Gastrointestinal (GI) upset in the first week of taking the medication
Effects on blood pressure
Drowsiness
Dry mouth
Weight gain or weight loss
Additionally, one of the side effects of Zoloft is the tendency to have more reports of sexual dysfunction than Prozac.
The side effects of Prozac are headache and nervousness.
It is wise to keep your healthcare provider informed of any adverse effects you are experiencing. You are at an increased risk of adverse effects if you drink alcohol while taking these medications.
Drug interactions
When considering drug interaction, it is important to inform your healthcare provider of all medications and supplements you are taking. Both Fluoxetine (Prozac) and Sertraline (Zoloft) inhibit particular enzymes which are involved in the metabolism of drugs in the body. Sertraline (Zoloft) is a weaker inhibitor of the two medications.
Fluoxetine (Prozac) will have more drug interactions
Since Fluoxetine (Prozac) is the stronger inhibitor of the two medications, it will have more drug interactions. If you are taking several medications, it is more likely Fluoxetine will have a drug interaction. This will require discussing with your healthcare provider the possibility of altering dosage or alternative medications.
Of the two medications, Fluoxetine has a longer half-life, so before starting another medication, be aware that metabolites may still be in your system for five weeks or more. This is another time to watch for drug interactions.
Fluoxetine (Prozac) has less chance of withdrawal symptoms
The advantage of this long half-life is that it lessens the effect of abstinence syndrome. Therefore, it is more likely you can stop taking Fluoxetine (Prozac) safely with minimal or no withdrawal symptoms. As with all prescription medications, consult your healthcare provider before discontinuing use.
How Each Medication is Taken
Both are taken orally, once daily. They are usually taken in the morning with or without food.
Sertraline (Zoloft) comes in tablet form and oral solution. The advantage of tablets is that they can be divided if dosing changes become necessary.
Fluoxetine (Prozac) comes in capsule form and oral solution. Fluoxetine (Prozac) is also available in a weekly dosing capsule.
Helpful Resources for Your Next Steps
With this knowledge, you can have informed discussions when seeking medical advice from your healthcare providers, pharmacist (pharm.d), and mental health professionals.
Both Fluoxetine (Prozac) and Sertraline (Zoloft) can be effective treatments for your mental health conditions, helping with your well-being. Understanding the specific uses, side effects, and drug interactions allows you to evaluate which medication is right for you.
At Levelheaded Mind, Jezel Rosa, PMHNP-BC, is available to discuss your mediation choices and help you explore whether Fluoxetine (Prozac) or Sertraline (Zoloft) is your best treatment option. You can speak directly by scheduling a coaching/consultation session with Jezel Rosa, PMHNP-BC.
For more information about Fluoxetine (Prozac) and Sertraline (Zoloft), watch Comparison of Fluoxetine (Prozac) vs. Sertraline (Zoloft) on YouTube.
Disclaimer: All the information on this website is for educational purposes and not intended to be specific/personal medical advice or substitute for diagnosis and treatment of any conditions discussed herein. Furthermore, reading our blogs, watching our videos, or getting answers to comments/questions does not establish a provider-patient relationship. Please consult with your own healthcare provider for proper diagnosis and treatment.
References
Medical News Today (2019). What are the differences between Prozac and Zoloft. Retrieved from https://www.medicalnewstoday.com/articles/325684#side-effects
Stahl, S. M., Grady, M. M., & Muntner, N. (2021). Stahl's essential psychopharmacology: Neuroscientific basis and practical applications. Cambridge University Press.
Stahl, S. (2017). Stahl's Essential Psychopharmacology: Prescriber's Guide, 6th Ed. Cambridge University Press. https://amzn.to/3Vui1II
Food and Drug Administration (FDA) www.fda.gov
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