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The Controversial History of Fluoxetine, Prozac’s Active Ingredient

Last Updated on January 29, 2026 by Carol Gillette

Alternative to Meds Editorial Team
Medically Reviewed by Dr Samuel Lee MD

When people are dealing with mental health problems like depression or anxiety, Prozac has become one of the most prescribed solutions. Prozac’s approved uses include major depressive disorder, OCD, bulimia, and panic disorders. Prozac/fluoxetine is approved for acute depression in bipolar conditions and for “treatment resistive depression” if prescribed along with olanzapine, an antipsychotic medication. Treatment resistive depression means 2 or more other antidepressants have been tried and found unsuccessful.1 Marketing Prozac encourages a person to take the medication and become a joyous, productive member of society. All too often, however, with Prozac, that scenario proves to be far from reality. Learn more about what, exactly, does the active ingredient in Prozac (fluoxetine hydrochloride) do, and how it came to be so controversial in today’s world?

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Empowerment Increases through Learning the Facts about Medical Issues

When faced with a confusing or concerning medical issue, we often rely upon the knowledge and expertise of medical professionals when it comes to treatment options, trusting that they are making the choice that is in our best interests. However, that also means neglecting personal due diligence when it comes to researching medication. Worse, many of us fail to explore any alternative solutions. As it turns out, there’s more to learn about many of the drugs on the market today that even prescribers may not be aware of.

While fluoxetine is classed as an antidepressant, it is more specifically an SSRI, or selective serotonin reuptake inhibitor. The aim of SSRIs is to help increase the level of serotonin active in the brain. Serotonin is a natural chemical — a neurotransmitter — that buffers the impact of outside stimulation, and naturally plays a significant role in mood, promoting feelings of relaxation and ease. Serotonin also regulates thousands of other functions of the body, including digestion, sleep, blood sugar levels, metabolism, growth, gastrointestinal motility, and a very wide range of other vital functions.6

Like all other hormones, if too much or too little is available, a person can experience a significant impact. In fact, serotonin dysregulation can cause serious issues. No drug can create serotonin. Serotonin (and many other natural chemicals) are produced mainly in the gut, and distributed along the body’s highly refined system of nerve channels. Drugs like fluoxetine can manipulate the transmission of serotonin, but cannot create more.7

In addition,  the idea of specifically targeting serotonin in the treatment of depression has been under robust debate as the mechanics may be more nuanced than was previously believed. 2-4

How Do Issues With Serotonin Production Affect the Human Body?

Interest in serotonin seems to have two categories: issues that arise when there’s a scarcity of serotonin and issues that occur when there’s too much serotonin. The former is the narrative often cited as a contributor to anxiety and depression, although the evidence for that has become seriously in question. Prozac was originally marketed to correct a “serotonin imbalance.” The theory was that Prozac could correct an imbalance of serotonin and relieve feelings of unhappiness, hopelessness, and even suicidal ideation.

Ironically, fluoxetine carries a black box warning for suicide.12 The theories supporting prescribing fluoxetine to correct a serotonin imbalance have been questioned by researchers such as Moncrief, Horowitz, and many others, although the marketing campaigns still cling to it.2-4

More on the marketing of fluoxetine can be found below.

What is Serotonin Syndrome?

serotonin issuesElevated levels of serotonin can be problematic. Instances where there is too much serotonin activated may lead to serotonin syndrome. This is a state of toxicity where medication has caused too much serotonin has been expressed. Some cases of SS occur after a single dose of a serotonergic medication, and other cases occur where 2 or more serotonergic agents have been taken concurrently. For example, St. John’s Wort should not be taken concurrently with an SSRI medication, due to their combined effects.

The condition is potentially life threatening and needs immediate treatment to save the patient’s life. It’s one of the rare scenarios where abrupt cessation of the drug is necessary. Since serotonin regulates so many systems in the body, many negative presentations can arise with serotonin toxicity. Some of the clinical abnormalities that are signs and symptoms of serotonin syndrome are listed below. Doctors should not only be aware of these symptoms, but should inform their patients before prescribing SSRIs like Prozac.

Signs and symptoms of serotonin syndrome:
  • Elevated heart rate (tachycardia)
  • Unstable heart rate
  • Seizures
  • Increased or unstable blood pressure
  • Hyperthermia (overheating due to loss of internal regulation)
  • Profuse sweating (diaphoresis)
  • Confusion
  • Agitation
  • Dilated pupils
  • Akathisia
  • Tremors (rhythmic involuntary muscle movements)
  • Sudden, brief, involuntary jerky muscle spasms (myoclonus)
  • Increased or overactive reflex responses (hyperreflexia)
  • Coma, unresponsiveness
  • Muscle rigidity
  • Flushed skin
  • Sweating
  • Increased bowel activity

If these sign present, one should seek immediate medical attention. Call 911 or have someone arrange transport to the nearest ER unit without delay. Early recognition and treatment, such as giving the patient a serotonin agonist before complete shutdown occurs, are vital for the patient to survive.5,15

What Does an SSRI Do?

SSRIs are compounds that specifically target serotonin molecules. Serotonin is a natural neurotransmitter, a messenger molecule. The messenger’s job is to carry signals throughout the central nervous system, telling other cells what to do, or what not to do. SSRIs block this pathway, so the messenger molecules become suspended, instead of continuing to travel along their normal relay line, on to the next receptor in the the nerve pathway. Chronic use of SSRIs can trigger what is called downregulation. Downregulation of serotonin receptors occurs over time, which means they become less responsive, and less in number.10

You might think of the central nervous system as a giant switchboard consisting of lines, receivers, transmitters, and of course, messages. Neurotransmitters such as serotonin have the task of sending communication between various parts of your body, transmitting signals between neurons to other cells. After delivering the message, the serotonin molecules are normally reabsorbed into the vesicles (storage sacs) of the nerve cells in your body. There they remain protected, ready to be used again, and again, as the need arises.

However, an SSRI disables this process. The serotonin molecules can’t be stored in the vesicles, and they remain suspended, and now subject to deterioration via nearby enzymes. So over time, these serotonin molecules can deteriorate and become waste material. Whether or not one had a serious serotonin deficiency before antidepressant use, after SSRI use this is certainly a possibility. Animal studies have shown this to be true.8,9

The History of Fluoxetine

ground-up rat brains used in development of fluoxetine prozacWe have a lot of rats to thank for the development of fluoxetine, according to the American-based Institute of Science History.10 Chemists employed by Eli Lily borrowed a method introduced to them by a John’s Hopkins chemist named Solomon Snyder. Snyder showed them how he first drugged rats with chlorpromazine, an antipsychotic, ground up their brains, and took extracts of those rat brains. Snyder found that these rat-brain-extracts responded to other experiments just the same way live nerve endings responded.

So, many chemists at Eli Lily experimented with drugging rats with other chemicals, grinding up their brains, and using the rat-brain-extracts as Snyder had showed them. They found one compound in particular had the effect of stopping serotonin reuptake in ground-up-rat-brains.

That was the birth of fluoxetine.10

The other part of the story was the narrative about natural transmitter deficiencies leading to depression, and the idea that Prozac and other SSRIs could correct such a deficiency. Since 1987, this theory has come under scrutiny.2-4

The Marketing of Prozac

The efforts dedicated to marketing Prozac cannot be understated. Prior to Prozac’s release, antidepressants in general and ECT as another treatment for depression, had become unpopular mainly due to their dangerous side effects. Prozac was touted as the super-drug that was going to change all that.

the marketing of prozacEverything from the promotional language surrounding its release to the materials given to medical professionals to the very name of the drug was intentionally chosen to maximize its positive reception. The name Prozac was developed to appear both professional and snappy, remaining in line with the overall messaging of fluoxetine serving as a “one-pill-fits-all” solution.

The main angle of the promotional materials advertising Prozac used the guise of teaching vital information about depression to consumers, cautioning the public about the dangers of remaining depressed while extolling the benefits of Prozac. This came at a time where previous negative experiences with the side effects of antidepressants weighed heavily upon the populace, making the promise of an exciting, effective new drug even more enticing. Prozac became a trendy choice, recommended by celebrities, best-selling books like “Prozac Nation,” and “Listening to Prozac”, and the name “Prozac” saturated all media.

In addition to targeting those with depression, Prozac was promoted towards increasingly larger groups of people to continue capitalizing on the drug’s popularity. Not only was it recommended to those with diagnosed depression and anxiety, but it was also offered as a potential cure for those who simply struggled with shyness or those looking for an easy way to feel happier. Over time Prozac was even marketed towards children. In fact, the FDA approved it for children age 7 with OCD, and age 8 for children diagnosed with MDD (major depressive disorder.)11,12

Controversy Over Fluoxetine

The biggest challenge fluoxetine faces is the truth about its effectiveness. A marketing formula was heavily promoted: low serotonin equals depression, so a drug that helps you increase serotonin should cure it. Even a child could understand the concept. What could possibly be missing in this equation? In fact, the conversation about the hype surrounding Prozac is often missing facts about side effects, efficacy, managing Prozac withdrawal safely, as well as nuance and individual contexts of the persons who are prescribed such a drug.

It’s true that there is a relationship between neurochemicals and the functions of the body. However, like the other hormones and neurotransmitters in your system, serotonin does not work in isolation. There are many distinct factors that could potentially have an impact on the various facets of your health, including depression. Under certain circumstances, our emotional state and stress levels can actually affect our brain chemistry. This begs important questions. Are reduced serotonin levels more of a symptom of depression than the source? Is there a causative and direct relationship at all?

New research begins to peel away some of the blurred lines. There has been no actual evidence that low serotonin is the main cause of depression, or any of the other conditions Prozac is used to treat like obsessive-compulsive disorders, eating disorders, and many others off-label. In fact, in 2003/4, JAMA released statements as did the National Health Service in the UK denouncing the use of Prozac and 6 other “newer” antidepressants in those under the age of 18. Lack of efficacy and harmful risks were the reasons for the ban. In 2021, Eli Lily revised their prescriber information to include 10 pages of warnings that were not in the original prescribing guidelines.13,14

So the light is beginning to shine.

Risks of Prozac

prozac fluoxetine increased serotonin levelsIn addition to questions about its value as an antidepressant, Prozac also presents some significant risks. First, common negative side effects include nausea, increased anxiety, trouble sleeping, and fatigue. Some patients also report significant side effects like agitation, akathisia, rage, hostility, and other extreme changes to their mood. Also reported are uncontrollable muscle spasms, tremors, decreased libido, and sexual dysfunction even after withdrawal from the drug. One of the most serious possible side effects is increased thoughts of suicide.

As mentioned above, there is also a heightened chance of developing serotonin syndrome while taking Prozac, or any of the SSRI medications. Serotonin syndrome occurs most frequently when a dose is changed, when a second serotonergic medication is added, in overdose, or when serotonergic medications are switched. Because SSRI drugs interfere with the natural serotonin uptake process, it’s possible for you to end up with too much serotonin being activated. Increased serotonin levels subject you to many negative symptoms, on top of Prozac’s side effects, and the initial condition that prompted your doctor to prescribe Prozac in the first place.

Finally, there is the matter of withdrawal. Prozac’s metabolite has a very long half-life, meaning it stays active in the body for between 4 and 16 days. Nonetheless, persons being withdrawn from Prozac are advised to do so gradually to avoid unnecessary discomfort. And prescribers are particularly cautioned not to prescribe other medications, especially those in the SSRI class, before complete blood plasma elimination, due to the risk of severe drug-drug interactions. Symptoms of withdrawal syndrome include digestive issues like nausea and vomiting, dizziness, flu-like symptoms, worsened depression, worsened sleep, and many others. Seek trusted help and; guidance for withdrawal from mental health drugs for the safest outcome.

Prozac, Zoloft, and Luvox, Other SSRIs

SSRIs do your due diligenceOften, the names of Prozac, Zoloft, Luvox, and other drugs are easily confused, as they are all classified as SSRI antidepressants. In fact, in everyday conversations surrounding medication meant to treat common mental health issues like anxiety and depression, these three are used so interchangeably it might make a person wonder, what is Luvox (fluvoxamine)? Is Luvox the same as Prozac? Is there a difference between Prozac and Zoloft, or other SSRIs?

In fact, each of these drugs has a slightly different active ingredient. As we know, Prozac depends on the active ingredient fluoxetine. Meanwhile, Zoloft has the active ingredient sertraline, and Luvox has the active ingredient fluvoxamine. All these ingredients have the same basic purpose, but they affect the body in diverse ways. For example, Prozac has different withdrawal symptoms than Zoloft, Luvox side effects differ from Prozac’s, and Zoloft uses differ a bit as compared to Luvox uses. That’s why it’s important to apply the same level of critical thinking to every drug, regardless of how similar they might seem to others. Although Prozac, Zoloft and Luvox are all SSRIs, the smallest of differences could lead to a significant impact on a person’s health.

First, one is encourage to do one’s own due diligence in selecting treatment for depression, anxiety or other unwanted symptoms. That will be a good starting point for a discussion with a trusted healthcare provider.

The Truth About Prozac

Some people have reported success with Prozac and other SSRIs. And Prozac has some therapeutic use as a bridge medication where other drugs with a shorter half-life may be too difficult to endure in withdrawal. However, many people have reported significant side effects and failures as well. Unfortunately, the way the media and the medical community frame information about Prozac is often skewed towards the positive, despite what the research indicates. That’s why it’s extremely important to be a strong advocate for one’s own health, starting by becoming as well informed as possible about any new medications. Where possible, learn background information to discuss with your prescriber, and learn more about all available options prior to introducing a new substance into the body.

Knowledge is a vital tool that could prevent unnecessary harm. And, knowledge can significantly impact your quality of life for the better. Additional recommended reading:

Sources:


1. NIMH Binge Eating Disorder [archived] last reviewed 2010 [cited 2025 Nov 12]

2. Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2023 Aug;28(8):3243-3256. doi: 10.1038/s41380-022-01661-0. Epub 2022 Jul 20. PMID: 35854107; PMCID: PMC10618090.[cited 2025 Nov 12]

3. Hillhouse TM, Porter JH. A brief history of the development of antidepressant drugs: from monoamines to glutamate. Exp Clin Psychopharmacol. 2015 Feb;23(1):1-21. doi: 10.1037/a0038550. PMID: 25643025; PMCID: PMC4428540.[cited 2025 Nov 12]

4. Salomon RM, Miller HL, Krystal JH, Heninger GR, Charney DS. Lack of behavioral effects of monoamine depletion in healthy subjects. Biol Psychiatry. 1997 Jan 1;41(1):58-64. doi: 10.1016/0006-3223(95)00670-2. PMID: 8988796.[cited 2025 Nov 12]

5.  Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions. Int J Tryptophan Res. 2019 Sep 9;12:1178646919873925. doi: 10.1177/1178646919873925. PMID: 31523132; PMCID: PMC6734608..[cited 2025 Nov 12]

6. Jones LA, Sun EW, Martin AM, Keating DJ. The ever-changing roles of serotonin. Int J Biochem Cell Biol. 2020 Aug;125:105776. doi: 10.1016/j.biocel.2020.105776. Epub 2020 May 29. PMID: 32479926.[cited 2025 Nov 12]

7. Chen Y, Xu J, Chen Y. Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients. 2021 Jun 19;13(6):2099. doi: 10.3390/nu13062099. PMID: 34205336; PMCID: PMC8234057.[cited 2025 Nov 12]

8. Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554406/ [cited 2025 Nov 12]

9. Siesser WB, Sachs BD, Ramsey AJ, Sotnikova TD, Beaulieu JM, Zhang X, Caron MG, Gainetdinov RR. Chronic SSRI treatment exacerbates serotonin deficiency in humanized Tph2 mutant mice. ACS Chem Neurosci. 2013 Jan 16;4(1):84-8. doi: 10.1021/cn300127h. Epub 2012 Oct 1. PMID: 23336047; PMCID: PMC3547473. [cited 2025 Nov 12]

10. Science History Institute Biographies Fuller, Wong, Molloy published ND [cited 2025 Nov 12]

11. Das A, Pharmaceutical industry and the market: The case of Prozac and other antidepressants, Asian Journal of Psychiatry, Volume 4, Issue 1, 2011, Pages 14-18, ISSN 1876-2018, [cited 2025 Nov 12]

12. FDA drug label Prozac (fluoxetine hydrochloride) first approval 1987 [cited 2025 Nov 12]

13. Eli Lily Patient & Prescriber Information Prozac (fluoxetine hydrochloride) oral capsules, Antidepressant, Antiobsessional, Antibulimic, published 1989, revised 2021 [cited 2025 Nov 13]

14. Kondro W. UK bans, Health Canada warns about antidepressants. CMAJ. 2004 Jul 6;171(1):23. doi: 10.1503/cmaj.1040981. PMID: 15238484; PMCID: PMC437670. [cited 2025 Nov 13]

15. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore). 2000 Jul;79(4):201-9. doi: 10.1097/00005792-200007000-00001. PMID: 10941349. [cited 2025 Nov 14]

16.  Prozac: FDA approved  Medication Guide for Patients published online 2009 Eli Lily &  co. [cited 2026 Jan 29]


Originally Published November 14, 2025 by Diane Ridaeus


This content has been reviewed and approved by a licensed physician.

Dr. Samuel Lee

Dr. Samuel Lee is a board-certified psychiatrist, specializing in a spiritually-based mental health discipline and integrative approaches. He graduated with an MD at Loma Linda University School of Medicine and did a residency in psychiatry at Cedars-Sinai Medical Center and University of Washington School of Medicine in Seattle. He has also been an inpatient adult psychiatrist at Kaweah Delta Mental Health Hospital and the primary attending geriatric psychiatrist at the Auerbach Inpatient Psychiatric Jewish Home Hospital. In addition, he served as the general adult outpatient psychiatrist at Kaiser Permanente.  He is board-certified in psychiatry and neurology and has a B.A. Magna Cum Laude in Religion from Pacific Union College. His specialty is in natural healing techniques that promote the body’s innate ability to heal itself.

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