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Your Guide to the Long-term Effects of Prozac

Last Updated on November 21, 2022 by Carol Gillette

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

Prozac has often been called the miracle SSRI that revolutionized the treatment of depression. Sales were astounding! The graph of antidepressant sales resembles the trajectory of a 747 taking off to heights never before seen. However, the graph of rising mental health disabilities looks identical.

However, in 2005, the FDA required a black box warning on all SSRIs for increased suicidality. And, in 2005, the 747-style trajectory of both graphs begins a sudden dramatic descent showing that fewer prescriptions were written, and fewer deaths by suicide also occurred.1-3 Clearly, drug therapy is not the answer that we were led to believe, or that we were hoping for.

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What is Prozac?

what is prozacProzac (generic fluoxetine} is an SSRI drug. It comes in immediate and enteric-coated (extended-release) versions. It is FDA-approved to treat MDD (major depressive disorder), bulimia (eating disorder), panic disorder, and OCD (obsessive-compulsive disorder).4  A product called “Sarafem©” was brought to market for menstrual-related issues.25  It is the same drug, fluoxetine, targeting women specifically. But Sarafem carries the same black box warnings and other potential risks as any other fluoxetine product. The theory behind treatment with SSRI drugs is that these drugs immobilize the serotonin transporter system, allowing for an accumulation or concentration of serotonin at the nerve synapses. That the SSRI had an activating effect on depression symptoms was reason to believe that a deficiency of these chemicals was present. This now virtually debunked “chemical imbalance theory” has supplanted most other therapies for many decades. Earlier drugs attempted to do much the same with other chemicals — creating something of a chemical domino effect — to alter the distribution of certain natural hormones like serotonin and others, to attain improvements in mental health.5 The purpose sounds good, in theory at least, which is to chemically change behavior and mood.

There are problems with this theory that have come to light, especially after the long-term effects of Prozac have been more thoroughly studied. According to Moncrieff et al in a published decades-long body of SSRI and antidepressant research, the authors suggest that while antidepressants do have mind-altering effects, and have an emotion-numbing characteristic, they should not be regarded as clinically therapeutic above the level of a placebo.6,7

Common and Rare Long-term Effects of Prozac

SSRIs are typically prescribed long-term for months and years. The most commonly reported adverse effects of Prozac therapy come from short-term studies. Prozac has an activating effect that typically manifests within the first few weeks. These initial newly emerging effects can be immediate. Some examples include suicidal thoughts and behavior, rashes, panic attacks, anxiety, agitation, insomnia, mood fluctuations, and some paradoxical reactions, which are sometimes misdiagnosed as Bipolar.8 However, the long-term effects of Prozac linger well beyond the first few days or weeks of treatment. A list below shows examples, followed by a more expanded description.

prozac long term effectsLong-term effects of Prozac can include:
  • Lengthened half-life elimination due to liver toxicity
  • Growth attenuation
  • Sexual dysfunction
  • Changes to weight
  • Risks in pregnancy
  • Impaired quality of life
  • Tolerance, original symptoms re-emerge

Lengthened half-life elimination:  Drug-induced liver damage can occur as soon as 2 to 12 weeks of treatment, or over a longer period. Liver toxicity lengthens the elimination window. Prozac already has the longest half-life of all SSRIs currently on the market. Hepatitis and acute liver failure are possible outcomes without intervention. While positively identified, the mechanism by which Prozac causes liver damage is unknown.9

Growth attenuation:  While the exact mechanism has not been established, retardation of growth is associated with long-term Prozac use, as well as other SSRIs. It is thought that suppression of growth hormones during SSRI therapy has some connection, due to the fact that secretion of growth hormones may normalize after stopping drug therapy.10

Sexual dysfunction:  Sexual dysfunction is the most prevalent reason people decide to stop SSRI therapy. Inability to reach orgasm, loss of interest in sex, and erectile dysfunction are all common manifestations. These symptoms typically normalize after the drug is stopped. In cases of priapism (painful sustained erection) taking short “drug holidays” has become the usual “treatment,” although sometimes surgery is necessary to avoid permanent damage, especially in children.11,15,17,18

Changes to weight:  Weight gain or weight loss is commonly reported with long-term antidepressant use. Prozac is more commonly associated with weight loss. Increases and decreases in body temperature and energy expenditure while at rest, as well as changes to appetite, are the suggested causes of weight fluctuations, according to clinical research.12,13

Risks in pregnancy:  Heart defects are associated with infants born to mothers taking Prozac past the 20th week of pregnancy. Prenatal exposure to SSRIs increases the likelihood of symptoms of autism. Preeclampsia (life-threatening multi-organ failure) in the near-term mother is associated with taking Prozac during pregnancy.8,14

Impaired quality of life:  Whether from developing low-sodium, organ damage, cognitive decline, brain fog, apathy, mood dysregulation, loss of emotional responsiveness, altered gene expressions, or other lingering effects, the quality of one’s life can decline as a result of long-term antidepressant use.16

Tolerance:  After any drug is used for a long time, the body/brain/CNS will develop tolerance. Tolerance happens after neuroadaptive changes, that cause the drug to become ineffective. Even after a decade of taking Prozac, the drug may suddenly stop working as it once did and the original symptoms are not able to be masked anymore. This is often called “relapse” and is typically a point where a prescriber will increase the dose or add additional medications to continue suppressing problematic symptoms. This practice, though common, ultimately leads to worsening health conditions.21,22

Prozac Prescribing Information

prozac prescribing infoDue to its relatively long half-life, Prozac is typically prescribed daily. An enteric-coated extended-release version for maintenance treatment is prescribed once every 7 days.4,18

Prozac is the only SSRI not banned for children, despite the black box warning for increased suicidality.

Prozac is FDA-approved for cases of depression, bulimia, obsessive-compulsive disorder, and panic attacks.

Off-label prescribing practices are common, though adverse effects like dizziness, fatigue, insomnia, and nausea often make such practices untenable, especially in long-term use. Some examples include reawakening sexual appetite in the elderly, premature ejaculation, weight loss, and premenstrual symptoms.19,20

FAQs About Long-Term Prozac Use

What happens when you stop taking Prozac after long-term use?

You should not abruptly stop taking Prozac. Cessation should be well-supervised and done in a slow and gradual manner to avoid harsh discontinuation symptoms. More information on safely stopping Prozac can be found on the Alternative to Meds website.

Is liver or other damage reversible after long-term Prozac use?

In many cases, toxicity can be reversed by discontinuing the drug. The longer one is taking a drug that is injuring the body, the more likely it will be that the effects cannot be reversed.21

What is the placebo effect?

From about 1750, the placebo found a place in medicine as a way to respond to patients demanding treatment when no specific therapy was available or known. A placebo is the gold standard in clinical trials to measure drug effects. Sometimes placebo is called a sugar or bread pill. The fascinating thing is that centuries of observations and decades of clinical studies have found an impressive 35-40% of patients with depression treated with a placebo alone recover.24

What drugs should be avoided while taking Prozac?

There are many drugs to avoid concurrent with an SSRI. Sometimes one drug will lessen or amplify the effect of another. Serotonergic drugs should not be combined because there is a risk of too much serotonin becoming active which can be life-threatening. Abruptly switching drugs can have unexpected results — it may take time for one drug to “wash out” before colliding with a new one. Always let your prescriber know exactly what drugs you are taking so these risks can be avoided.4

Are there holistic drug-free therapies for depression and other symptoms?

A multitude of drug-free strategies available for treating depression and other unwanted symptoms can be utilized that have proven efficacy, including CBT personal or group counseling, correction of the diet, testing for food allergies and toxic exposures, exercise, yoga, Qi Gong, neurotoxin removal, and numerous other drug-free ways.2

Holistic Treatment at Alternative to Meds

help with prozac long term effectsAlternative to Meds Center has been in operation for nearly 20 years, helping people to successfully come off medication and improve their mental health after long-term medication use. While an antidepressant may have been the correct choice during a mental health crisis, medication as a long-term solution is full of unnecessary risks.

What is often overlooked in a crisis situation is taking the time to isolate what factors may have precipitated the condition or symptom, and addressing them. This is the approach that Alternative to Meds Center uses to sort out and resolve symptoms that could arise from various precursors. These can include nutritional deficiencies, exposure to toxins, stress, sleep deficiency, genetic factors, and many others.

In addition to discovering and resolving the precursors, the after-effects of long-term medication also need to be resolved. And, safe and gradual cessation is another foundational step in our treatment programs. A wide palette of therapies is used to achieve these important goals in treatment which can be viewed on our services overview pages. Please take some time to look these over. There is a lot to know about holistic protocols and why we have chosen the ones that we use, and we are happy to assist you in researching these. Call us if you have more questions about how our comprehensive recovery programs work. We treat the long-term effects of Prozac on every level possible, to help clients regain a positive outlook, resolve unwanted symptoms, and improve mental health naturally.

1. Fortune Business Insights Antidepressants Market Size published online March 2021 [cited 21 Nov 2022]

2. Valuck RJ, Libby AM, Orton HD, Morrato EH, Allen R, Baldessarini RJ. Spillover effects on treatment of adult depression in primary care after FDA advisory on risk of pediatric suicidality with SSRIs. Am J Psychiatry. 2007 Aug;164(8):1198-205. doi: 10.1176/appi.ajp.2007.07010007. PMID: 17671282. [cited 21 Nov 2022]

3. Valuck R, Annual Rates of Depression in the Adult General Managed Care Enrollee Population published by Research Gate Sept 2007 [cited 21 Nov 2022]

4. FDA label Prozac (fluoxetine capsules, delayed-release capsules) init. approved 1987 [cited 21 Nov 2022]

5. Sub Laban T, Saadabadi A. Monoamine Oxidase Inhibitors (MAOI) [Updated 2022 Jul 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 21 Nov 2022]

6. Moncrieff J. Against the stream: Antidepressants are not antidepressants – an alternative approach to drug action and implications for the use of antidepressants. BJPsych Bull. 2018 Feb;42(1):42-44. doi: 10.1192/bjb.2017.11. PMID: 29388527; PMCID: PMC6001865. [cited 21 Nov 2022]

7. Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin theory of depression: a systematic umbrella review of the evidenceMol Psychiatry(2022). [cited 18 Nov 2022]

8. Sohel AJ, Shutter MC, Molla M. Fluoxetine. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 21 Nov 2022]

9. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Fluoxetine. [Updated 2018 Feb 2]. Available from: [cited 21 Nov 2022]

10. Weintrob N, Cohen D, Klipper-Aurbach Y, Zadik Z, Dickerman Z. Decreased growth during therapy with selective serotonin reuptake inhibitors. Arch Pediatr Adolesc Med. 2002 Jul;156(7):696-701. doi: 10.1001/archpedi.156.7.696. PMID: 12090838. [cited 21 Nov 2022]

11. Cartwright C, Gibson K, Read J, Cowan O, Dehar T. Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient Prefer Adherence. 2016 Jul 28;10:1401-7. doi: 10.2147/PPA.S110632. PMID: 27528803; PMCID: PMC4970636. [cited 21 Nov 2022]

12. Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry. 2010 Oct;71(10):1259-72. doi: 10.4088/JCP.09r05346blu. PMID: 21062615. [cited 21 Nov 2022]

13. Bross R, Hoffer LJ. Fluoxetine increases resting energy expenditure and basal body temperature in humans. Am J Clin Nutr. 1995 May;61(5):1020-5. doi: 10.1093/ajcn/61.4.1020. PMID: 7733022. [cited 21 Nov 2022]

14. Karrar SA, Hong PL. Preeclampsia. [Updated 2022 Jun 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 18 Nov 2022]

15. University of Southern California patient Information Sheet, Drugs Reported to Cause Priapism published online ND [cited 21 Nov 2022]

16. Kroeze Y, Peeters D, Boulle F, Pawluski JL, van den Hove DL, van Bokhoven H, Zhou H, Homberg JR. Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus. Transl Psychiatry. 2015 Sep 22;5(9):e642. doi: 10.1038/tp.2015.145. Erratum in: Transl Psychiatry. 2016;6:e779. Pawluski, JL [Added]. PMID: 26393488; PMCID: PMC5068807. [cited 21 Nov 2022]

17. Atmaca M. Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction: Current Management Perspectives. Neuropsychiatr Dis Treat. 2020 Apr 20;16:1043-1050. doi: 10.2147/NDT.S185757. PMID: 32368066; PMCID: PMC7182464. [cited 21 Nov 2022]

18. de Klerk E. Patient compliance with enteric-coated weekly fluoxetine during continuation treatment of major depressive disorder. J Clin Psychiatry. 2001;62 Suppl 22:43-7. PMID: 11599648. [cited 21 Nov 2022]

19. Stone KJ, Viera AJ, Parman CL. Off-label applications for SSRIs. Am Fam Physician. 2003 Aug 1;68(3):498-504. PMID: 12924832. [cited 21 Nov 2022]

20. Serralde-Zúñiga AE, Gonzalez Garay AG, Rodríguez-Carmona Y, Melendez G. Fluoxetine for adults who are overweight or obese. Cochrane Database Syst Rev. 2019 Oct 15;10(10):CD011688. doi: 10.1002/14651858.CD011688.pub2. Epub ahead of print. PMID: 31613390; PMCID: PMC6792438. [cited 21 Nov 2022]

21. Buchman N, Strous RD, Baruch Y. Side effects of long-term treatment with fluoxetine. Clin Neuropharmacol. 2002 Jan-Feb;25(1):55-7. doi: 10.1097/00002826-200201000-00010. PMID: 11852298. [cited 21 Nov 2022]

22. Pietrzykowski AZ, Treistman SN. The molecular basis of tolerance. Alcohol Res Health. 2008;31(4):298-309. PMID: 23584007; PMCID: PMC3860466. [cited 21 Nov 2022]

23. Jütte R. The early history of the placebo. Complement Ther Med. 2013 Apr;21(2):94-7. doi: 10.1016/j.ctim.2012.06.002. Epub 2012 Jul 9. PMID: 23497809. [cited 21 Nov 2022]

24. Jones BDM, Razza LB, Weissman CR, et al. Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults: A Systematic Review and Meta-analysis. JAMA Netw Open. 2021;4(9):e2125531. doi:10.1001/jamanetworkopen.2021.25531 [cited 21 Nov 2022]

25. FDA drug label Sarafem (fluoxetine hydrochloride oral capsules) approved 1987 [cited 2022 Nov 21]

Originally Published November 19, 2022 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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Your Guide to the Long-term Effects of Prozac
Medical Disclaimer:
Nothing on this Website is intended to be taken as medical advice. The information provided on the website is intended to encourage, not replace, direct patient-health professional relationships. Always consult with your doctor before altering your medications. Adding nutritional supplements may alter the effect of medication. Any medication changes should be done only after proper evaluation and under medical supervision.

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