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Long-Term Effects of Zoloft on Your Brain & Body

Last Updated on May 13, 2026 by Carol Gillette

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

Zoloft (sertraline) is commonly prescribed for depression and anxiety, but long-term use can have varying effects on your brain and body. Learn more about the long-term effects of sertraline, including potential impacts on your mental and physical health over time.

Working together to establish a care plan with your doctor is one of the first steps to successfully treating the symptoms of any mental health issue.


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What Is Sertraline?

Sertraline, commonly referred to by its brand name, Zoloft, is an antidepressant medication used to treat various mental health concerns ranging from obsessive-compulsive disorder (OCD) to general depression and anxiety-related disorders. It is sometimes prescribed intermittently for PMDD symptoms. Just like any selective serotonin reuptake inhibitors (SSRIs), treatment regimens that involve Zoloft require daily doses of the drug. Most users take the medication once in the morning or once in the evening. The mechanism of how SSRI antidepressants work is not fully understood but they are thought to coax the CNS to accumulate or suspend serotonin over time.

How Does Sertraline Work?

The drug’s label states that how sertraline works is unknown.

if you must take an SSRI drug, do your due diligence, choose carefullySerotonin is a critical chemical messenger created by and in the body, that helps regulate mood, the sleep-wake cycle, and countless other functions, and is most often associated with feeling well. Drugmakers and regulators do not know exactly how SSRIs work, but claim the drug increases active serotonin in certain areas of the brain. This is a popular half truth. No drug creates serotonin. What antidepressants like sertraline do is cause existing serotonin to linger at the synapse, instead of continuing along nerve channels as usual. The theory is that this pooling effect can lead to positive effects on mood. Unfortunately, these trapped molecules eventually break down and become lost as waste material, leaving a potential deficiency over time. This is, at least in part, why long-term use of SSRIs like Zoloft can be harmful and can worsen already hard-to-manage symptoms of depression and anxiety.

Unfortunately, many mental health practitioners look to these remedies as a default treatment plan for mood disorders. In fact, no single prescription medication is a perfect fit for every person, and oftentimes, medications that work for one individual can have a negative impact on another. Gambling with potential negative side effects, especially with medication that can significantly disrupt brain chemistry, can be very dangerous and researchers agree long-term use will often cause more harm than good.2,16

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Pros vs. Cons of Long-Term Antidepressant Use

Although short-term use of antidepressants is advertised to be helpful in alleviating symptoms, there is little scientific evidence to demonstrate its efficacy in reducing symptoms of depression or anxiety, according to the National Institute for Health Research.17 Worse, when used long-term, antidepressants can have severely damaging effects on your health for years to come. When it comes to Zoloft, it is important to look at the pros and cons of this treatment plan before considering an antidepressant prescription.

Drug-based treatment attempts to use prescription antidepressants, and mood stabilizers, to chemically treat mental illness.

However, some research suggests staying on antidepressants for life or even using them long-term, can be harmful to your mind and body. In many instances, extended use can leave you worse off than before. Like all SSRIs, the FDA requires a suicide warning for people under the age of 25 on the package label.1 Fortunately, there are other holistic treatment plans that can effectively help treat your mental illness without the possible adverse long-term side effects of Zoloft.

Limited Potential for Reduction in Symptoms

Zoloft is prescribed to improve mood and mitigate symptoms. As hopeful as this theory seems, over time, most patients find they need to continue to increase their Zoloft dosage to attain even minor results. Some research has shown that such results results may be mostly attributed to the placebo effect.18 Zoloft’s adverse side effects may eventually outweigh any positive changes experienced.

Disadvantages of antidepressant use include the following:
  • Serotonin syndrome
  • Worsening of symptoms
  • Harmful drug interactions
  • Zoloft dependence and withdrawal

Serotonin Syndrome

Taking an SSRI causes an artificial accumulation of serotonin. Too much active serotonin can result in serotonin syndrome. While serotonin is naturally present in your body, unnaturally high levels of this neurotransmitter can cause serious health complications. Ranging from mild symptoms such as chills and gastrointestinal issues to seizures and even death, excess serotonin buildup from sertraline use can be life-threatening.3

Worsening of Symptoms

No SSRI can be expected to fully relieve any mental illness. However, prescription drug companies often infer such. For that reason, patients often experience disappointment during their attempts to find an antidepressant that addresses their symptoms. While trying different prescriptions, the severity of your symptoms can be dramatically worsened due to adverse reactions to medications, leaving you in a more vulnerable position than you were previously. In the time it takes for you to begin an antidepressant regime, realize the medication is incompatible with you, and start another medication, your symptoms could grow increasingly worse than before you started taking SSRIs.

Harmful Drug Interactions

As with any new prescriptions, potential interactions with your current medications are a known potential risk. An example of an adverse drug interaction is Zoloft and aspirin, which can cause increased, heavy bleeding in patients taking both. It’s also dangerous to mix Zoloft with St. John’s Wort or with MAOIS medications (monoamine oxidase inhibitors). In fact, there are so many possible adverse drug interactions with SSRIs that often it is left up to the pharmacist to determine the risks for patients, as doctors are largely under-educated in the subject.4,8,9

Zoloft Dependence and Withdrawal

Since Zoloft blocks the natural reuptake of serotonin by the nervous system and forces unnatural levels of the hormone to accumulate, your body can become dependent on its effects to sustain a feeling of normalcy. Zoloft is a mind-altering chemical and can cause you to feel withdrawals when you abruptly or even gradually discontinue its use—even if you’ve done so to avoid the negative side effects of long-term use listed above. For this reason, it is critical to consult with a healthcare provider who has familiarity with the subject to gradually taper your use of Zoloft to zero. Doing a controlled, gradual taper can reduce the withdrawals you feel when ceasing your use of the drug.

As you can see, the various drug interactions, harmful side effects, and life-threatening conditions tied to prolonged use of antidepressants like Zoloft outweigh the minimal benefits. As with any condition, there are numerous alternative treatment plans available for depression and other mental health conditions Zoloft was approved to treat. These offer a safer, more holistic option for addressing your mental health.

How Long Does It Take for Zoloft Side Effects to Go Away?

A person taking Zoloft for a very short time may be able to stop taking it with mild withdrawal symptoms or may experience none at all. For example, women may be prescribed low-dose sertraline (100-150 mg) for premenstrual issues. For PMDD, Zoloft is to be taken for 14 days until the start of their period, and then the drug is discontinued. No long-term trials have ever been done specifically on whether drug withdrawals occurred after intermittent use. We do know that Zoloft discontinuation syndrome was not reported in association with several 2-week and 6-week trials of using Zoloft and other SSRIs intermittently for PMDD. Drug side effects were reported, however, and were generally observed to quickly fade as the drug is excreted from the system, over a few days. In a short-term trial published in the Journal Obstet Gynecol, 8% of PMDD participants dropped out because of adverse effects. In a similar clinical trial, the most common adverse effects were nausea, loss of libido, sweating, and tiredness.10-13

Dosage, Dependence, Withdrawals

As with any psychoactive drug, the severity of the side effects associated with Zoloft use can vary based on your body’s unique interactions with the drug, dosage, as well as length of use. Dose-related adverse effects of Zoloft have been reported, such as the emergence of hypomania at 300 mg/day, which was reversed once the dosage was lowered to 200 mg/day.14 The FDA suggests that if a patient does not improve after 24 continuous weeks of Zoloft treatment, the dose be titrated upwards to see if the patient will see improvement at a higher dose.6 This practice may lead to dependence. Once dependence develops, withdrawal symptoms will occur if a dose is missed or delayed, or the drug is abruptly discontinued. Zoloft withdrawals may emerge within a day or two due to the drug’s short half-life (22-36 hr).19 The long list of Zoloft withdrawal symptoms is collectively referred to as Zoloft discontinuation syndrome. Zoloft withdrawals can be ongoing, resembling severe, flu-like symptoms and insomnia, and a wide range of psychiatric and other symptoms which may persist for days, weeks, months, or even years. Improperly managed withdrawal after long-term Zoloft use can keep a person locked in a vicious cycle of lingering Zoloft side effects and discontinuation syndrome for a very long time.5

Long-Term Effects of Zoloft

While even short-term Zoloft use can cause undesirable and potentially dangerous side effects, taking sertraline for an extended period may have even more severe effects on your body and mind. The long-term effects of sertraline on the brain can go far beyond discontinuation syndrome, causing physical changes like weight fluctuation and problems with your sex drive.

Dealing with the long-term effects of antidepressants can be a very serious endeavor, and symptoms can persist long after your use of the medication has stopped. Identifying a safer alternative treatment or seeking treatment medical advice for safe and proper antidepressant withdrawal are two extremely important steps on your own recovery journey. Rather than suffering adverse side effects or developing secondary syndromes as a result of SSRI use, choosing a more holistic option for treatment can help ensure you keep your body and your mind healthy.

Some of the more common long-term side effects of antidepressants include:
  • Weight gain
  • Sexual dysfunction
  • Memory loss
  • Cognitive impairment

Weight Gain

One of the most-reported side effects of SSRIs is weight gain, which can be both physically and mentally taxing. For those with body image issues, gaining weight as a result of taking an SSRI might be hard to deal with emotionally, and it can add an extra hurdle to dealing with your mental illness. In addition to the mental stress of weight gain, the physical stress of this extra weight can be detrimental to overall health.20

Sexual Dysfunction

Another often reported adverse effect of antidepressant use is sexual dysfunction, which is called PSSD. PSSD stands for post-SSRI/SNRI-sexual-dysfunction.  Both male and female sexual organs can become anesthetized, numb, and unresponsive, which conditions can persist even after discontinuation of the antidepressant.6,21

Memory Loss and Cognitive Impairment

Studies ranging in length from 35 days to 8 weeks, and to 6 months showed statistically significant memory loss and cognitive impairment in a wide age range of participants (aged 20-60). Zoloft appears to slow cognitive function and may worsen existing memory deterioration.7,15

Antidepressants of many forms have been shown associated with a 2-fold increase in cognitive impairment including dementia and Alzheimer disease — particularly if the antidepressants were started before age 65.20

Alternatives to Prescription Zoloft

Holistic-minded healthcare professionals may incorporate talk therapy like cognitive behavioral therapy, trauma therapy, and a wide range of other strategies and tools learned throughout the recovery process into a comprehensive plan for improvement.

A wide range of holistic alternatives to Zoloft can help you address your mental illness while keeping your body and brain healthy. For example, stimulating physical activities, such as yoga or Qi Gong, can help you naturally release negative emotions and anxiety in your system by utilizing key stretches and workout techniques aimed at opening up the body.

Some alternatives such as Reiki or art therapy courses, can help you connect to your natural, spiritual self and promote healing from within. Spiritual practices may also benefit you in your personal journey. Neurotoxins have detrimental effects on mental and physical health, and neurotoxin removal is another recommended alternative treatment. Diet is extremely important in recovery after antidepressant use, and may also benefit your original symptoms for which Zoloft was prescribed, but did not adequately help.

Finally, consider pursuing holistic treatment that incorporates some or all these alternatives. Look for a provider that offers talk therapy such as cognitive-behavioral therapy, art therapy, acupuncture, peer support programs, IV nutrient therapy, and more. Then, ask how you can adjust your own personal nutrition and physical activity to increase your serotonin naturally.

Find the Right Kind of Help

While Zoloft is approved to treat depression and a number of other conditions, the mechanism by which it works is not fully understood. The efficacy of Zoloft to treat major depressive disorder or other symptoms has been questioned, according to recent research published in The Lancet and older research published in the Journal of Clinical Pharmacokinetics some 20 years ago.17,19 Antidepressants are linked to a number of adverse side effects, including clinical worsening, sexual dysfunction, suicidality, and many others. There may be safer alternatives besides taking Zoloft long-term to treat your symptoms, and resources are available for safe withdrawal and healthy recovery. Contact us today for more information on how our inpatient program may be your best option to overcome the long-term effects of Zoloft.

Zoloft Long-Term Effects FAQs

What are the long-term effects of sertraline on the brain?

Long-term use of sertraline may lead to side effects such as sexual dysfunction, weight gain, and emotional blunting. In rare cases, serotonin syndrome can occur, which is life-threatening. Regular consultation with a healthcare provider who specializes in psychiatry is essential.

What side effects can occur with long-term sertraline use?

Common side effects of long-term sertraline use include sexual dysfunction, weight gain, and gastrointestinal issues. Serious side effects can include suicidal thoughts and an increased risk of worsening symptoms in conditions like post-traumatic stress disorder (PTSD) or bipolar disorder.

How does sertraline compare to other antidepressants like fluoxetine or paroxetine?

Sertraline, fluoxetine, and paroxetine are all SSRIs, but their side effect profiles differ. Fluoxetine has a longer half-life, while paroxetine may cause more sexual side effects. Additionally, each person can have distinct side effect profile unique to them.  A healthcare provider can help determine the best choice based on your needs.

Is it safe to stop sertraline abruptly?

No. Stopping sertraline suddenly can lead to withdrawal symptoms such as dizziness, nausea, and irritability. It’s important to consult with a healthcare provider before making any changes to your medication regimen to avoid adverse effects.

How does sertraline affect mental health conditions like anxiety and OCD?

Sertraline is prescribed to treat anxiety disorders and obsessive-compulsive disorder (OCD) but the mechanisms are unknown. 

What should I do if I experience side effects from sertraline?

If you experience side effects such as sexual dysfunction, suicidality, weight changes, or mood swings, consult your healthcare provider. They may adjust your dosage or recommend alternative treatments based on your specific symptoms and concerns.

Sources:


1. Medline Plus (2022). Sertraline. National Library of Medicine. [cited 2026 May 13]

2. Danborg PB, Valdersdorf M, Gøtzsche PC. Long-term harms from previous use of selective serotonin reuptake inhibitors: A systematic review. Int J Risk Saf Med. 2019;30(2):59-71. doi: 10.3233/JRS-180046. PMID: 30714974; PMCID: PMC6839490.[cited 2026 May 13]

3. Martin TG. Serotonin syndrome. Ann Emerg Med. 1996 Nov;28(5):520-6. doi: 10.1016/s0196-0644(96)70116-6. PMID: 8909274.[cited 2026 May 13]

4. College of Psychiatric and Neurologic Pharmacists, National Alliance on Mental Illness (2020) Sertraline (Zoloft). NAMI: National Alliance on Mental Illness.[cited 2026 May 13]

5. Warner, C. H., Bobo, W., Warner, C., Reid, S., & Rachal, J. (2006). Antidepressant discontinuation syndrome. American family physician, 74(3), 449–456.[cited 2026 May 13]

6. Masand, P. S., & Gupta, S. (2002). Long-term side effects of newer-generation antidepressants: SSRIS, venlafaxine, nefazodone, bupropion, and mirtazapine. Annals of Clinical Psychiatry, 14(3), 175-182. [cited 2026 May 13]

7. Sayyah M, Eslami K, AlaiShehni S, Kouti L. Cognitive Function before and during Treatment with Selective Serotonin Reuptake Inhibitors in Patients with Depression or Obsessive-Compulsive Disorder. Psychiatry J. 2016;2016:5480391. doi:10.1155/2016/5480391 [cited 2026 May 13]

8. FDA Drug Label Zoloft (sertraline hydrochloride) tablets, oral solution [cited 2026 May 13]

9. Charles H. Brown, RPh, MS Pharm, CACP Professor Emeritus of Clinical Pharmacy Purdue University School of Pharmacy and Pharmaceutical Sciences West Lafayette, Indiana. Overview of Drug Interactions with SSRIs.  US Pharm. 2008;33(1):HS-3-HS-19. [published online 2008 Jan 23] [cited 2026 May 13]

10. Singh HK, Saadabadi A. Sertraline. [Updated 2022 May 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547689/ [cited 2026 May 13]

11. Halbreich U, Bergeron R, Yonkers KA, Freeman E, Stout AL, Cohen L. Efficacy of intermittent, luteal phase sertraline treatment of premenstrual dysphoric disorder. Obstet Gynecol. 2002 Dec;100(6):1219-29. doi: 10.1016/s0029-7844(02)02326-8. PMID: 12468166. [cited 2026 May 13]

12. Marjoribanks J, Brown J, O’Brien PM, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev. 2013 Jun 7;2013(6):CD001396. doi: 10.1002/14651858.CD001396.pub3. PMID: 23744611; PMCID: PMC7073417. [cited 2026 May 13]

13. Halbreich U, Kahn LS. Treatment of premenstrual dysphoric disorder with luteal phase dosing of sertraline. Expert Opin Pharmacother. 2003 Nov;4(11):2065-78. doi: 10.1517/14656566.4.11.2065. PMID: 14596660.[cited 2026 May 13]

14. Ramasubbu R. Dose-response relationship of selective serotonin reuptake inhibitors treatment-emergent hypomania in depressive disorders. Acta Psychiatr Scand. 2001 Sep;104(3):236-8; discusiion 238-9. doi: 10.1034/j.1600-0447.2001.00383.x. PMID: 11531662.[cited 2026 May 13]

15. Popovic D, Vieta E, Fornaro M, Perugi G. Cognitive tolerability following successful long term treatment of major depression and anxiety disorders with SSRi antidepressants. J Affect Disord. 2015 Mar 1;173:211-5. doi: 10.1016/j.jad.2014.11.008. Epub 2014 Nov 15. PMID: 25462418.[cited 2026 May 13]

16. Siesser WB, Sachs BD, Ramsey AJ, et al. Chronic SSRI treatment exacerbates serotonin deficiency in humanized Tph2 mutant miceACS Chem Neurosci. 2013;4(1):84-88. doi:10.1021/cn300127h [cited 2026 May 13]

17. Lewis G, Duffy L, et al, The clinical effectiveness of sertraline in primary care and the role of depression severity and duration (PANDA): a pragmatic, double-blind, placebo-controlled, randomised trial. The Lancet Sept 19, 2019 [cited 2026 May 13]

18. Kirsch I. Antidepressants and the Placebo Effect. Z Psychol. 2014;222(3):128-134. doi: 10.1027/2151-2604/a000176. PMID: 25279271; PMCID: PMC4172306. [cited 2026 May 13]

19. DeVane CL, Liston HL, Markowitz JS. Clinical pharmacokinetics of sertraline. Clin Pharmacokinet. 2002;41(15):1247-66. doi: 10.2165/00003088-200241150-00002. PMID: 12452737.[cited 2026 May 13]

20. Shi Z, Atlantis E, Taylor AW, et al. SSRI antidepressant use potentiates weight gain in the context of unhealthy lifestyles: results from a 4-year Australian follow-up studyBMJ Open. 2017;7(8):e016224. Published 2017 Aug 11. doi:10.1136/bmjopen-2017-016224 [cited 2026 May 13]

20. Moraros J, Nwankwo C, Patten SB, Mousseau DD. The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta-analysis. Depress Anxiety. 2017 Mar;34(3):217-226. doi: 10.1002/da.22584. Epub 2016 Dec 28. PMID: 28029715; PMCID: PMC5347943.  [cited 2026 May 13]

21. Ben-Sheetrit J, Aizenberg D, Csoka AB, Weizman A, Hermesh H. Post-SSRI Sexual Dysfunction: Clinical Characterization and Preliminary Assessment of Contributory Factors and Dose-Response Relationship. J Clin Psychopharmacol. 2015 Jun;35(3):273-8. doi: 10.1097/JCP.0000000000000300. PMID: 25815755. [cited 2026 May 13]



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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