Long-Term Effects of Zoloft on Your Brain & Body

Alternative to Meds Editorial Team
Medically Reviewed by Dr John Motl MD

Long-term side effects of Zoloft (sertraline)

Zoloft (sertraline) is an SSRI antidepressant prescribed for depression, anxiety, and OCD. Taken for months or years, it can affect both brain and body. The most reported long-term effects are weight gain, sexual dysfunction, memory loss, and slower thinking.^6,7,20 Some people also notice emotional blunting.

Your body can also become dependent on Zoloft, so stopping can cause withdrawal, called discontinuation syndrome.⁵ Some effects, such as sexual dysfunction, can persist even after the drug is stopped.^6,22

Long-term effects at a glance:

• Brain and mood: memory loss, cognitive impairment, emotional blunting, worsening of symptoms, and in some cases hypomania at high doses.^7,14,15
• Weight: weight gain is one of the most-reported SSRI side effects.²⁰
• Sexual health: numbness and loss of response in both men and women, which can last after stopping (PSSD).^6,22
• Serious risks: serotonin syndrome, harmful drug interactions, and an FDA suicide warning for people under 25.^1,3,4
• Dependence: withdrawal symptoms if a dose is missed, delayed, or stopped abruptly.⁵

Long-term effects of sertraline on the brain

How sertraline works

The drug’s label states that how sertraline works is unknown. Serotonin is a chemical messenger your body makes. It helps regulate mood, the sleep-wake cycle, and many other functions.

SSRIs are said to increase active serotonin in the brain, but no drug creates serotonin. Sertraline causes existing serotonin to linger at the synapse instead of moving on as usual. Over time, those trapped molecules break down and are lost as waste, which may leave a deficiency.¹⁶ This is, at least in part, why long-term SSRI use can be harmful and can worsen depression and anxiety.^2,16

Memory loss and cognitive impairment

Studies lasting from 35 days to 8 weeks, and up to 6 months, found statistically significant memory loss and cognitive impairment in adults aged 20 to 60. Zoloft appears to slow thinking and may worsen existing memory problems.^7,15

Dementia risk: many kinds of antidepressants have been associated with a 2-fold increase in cognitive impairment, including dementia and Alzheimer disease. The link was strongest when antidepressants were started before age 65.²¹

Mood changes and worsening symptoms

• Emotional blunting: some long-term users describe feeling flat or numb.
• Worsening symptoms: no SSRI can be expected to fully relieve a mental illness. Adverse reactions while trying different prescriptions can leave a person worse off than before.
• Hypomania at high doses: hypomania has been reported at 300 mg/day and reversed when the dose was lowered to 200 mg/day.¹⁴
• Suicide warning: like all SSRIs, Zoloft carries an FDA suicide warning for people under 25.¹

Does Zoloft change your brain permanently?

The research does not give a simple yes or no. What it does show is that some effects of long-term SSRI use can last well after the medication is stopped.²

• Serotonin supply: in animal research, chronic SSRI treatment made an existing serotonin deficiency worse.¹⁶
• Sexual function: PSSD can persist after the antidepressant is discontinued.^6,22
• Withdrawal: poorly managed withdrawal after long-term use can bring symptoms that last weeks, months, or even years.⁵
• Memory and thinking: the memory studies above measured people during treatment. They show impairment while on the drug, but they don’t settle whether it is permanent.^7,15

If you’re worried about how Zoloft is affecting your brain, read more in Is Zoloft harming your brain?

Long-term effects of Zoloft on the body

Sertraline’s side effects go beyond mood. Over time, they can show up as physical changes that affect daily life.

• Weight gain: one of the most-reported SSRI side effects. It can be physically and emotionally taxing, especially for anyone with body image concerns, and the extra weight can strain overall health.²⁰
• Sexual dysfunction (PSSD): post-SSRI/SNRI sexual dysfunction. Male and female sexual organs can become numb and unresponsive, and this can persist after stopping the antidepressant.^6,22
• Digestive problems: gastrointestinal issues are a common complaint with long-term use.
• Bleeding risk: taking Zoloft with aspirin can cause increased, heavy bleeding.^4,8,9
• Other common effects: in short-term trials, the most common adverse effects were nausea, loss of libido, sweating, and tiredness.^10-13

Serotonin syndrome

Taking an SSRI causes an artificial buildup of serotonin, and too much can cause serotonin syndrome. Symptoms range from chills and stomach upset to seizures, and it can be life-threatening.³

Harmful drug interactions

Besides aspirin, it is dangerous to mix Zoloft with St. John’s Wort or with MAOI medications (monoamine oxidase inhibitors). There are so many possible SSRI interactions that it is often left to the pharmacist to judge the risks.^4,8,9

Can you take sertraline for life?

Zoloft is often taken for years, but some research suggests staying on antidepressants for life, or even long-term, can be harmful to mind and body. In many cases, extended use can leave a person worse off than before.²

What to weigh before long-term use:

• Effectiveness over time: many people find they need higher doses to get even minor results. Some research suggests those results may be mostly due to the placebo effect.¹⁸
• Limited evidence: according to the National Institute for Health Research, there is little scientific evidence that antidepressants reduce symptoms of depression or anxiety.¹⁷
• Rising doses: the FDA suggests that if a patient doesn’t improve after 24 continuous weeks, the dose may be raised. This practice may lead to dependence.⁶
• Adding up the risks: serotonin syndrome, drug interactions, worsening symptoms, and dependence can come to outweigh the benefits.^3,4

If you’ve been on Zoloft for 10 or 20 years, you’re not alone, and it’s not too late to explore your options. Long-term use does mean coming off should be planned carefully, with support.

How long do Zoloft side effects last?

It depends mostly on how long you’ve taken it. Dose, length of use, and your body’s own response all affect how severe side effects are.

• After short-term use: some women take low-dose sertraline (100–150 mg) for PMDD for 14 days until their period starts, then stop. Discontinuation syndrome was not reported in several 2-week and 6-week trials of this kind of intermittent use.^10-13
• Side effects in those trials: they generally faded quickly, over a few days, as the drug left the system. In one trial, 8% of participants dropped out because of adverse effects.^10-13
• After long-term use: symptoms can persist long after the medication is stopped. Withdrawal may last days, weeks, months, or even years.⁵

No long-term trials have looked specifically at whether withdrawal occurs after intermittent use.

Coming off Zoloft after long-term use

Because Zoloft forces serotonin levels to build up, your body can come to depend on it to feel normal. Once dependence develops, withdrawal can occur if a dose is missed or delayed, or the drug is stopped abruptly.⁵

• When withdrawal starts: often within a day or two, because of Zoloft’s short half-life (22–36 hours).¹⁹
• What it can feel like: severe flu-like symptoms, insomnia, dizziness, nausea, irritability, and a wide range of psychiatric and other symptoms.⁵
• How long it lasts: days, weeks, months, or even years.⁵
• The cycle to avoid: improperly managed withdrawal after long-term use can lock a person into lingering side effects and discontinuation syndrome for a very long time.⁵

Withdrawal can happen whether Zoloft is stopped abruptly or even gradually. That’s why a controlled taper, guided by a provider familiar with SSRI withdrawal, matters. The right pace is different for everyone. Learn more about Zoloft tapering.

If Zoloft’s side effects are affecting your life

Reading about side effects is often the first step. The next is knowing you have options. Here are three paths people take.

1. Learn about alternatives to Zoloft. A wide range of holistic alternatives to Zoloft can help address the symptoms it was prescribed for. These include talk therapy like cognitive behavioral therapy and trauma therapy, movement such as yoga and Qi Gong, art therapy, Reiki, acupuncture, and peer support. Diet and neurotoxin removal also matter, both in recovery and for the original symptoms.

2. Come off Zoloft with supervision. At Alternative to Meds Center, every taper is individualized, never one-size-fits-all:

• Built around you, with the pace adjusted as you respond.
• Precise dosing, with each dose step planned by our medical team, using half tablets or liquid preparations as needed.
• Brain chemistry support through nutrient therapy and neurotransmitter support.
• Root causes addressed: nutrition, toxins, and counseling.
• Residential support with our clinical team on site.

3. Talk it through. A free, confidential call can help you sort out what makes sense for you. Call (888) 907-7075.

Coming off Zoloft at home vs. at ATMC

Helping a loved one who wants to come off Zoloft

Many people reading this are worried about a spouse, parent, or adult child. Your support can make a real difference.

• Listen first. Side effects like weight gain, sexual problems, emotional numbness, or memory trouble can be hard to talk about. Take them seriously.
• Discourage stopping suddenly. Withdrawal can begin within a day or two of a missed dose.¹⁹ Encourage a supervised plan instead.
• Know the warning signs. Watch for worsening mood, agitation, or signs of serotonin syndrome, and seek medical care if they appear.^1,3
• Help gather information. Make a list of their medications, doses, and how long they’ve taken Zoloft, to bring to a provider.
• Make the first call together. Many families call us first, simply to understand the options.

Find the right kind of help

Zoloft is approved for depression and several other conditions, but how it works is not fully understood. Its effectiveness for major depression has been questioned in research published in The Lancet and, some 20 years ago, in Clinical Pharmacokinetics.^17,19 There may be safer options than taking Zoloft long-term, and support is available for safe withdrawal.

Alternative to Meds Center has specialized in medication withdrawal for nearly 20 years, and our outcomes are documented in published evidence.

Our residential program in Sedona averages about 60 days. Each client’s program addresses root causes, including nutrition, toxins, and counseling, alongside an individualized taper. Learn more about antidepressant treatment and our Sedona facility.

Watch: What are the long-term effects of Zoloft?

More about sertraline

Sertraline, sold under the brand name Zoloft, is an SSRI (selective serotonin reuptake inhibitor) antidepressant.

• It’s used for conditions ranging from OCD to depression and anxiety disorders.
• It’s sometimes prescribed intermittently for PMDD.^11-13
• Like other SSRIs, it’s taken daily, usually once in the morning or once in the evening.
• No single medication is a perfect fit for everyone; a drug that helps one person can harm another.

Zoloft long-term effects FAQs

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; discussion 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 mice. ACS 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 study. BMJ Open. 2017;7(8):e016224. Published 2017 Aug 11. doi:10.1136/bmjopen-2017-016224 [cited 2026 May 13]

21. 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]

22. 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]

Originally Published May 12, 2026 by Alternative to Meds Editorial Team

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

Dr. John Motl, M.D.

Dr. Motl is currently certified by the American Board of Psychiatry and Neurology in Psychiatry, and Board eligible in Neurology and licensed in the state of Arizona.  He holds a Bachelor of Science degree with a major in biology and minors in chemistry and philosophy. He graduated from Creighton University School of Medicine with a Doctor of Medicine.  Dr. Motl has studied Medical Acupuncture at the Colorado School of Traditional Chinese Medicine and at U.C.L.A.

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Diane Ridaeus

Diane is an avid supporter and researcher of natural mental health strategies. Diane received her medical writing and science communication certification through Stanford University and has published over 3 million words on the topics of holistic health, addiction, recovery, and alternative medicine. She has proudly worked with the Alternative to Meds Center since its inception and is grateful for the opportunity to help the founding members develop this world-class center that has helped so many thousands regain natural mental health.