Call Mon-Sun:
1 (800) 301-3753
Alternative to Meds News & Blog Articles

Long-Term Effects of Zoloft on Your Body

Last Updated on November 4, 2023 by Carol Gillette

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

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. Holistic-minded professionals may incorporate talk therapy like cognitive behavioral therapy, trauma therapy, and other coping tools learned throughout the recovery process into a comprehensive plan for improvement. Drug-based treatment attempts to use prescription antidepressants, and mood stabilizers, to chemically treat mental illness.

However, 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 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.

What Is Sertraline?

Sertraline, commonly referred to by its name-brand label, Zoloft, is an antidepressant drug 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 this medication works is not fully understood but is thought to coax the CNS to accumulate or suspend serotonin over time.

How Does Sertraline Work?

Serotonin is a critical chemical messenger 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 they are theorized to increase active serotonin in certain areas of the brain that may have positive effects on mood. Unfortunately, these 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 mental illness. 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 permanently alter your brain chemistry, can be very dangerous and researchers agree long-term use will often cause more harm than good.2,16

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.

15 Years Experience by Professionals Who Understand Your Journey.
Up to 87 ½% Long-Term Success Rate.
Click to Call7 Days a Week

  • By completing this form, you will be added to our mailing list. You may opt out at any time.
  • Hidden
  • This field is for validation purposes and should be left unchanged.

Limited Potential for Reduction in Symptoms

Using antidepressants like Zoloft should theoretically increase your mood and mitigate your 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 even those results may be mostly attributed to the placebo effect.18 Zoloft’s adverse side effects may eventually outweigh any positive changes you may have 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. 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.10,11,12,13

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.

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. While increasing the level of serotonin in your brain might seem like a good idea, antidepressants actually suppress the necessary neuroreceptors and chemicals responsible for libido. This can cause tension in your relationships and personal life as well as physical discomfort.6

Memory Issues

Studies ranging in length from 35 days to 8 weeks, 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

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 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.

Alternatives to Prescription Zoloft

Although prescriptions are readily available, they should not be used as a “one size fits all” treatment—or even the first option to treat various mental health conditions. More holistic approaches and 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.

Other alternatives to Zoloft include equine-assisted therapy and massage therapy.

Some less-taxing treatment methods, 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 causes an accumulation of serotonin is not fully understood. The efficacy of Zoloft to treat depression or other symptoms is questionable at best, according to recent research published in The Lancet and more research published in the Journal of Clinical Pharmacokinetics some 20 years ago.17,19 Alternative to Meds Center knows antidepressants are linked to a number of adverse side effects, including clinical worsening, and suicidality. Taking Zoloft long-term to treat your depression, may not be the best path forward. Contact us today for more information on how our inpatient program may be your best option to overcome the long-term effects of Zoloft.


1. Medline Plus (2022). Sertraline. National Library of Medicine. [cited 2022 Jun 3]

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 2022 Jun 3]

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 2022 Jun 3]

4. College of Psychiatric and Neurologic Pharmacists, National Alliance on Mental Illness (2020) Sertraline (Zoloft). NAMI: National Alliance on Mental Illness. [cited 2022 Jun 3]

5. Warner, C. H., Bobo, W., Warner, C., Reid, S., & Rachal, J. (2006). Antidepressant discontinuation syndrome. American family physician, 74(3), 449–456. [cited 2022 Jun 3]

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 2022 Jun 3]

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 2022 June 3]

8. FDA Drug Label Zoloft (sertraline hydrochloride) tablets, oral solution [cited 2022 June 3]

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 2022 Jun 3]

10. Singh HK, Saadabadi A. Sertraline. [Updated 2022 May 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [cited 2022 Jun 3]

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 2022 Jun 3]

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 2022 Jun 3]

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 2022 Jun 3]

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 2022 Jun 3]

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 2022 Jun 3]

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 2022 Jun 3]

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 2022 Jun 3]

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 2022 Jun 3]

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 2022 Jun 3]

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 2022 Jun 3]

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.

Social Profile: LinkedIn

View Bio

Long-Term Effects of Zoloft on Your Body
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.

We Accept Most PPO Insurance Plans for Partial Coverage of Fees

Call Now to Verify BlueCross BlueShield Cigna Aetna

Our Success Stories

Medication Withdrawal Success Stories

Can you imagine being free from medications, addictive drugs, and alcohol? This is our goal and we are proving it is possible every day!

Read All StoriesView All Videos