Long-Term Effects of Antidepressants

Table of ContentsView AllTable of ContentsEffects on the BrainWeight GainBlood Sugar & DiabetesDepressionTreatment-Resistant DepressionManaging Long-Term Use

Table of ContentsView All

View All

Table of Contents

Effects on the Brain

Weight Gain

Blood Sugar & Diabetes

Depression

Treatment-Resistant Depression

Managing Long-Term Use

Verywell / JR Bee

Side effects

The long-term side effects ofantidepressantssuch as Zoloft can include emotional numbness, sexual problems, weight gain, reduced positive feelings, and/or suicidal thoughts.Nevertheless, antidepressants such as Zoloft are often prescribed for long-term usewhen healthcare providers believe their benefits outweigh their risks.

Although this class of medications is named after a single condition, antidepressants are also used to treat many other illnesses including:

Researchers are just learning about the long-term side effects of antidepressants. Extended studies are rarely done before a drug gains approval, so medications can be around for a long time before a consistent side effect profile emerges.

Antidepressants and Your Brain

Before delving into the research, let’s look at how antidepressants work. Antidepressants come in several forms, such as:

In the brain, information—including emotion—moves from one neuron (brain cell) to another via chemical messengers calledneurotransmitters.Think of neurotransmitters as mailbox keys. Each one unlocks certain receptors (chemical “locks”) that keep the message traveling.

Negative Side Effects of Antidepressants

With many of these conditions or diseases, something is wrong with the brain’s neurotransmitters (usuallyserotonin,norepinephrine,dopamine, or others).Sometimes, there’s just not enough of one or more of the neurotransmitters. In other cases, the brain doesn’t use neurotransmitters efficiently, or the problem could lie with the receptors. There’s either no key for the lock, the key isn’t used properly, or the lock is broken.

Regardless of the cause of the problem, the result is the same: neurotransmitter dysregulation.The mail isn’t getting to the right mailbox, so messages aren’t being delivered.

Once the messages are flowing more as they should, your brain works better and the symptoms related to the slow-down diminish or go away.

Long-Term Side Effects

Every neurotransmitter has many different jobs. Increasing the available neurotransmitters might have the desired effect of alleviating depression, lowering neuropathic pain, or improving one’s thought process, but it can also have unwanted effects.

The potential side effects of Zoloft and other antidepressants are many, and they can range from mildly annoying todebilitatingand even life-threatening. Beyond that, there’s the issue of antidepressants becoming less effective over time.

As we’ve learned more about the long-term effects of antidepressants such as Zoloft, some of the top concerns that have emerged have to do with weight gain and diabetes. However, many other side effects can persist and have a negative impact on your quality of life.

Patient Preference and Adherencepublished a paper looking at what people taking antidepressants long-term had to say about the side effects that they’ve seen.Overall, they were less depressed and had a better quality of life because of the drugs, but about 30% still said they had moderate or severe depression.

The main side effects included:

Many of the participants wanted more information about the long-term risks of their medication. About 74% of people also mentionedwithdrawal symptomsand said they needed more information and support about going off of antidepressants.

Some people noted that they’d had to try multiple antidepressants before finding one that worked well for them and was tolerable. However, more than two-thirds of the people questioned said the medication helped them cope with life.

About one-fifth of the participants said antidepressants helped them to function well. However, some said that if they’d known about the side effects and possibility of withdrawal, they would never have started taking the medication at all.

Never stop taking antidepressants suddenly. Talk to your doctor about the proper way to wean off of them.

What It Means for You

Before taking Zoloft or another antidepressant, get familiar with the possible long-term side effects. Know that you may need to try several drugs before finding the best one for you.

While you’re on the medication, stay vigilant for side effects, and weigh how significant they are versus how much the drug helps you.

You should involve your doctor in any decisions you make regarding antidepressant use. That said, you’re the only one who can decide whether the benefits of taking a medication outweigh the drawbacks.

Weight gain is one of the potential long-term side effects of Zoloft and some other antidepressants on the body.

A 2015 study published inThe Journal of Clinical Psychiatrysuggests the long-term risk ofweight gainfrom antidepressants that alter serotonin receptors could be significantly higher in women than in men, possibly due to differences in how serotonin is used.

A 2015 Australian study noted that people on antidepressants tended to gain more than 3% of their body weight each year. Over time, that can really add up.

Weight gain can have negative effects on your self-esteem as well as your health. Talk to your doctor about how you may be able to improve your diet and/or increase exercise to help keep those extra pounds from piling up.

Several studies have noted what appears to be a link between antidepressant use and problems with blood sugar regulation, including type 2 diabetes.

A systematic review published in a 2013 edition of the journalDiabetes Careexamined this relationship to get a better feel for what’s going on. They looked at 22 studies, including a couple with more than 4,000 participants. Here’s a look at some of the findings that prompted the review:

The aim of the review was to determine whether antidepressants raise the risk of diabetes in people who didn’t have it when they started on the medications. They concluded that some antidepressants affect blood sugar regulation and that the drugs could be a risk factor for diabetes. However, the larger and more recent studies they looked at suggested that the risk was small.

They do say, though, that higher doses appear to be linked to greater risk. Also, in some cases, people who have developed type 2 diabetes while on antidepressants have seen the disease disappear when they went off of the medication. Researchers also note that people who were diagnosed with diabetes were more likely to be prescribed antidepressants, but the relationship there isn’t clear.

If you have diabetes, your doctor may want to adjust your diabetes medications while you’re on antidepressants to make sure your blood sugar levels are staying in a healthy range.

You might also want to focus more on weight loss and exercise since both of those things play a role in diabetes, and your antidepressant may be causing some weight gain.

If you’re concerned about your diabetes risk or have type 2 diabetes, you may want to talk to your doctor about finding an antidepressant that is less linked to blood sugar problems. You may also want to test your blood sugars more frequently.

Can Antidepressants Stop Working?

If yourantidepressant is no longer workingas well as it did when you first started taking it, you could have developed a tolerance for the drug. Some people refer to this as antidepressant “poop-out,” although the medical term is tachyphylaxis. It has not been determined how many people taking antidepressants experience this phenomenon, but studies show rates ranging from 9% to 57%.

While no one knows for sure why this decrease in effectiveness occurs, one theory suggests that receptors in the brain become less sensitive to the medication. Other culprits include:

If you think you’ve built a tolerance to your antidepressant, talk to your doctor who may suggest the following:

While the cause of TRD is still unknown, genetics, metabolic disorders, and misdiagnosis often play a role.

If your doctor has determined that you have TRD, they may try one or more of the following treatment approaches:

How to Manage Long-Term Antidepressant Use

If you notice any of the side effects mentioned (or any additional effects) of long-term antidepressant use, be sure to consult with a doctor immediately. In some cases, a doctor may alter your dosage or switch you to another antidepressant entirely.

Do not discontinue the use of antidepressants on your own. It may lead to relapse and/or withdrawal symptoms such as agitation and suicidal thoughts.

Many people attend therapy while they’re taking antidepressants. Treatment such as cognitive behavioral therapy may help you closely monitor any changes in behavior or other side effects that occur as a result of an antidepressant.

A therapist may even consult with your prescribing doctor or general practitioner in order to monitor your health while you take an antidepressant.

In some cases, a depression relapse may occur, even while you’re taking an antidepressant. A depression relapse is when your symptoms occur after a period of recovery. Talk to a doctor if you experience new or worsened symptoms of depression such as:

If you are having suicidal thoughts, contact theNational Suicide Prevention Lifelineat988for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.For more mental health resources, see ourNational Helpline Database.

If you are having suicidal thoughts, contact theNational Suicide Prevention Lifelineat988for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

For more mental health resources, see ourNational Helpline Database.

The Takeaway

As all drugs do, Zoloft and other antidepressants can have long-term side effects. Treatment is a balancing act, with you and your doctor(s) weighing the good against the bad and deciding on the next move. Make sure you’re well informed about the potential long-term side effects of Zoloft and other antidepressants so you can discuss them with your healthcare provider.

16 SourcesVerywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.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;10:1401-1407. doi:10.2147/PPA.S110632Hillhouse TM, Porter JH.A brief history of the development of antidepressant drugs: From monoamines to glutamate.Exp Clin Psychopharmacol. 2015;23(1):1–21. doi:10.1037/a0038550Skånland SS, Cieślar-Pobuda A.Off-label uses of drugs for depression.European Journal of Pharmacology. 2019;865:172732. doi:10.1016/j.ejphar.2019.172732Merck Manual.Neurotransmission.Sheffler Z, Reddy V, Pillarisetty L.Physiology, Neurotransmitters.Treasure Island, FL. StatPearls Publishing; 2020.Harmer CJ, Duman RS, Cowen PJ.How do antidepressants work? New perspectives for refining future treatment approaches.The Lancet Psychiatry. 2017;4(5):409-418. doi:10.1016/S2215-0366(17)30015-9Noordam R, Aarts N, Tiemeier H, Hofman A, Stricker BH, Visser LE.Sex-specific association between antidepressant use and body weight in a population-based study in older adults.J Clin Psychiatry.2015;76(6):e745-51. doi:10.4088/JCP.13m08896Paige E, Korda R, Kemp-casey A, Rodgers B, Dobbins T, Banks E.A record linkage study of antidepressant medication use and weight change in Australian adults.Aust N Z J Psychiatry. 2015;49(11):1029-39. doi:10.1177/0004867415607365Kinrys G, Gold AK, Pisano VD, et al.Tachyphylaxis in major depressive disorder: A review of the current state of research.Journal of Affective Disorders. 2019;245:488-497. doi:10.1016/j.jad.2018.10.357Al-harbi.Treatment-resistant depression: therapeutic trends, challenges, and future directions.PPA. Published online May 2012:369. doi:10.2147/PPA.S29716Fabbri C, Corponi F, Souery D, et al.The genetics of treatment-resistant depression: a critical review and future perspectives.International Journal of Neuropsychopharmacology. 2019;22(2):93-104. doi:10.1093/ijnp/pyy024Pan LA, Martin P, Zimmer T, et al.Neurometabolic disorders: Potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behavior.Am J Psychiatry. 2017;174(1):42-50. doi:10.1176/appi.ajp.2016.15111500Li J-M, Zhang Y, Su W-J, et al.Cognitive behavioral therapy for treatment-resistant depression: A systematic review and meta-analysis.Psychiatry Research. 2018;268:243-250. doi:10.1016/j.psychres.2018.07.020Kellner CH, Greenberg RM, Murrough JW, Bryson EO, Briggs MC, Pasculli RM.Ect in treatment-resistant depression.AJP. 2012;169(12):1238-1244. doi:10.1176/appi.ajp.2012.12050648Daly EJ, Trivedi MH, Janik A, et al.Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial.JAMA Psychiatry. 2019;76(9):893. doi:10.1001/jamapsychiatry.2019.1189Centers for Disease Control and Prevention.Mental health conditions: Depression and anxiety.Additional ReadingBarnard K, Peveler RC, Hold, RIG.Antidepressant medication as a risk factor for tye 2 diabetes and impaired glucose regulation: Systematic review.Diabetes Care. 2013; 36(10): 3337–3345. doi:10.2337/dc13-0560

16 Sources

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.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;10:1401-1407. doi:10.2147/PPA.S110632Hillhouse TM, Porter JH.A brief history of the development of antidepressant drugs: From monoamines to glutamate.Exp Clin Psychopharmacol. 2015;23(1):1–21. doi:10.1037/a0038550Skånland SS, Cieślar-Pobuda A.Off-label uses of drugs for depression.European Journal of Pharmacology. 2019;865:172732. doi:10.1016/j.ejphar.2019.172732Merck Manual.Neurotransmission.Sheffler Z, Reddy V, Pillarisetty L.Physiology, Neurotransmitters.Treasure Island, FL. StatPearls Publishing; 2020.Harmer CJ, Duman RS, Cowen PJ.How do antidepressants work? New perspectives for refining future treatment approaches.The Lancet Psychiatry. 2017;4(5):409-418. doi:10.1016/S2215-0366(17)30015-9Noordam R, Aarts N, Tiemeier H, Hofman A, Stricker BH, Visser LE.Sex-specific association between antidepressant use and body weight in a population-based study in older adults.J Clin Psychiatry.2015;76(6):e745-51. doi:10.4088/JCP.13m08896Paige E, Korda R, Kemp-casey A, Rodgers B, Dobbins T, Banks E.A record linkage study of antidepressant medication use and weight change in Australian adults.Aust N Z J Psychiatry. 2015;49(11):1029-39. doi:10.1177/0004867415607365Kinrys G, Gold AK, Pisano VD, et al.Tachyphylaxis in major depressive disorder: A review of the current state of research.Journal of Affective Disorders. 2019;245:488-497. doi:10.1016/j.jad.2018.10.357Al-harbi.Treatment-resistant depression: therapeutic trends, challenges, and future directions.PPA. Published online May 2012:369. doi:10.2147/PPA.S29716Fabbri C, Corponi F, Souery D, et al.The genetics of treatment-resistant depression: a critical review and future perspectives.International Journal of Neuropsychopharmacology. 2019;22(2):93-104. doi:10.1093/ijnp/pyy024Pan LA, Martin P, Zimmer T, et al.Neurometabolic disorders: Potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behavior.Am J Psychiatry. 2017;174(1):42-50. doi:10.1176/appi.ajp.2016.15111500Li J-M, Zhang Y, Su W-J, et al.Cognitive behavioral therapy for treatment-resistant depression: A systematic review and meta-analysis.Psychiatry Research. 2018;268:243-250. doi:10.1016/j.psychres.2018.07.020Kellner CH, Greenberg RM, Murrough JW, Bryson EO, Briggs MC, Pasculli RM.Ect in treatment-resistant depression.AJP. 2012;169(12):1238-1244. doi:10.1176/appi.ajp.2012.12050648Daly EJ, Trivedi MH, Janik A, et al.Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial.JAMA Psychiatry. 2019;76(9):893. doi:10.1001/jamapsychiatry.2019.1189Centers for Disease Control and Prevention.Mental health conditions: Depression and anxiety.Additional ReadingBarnard K, Peveler RC, Hold, RIG.Antidepressant medication as a risk factor for tye 2 diabetes and impaired glucose regulation: Systematic review.Diabetes Care. 2013; 36(10): 3337–3345. doi:10.2337/dc13-0560

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;10:1401-1407. doi:10.2147/PPA.S110632Hillhouse TM, Porter JH.A brief history of the development of antidepressant drugs: From monoamines to glutamate.Exp Clin Psychopharmacol. 2015;23(1):1–21. doi:10.1037/a0038550Skånland SS, Cieślar-Pobuda A.Off-label uses of drugs for depression.European Journal of Pharmacology. 2019;865:172732. doi:10.1016/j.ejphar.2019.172732Merck Manual.Neurotransmission.Sheffler Z, Reddy V, Pillarisetty L.Physiology, Neurotransmitters.Treasure Island, FL. StatPearls Publishing; 2020.Harmer CJ, Duman RS, Cowen PJ.How do antidepressants work? New perspectives for refining future treatment approaches.The Lancet Psychiatry. 2017;4(5):409-418. doi:10.1016/S2215-0366(17)30015-9Noordam R, Aarts N, Tiemeier H, Hofman A, Stricker BH, Visser LE.Sex-specific association between antidepressant use and body weight in a population-based study in older adults.J Clin Psychiatry.2015;76(6):e745-51. doi:10.4088/JCP.13m08896Paige E, Korda R, Kemp-casey A, Rodgers B, Dobbins T, Banks E.A record linkage study of antidepressant medication use and weight change in Australian adults.Aust N Z J Psychiatry. 2015;49(11):1029-39. doi:10.1177/0004867415607365Kinrys G, Gold AK, Pisano VD, et al.Tachyphylaxis in major depressive disorder: A review of the current state of research.Journal of Affective Disorders. 2019;245:488-497. doi:10.1016/j.jad.2018.10.357Al-harbi.Treatment-resistant depression: therapeutic trends, challenges, and future directions.PPA. Published online May 2012:369. doi:10.2147/PPA.S29716Fabbri C, Corponi F, Souery D, et al.The genetics of treatment-resistant depression: a critical review and future perspectives.International Journal of Neuropsychopharmacology. 2019;22(2):93-104. doi:10.1093/ijnp/pyy024Pan LA, Martin P, Zimmer T, et al.Neurometabolic disorders: Potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behavior.Am J Psychiatry. 2017;174(1):42-50. doi:10.1176/appi.ajp.2016.15111500Li J-M, Zhang Y, Su W-J, et al.Cognitive behavioral therapy for treatment-resistant depression: A systematic review and meta-analysis.Psychiatry Research. 2018;268:243-250. doi:10.1016/j.psychres.2018.07.020Kellner CH, Greenberg RM, Murrough JW, Bryson EO, Briggs MC, Pasculli RM.Ect in treatment-resistant depression.AJP. 2012;169(12):1238-1244. doi:10.1176/appi.ajp.2012.12050648Daly EJ, Trivedi MH, Janik A, et al.Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial.JAMA Psychiatry. 2019;76(9):893. doi:10.1001/jamapsychiatry.2019.1189Centers for Disease Control and Prevention.Mental health conditions: Depression and anxiety.

Hillhouse TM, Porter JH.A brief history of the development of antidepressant drugs: From monoamines to glutamate.Exp Clin Psychopharmacol. 2015;23(1):1–21. doi:10.1037/a0038550

Skånland SS, Cieślar-Pobuda A.Off-label uses of drugs for depression.European Journal of Pharmacology. 2019;865:172732. doi:10.1016/j.ejphar.2019.172732

Merck Manual.Neurotransmission.

Sheffler Z, Reddy V, Pillarisetty L.Physiology, Neurotransmitters.Treasure Island, FL. StatPearls Publishing; 2020.

Harmer CJ, Duman RS, Cowen PJ.How do antidepressants work? New perspectives for refining future treatment approaches.The Lancet Psychiatry. 2017;4(5):409-418. doi:10.1016/S2215-0366(17)30015-9

Noordam R, Aarts N, Tiemeier H, Hofman A, Stricker BH, Visser LE.Sex-specific association between antidepressant use and body weight in a population-based study in older adults.J Clin Psychiatry.2015;76(6):e745-51. doi:10.4088/JCP.13m08896

Paige E, Korda R, Kemp-casey A, Rodgers B, Dobbins T, Banks E.A record linkage study of antidepressant medication use and weight change in Australian adults.Aust N Z J Psychiatry. 2015;49(11):1029-39. doi:10.1177/0004867415607365

Al-harbi.Treatment-resistant depression: therapeutic trends, challenges, and future directions.PPA. Published online May 2012:369. doi:10.2147/PPA.S29716

Fabbri C, Corponi F, Souery D, et al.The genetics of treatment-resistant depression: a critical review and future perspectives.International Journal of Neuropsychopharmacology. 2019;22(2):93-104. doi:10.1093/ijnp/pyy024

Pan LA, Martin P, Zimmer T, et al.Neurometabolic disorders: Potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behavior.Am J Psychiatry. 2017;174(1):42-50. doi:10.1176/appi.ajp.2016.15111500

Li J-M, Zhang Y, Su W-J, et al.Cognitive behavioral therapy for treatment-resistant depression: A systematic review and meta-analysis.Psychiatry Research. 2018;268:243-250. doi:10.1016/j.psychres.2018.07.020

Kellner CH, Greenberg RM, Murrough JW, Bryson EO, Briggs MC, Pasculli RM.Ect in treatment-resistant depression.AJP. 2012;169(12):1238-1244. doi:10.1176/appi.ajp.2012.12050648

Daly EJ, Trivedi MH, Janik A, et al.Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial.JAMA Psychiatry. 2019;76(9):893. doi:10.1001/jamapsychiatry.2019.1189

Centers for Disease Control and Prevention.Mental health conditions: Depression and anxiety.

Barnard K, Peveler RC, Hold, RIG.Antidepressant medication as a risk factor for tye 2 diabetes and impaired glucose regulation: Systematic review.Diabetes Care. 2013; 36(10): 3337–3345. doi:10.2337/dc13-0560

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Antidepressants and Your Brain#

Long-Term Side Effects#

What It Means for You#

Can Antidepressants Stop Working?#

How to Manage Long-Term Antidepressant Use#

The Takeaway#