Long-Term Effects of Antidepressants

What are the risks?

Side effects
Verywell / JR Bee

Antidepressants are among the most commonly prescribed medications in the United States, and they're often prescribed for long-term use. However, there are potential long-term effects of antidepressants on the brain and body, which may include emotional numbness, sexual problems, weight gain, reduced positive feelings, and/or suicidal thoughts.

While this class of medications is named after a single condition, the drugs are used to treat a wide variety of illnesses other than major depressive disorder, including:

  • Binge eating disorder
  • Bipolar disorders
  • Bulimia
  • Childhood bedwetting
  • Fibromyalgia
  • Generalized anxiety disorder and social anxiety disorder
  • Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
  • Neuropathy (pain from damaged nerves, including diabetic neuropathy)
  • Obsessive-compulsive disorder (OCD)
  • Post-traumatic stress disorder (PTSD)
  • Premenstrual syndrome (PMS)

In spite of how popular these drugs are, we're just learning what those long-term effects may be. Extended studies are rarely done before a drug gains approval for use, so medications can be around for a long time before we start to get a clear picture of what can happen after years of continuous use.

Fortunately, the body of literature on the long-term use of antidepressants is growing, and we're gaining a better understanding of their impact on us.

Antidepressants and Your Brain

Before delving into the research, let's look at how antidepressants work. Antidepressants come in several forms. The major ones are:

  • Monoamine oxidase inhibitors (MAOIs)
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Tricyclics (TCAs)

In your brain, information—including emotion—moves from one neuron (brain cell) to another via chemical messengers called neurotransmitters. Think of neurotransmitters as mailbox keys. Each one unlocks certain receptors (chemical "locks") on neurons in order to allow the message to keep traveling.

With many of these conditions or diseases, something is wrong with the brain's neurotransmitters (usually serotonin, 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.

Antidepressants change how neurotransmitters function, making more available so that when a message comes along, it can be properly delivered. This is achieved by slowing down a process called reuptake, which is essentially a clean-up or recycling process.

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.

Side Effects

However, the brain is a complex environment. Each neurotransmitter has a lot of 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 antidepressants are many, and they can range from mildly annoying to debilitating and 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, some of the top concerns that have emerged have to do with weight gain and diabetes. However, many other side effects can continue long term and can have a negative impact on your quality of life.

Long-Term Effects of Antidepressants

In 2016, the medical journal Patient Preference and Adherence published a paper looking at what people taking antidepressants long-term had to say about the side effects that they've seen.

Overall, they did say 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 they complained about included:

  • Sexual problems (72%), including the inability to reach orgasm (65%)
  • Weight gain (65%)
  • Feeling emotionally numb (65%)
  • Not feeling like themselves (54%)
  • Reduced positive feelings (46%)
  • Feeling as if they're addicted (43%)
  • Caring less about other people (36%)
  • Feeling suicidal (36%)

Many of the participants wanted more information about the long-term risks of their medication. About 74% of people also mentioned withdrawal symptoms and 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.

You should 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 an antidepressant, make sure you're familiar with the possible side effects as well as the proper method of going off of them. 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

Weight gain is one of the potential long-term effects of antidepressants on the body.

A 2015 study published in The Journal of Clinical Psychiatry suggests the long-term risk of weight gain from 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.

What It Means for You

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.

Blood Sugar & Diabetes

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 journal Diabetes Care examined 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:

  • Antidepressants may worsen blood sugar control because they can cause significant weight gain.
  • SSRIs and Pamelor (nortriptyline) reportedly worsen blood sugar control in people with diabetes.
  • Tricyclic antidepressants cause hyperglycemia (high blood sugar levels) in humans.
  • In mice, tricyclic antidepressants cause a condition called hyperinsulinemia, in which the blood contains too much insulin relative to the amount of sugar.

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.

What It Means for You

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 your antidepressant is no longer working as 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:

  • Age
  • Alcohol or drug misuse
  • Alternative or cooccurring mental health diagnosis
  • Drug interactions
  • Stress

What It Means for You

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

  • Increasing your dose
  • Adding another medication
  • Switching to a different class of antidepressant
  • Adding psychotherapy or counseling to your treatment plan
  • Making lifestyle changes to help ease depression symptoms

Treatment-Resistant Depression

Roughly 10% to 30% of people don't respond to antidepressant treatments at all, which may be caused by treatment-resistant depression (TRD). Although there is not a standard definition, TRD is often defined as failing to respond to two or more treatment attempts despite adequate dose, duration, and adherence. TRD can lead to poor social functioning, medical comorbidity, and increased mortality.

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

What It Means for You

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:

  • Experiencing a loss of interest in activities
  • Feeling sad or anxious
  • Having suicidal thoughts
  • Sleeping too much or too little
  • Withdrawing from family or friends

If you are having suicidal thoughts, contact the National Suicide Prevention Lifeline at 988 for 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 our National Helpline Database.

A Word From Verywell

As all drugs do, antidepressants have lists of potential pros and cons. Treatment is a balancing act, with you and your doctor(s) weighing the good against the bad and deciding what the next move should be.

Starting a new drug is a big decision, and so is continuing treatment long-term or opting to discontinue. Make sure you're well informed at every step and getting professional advice. In the end, it's all about making you feel better.

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Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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Additional Reading

By Adrienne Dellwo
Adrienne Dellwo is an experienced journalist who was diagnosed with fibromyalgia and has written extensively on the topic.