What Are the Long-Term Effects of Antidepressants?

Long Term effects of antidepressants

Many people struggle with depression and take prescribed medication for it. Learn more about the long-term side effects of antidepressants.

No one is immune from the clutches of depression. For many, a key component in battling depression is prescribed medication. According to the World Health Organization, 5% of the global population is on some form of antidepressants. This number is higher in the United States, with 13.2% of adults using these drugs.

Although antidepressants provide a net positive for individuals struggling with depression, they can pose potential risks. Let’s look at some of the long-term side effects of antidepressants, as well as their effects on the brain.

What Are Antidepressants?

The term antidepressant is tossed around a lot in conversation, even in the mental health profession. But the truth is that antidepressants are a category of drugs that vary widely in what they do, what they help treat and their potential side effects. Antidepressants are used to treat depression, as the name suggests, but they can also be used in the treatment of various other conditions, including:

  • Eating disorders
  • Chronic fatigue syndrome
  • Certain autoimmune disorders
  • Anxiety disorders
  • Nerve pain

Antidepressants generally fall into four categories: monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclics (TCAs).

Types of Antidepressants and Their Effects on the Brain

“Antidepressants” is a broad term and can be broken down into more specific categories:

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin and norepinephrine reuptake inhibitors (SNRIs)
  • Trycylic antidepressants (TCAs)
  • Monoamine oxidase inhibitors (MAOIs)

Brain chemicals known as neurotransmitters act as messengers that send information between neurons (brain cells). The neurotransmitters most commonly linked to depression are dopamine, serotonin and norepinephrine. When these emotion-regulating neurotransmitters fail to carry messages properly, or carry them inefficiently, it can result in depression.

Antidepressants such as SSRIs increase serotonin levels in the brain by blocking the reuptake (reabsorption) of it into the neuron. This results in higher availability of serotonin, which improves the communication between neurons. Some common SSRIs include Zoloft, Lexapro and Prozac.

Just as SSRIs specifically target the neurotransmitter serotonin, SNRIs target both serotonin and norepinephrine.

TCAs and MAOIs are some of the first antidepressants created, and function similarly to the previously mentioned SSRIs. Although still in use, they’ve given way to SSRIs and SNRIs, which are more commonly prescribed today.

Long-Term Side Effects of Antidepressants

The long-term side effects of antidepressants like Zoloft can include weight gain, diabetes and even suicidal ideation.

Weight gain can be brought on by antidepressants altering serotonin receptors. This is especially true for women. Factors such as the medication used, the length of time taken and individual body chemistry can all have an impact on weight gain and, in some cases, weight loss.

Type 2 diabetes and irregular blood sugar regulation can result from long-term antidepressant use. One reason for this is the potential for weight gain. SSRIs can also have a negative impact on blood sugar for those with preexisting diabetes. Additionally, tricyclic antidepressants are known to cause hyperglycemia.

Another possible side effect of using antidepressants is suicidal thoughts and feelings. Young adults under the age of 25 are particularly vulnerable to this, especially within the first weeks of taking the medication.

Do Antidepressants Stop Working?

It’s possible to develop a tolerance to antidepressants over time. The scientific term for this is tachyphylaxis. There’s no final consensus as to why this happens to varying degrees between people, but factors can include age, stress levels, drug interactions and other preexisting mental health conditions.

Medical professionals may mitigate the developed tolerance by altering doses, switching medications or suggesting lifestyle changes.

There are also cases, between 10% and 30%, in which patients are completely resistant to antidepressants altogether. This condition is known as treatment-resistant depression (TRD) and is corrected in much the same way as it is when long-term tolerance is developed.

Professional Help for Depression

Depression is a serious mental health issue, and starting a new medication regiment can cause potential negative effects. If you or someone you know is struggling with depression or medication side effects, please reach out to our compassionate staff, on call 24/7.

According to statistics from the Centers for Disease Control, about 11% of Americans aged 12 or over are currently on antidepressants. These medications are often the first line of treatment for depressive disorders and may also be prescribed for anxiety, trauma-related symptoms and other issues.

While antidepressants can seem like a wonder drug for those who are struggling — and they frequently are — it’s important to understand the benefits and risks of any medication you’re considering taking. So, what are the antidepressant side effects over the long term? Keep reading to learn the answer and find out what it might mean for you.

What Are Some Long-Term Antidepressant Side Effects?

Every medication has side effects, and antidepressants are no different. However, it’s important to understand that the side effects often reported for antidepressants are for the class as a whole. To know what to watch out for, ask your doctor for a list of the possible side effects specific to your medication. Here are a few of the common long-term side effects of antidepressants.

Weight Gain

Traditionally, antidepressants have been known to cause weight gain when taken over time, and around 65% of people taking these medications report weight gain as a side effect. How much weight you put on depends on the medication you’re prescribed, how long you take it and your body’s unique chemistry. Some people may find they don’t gain weight at all while on an antidepressant. In some cases, it may not be a side effect of the drug but instead related to a lifestyle change.

For example, someone with anxiety or depression might struggle to cook for themselves or eat nutritious meals. When the antidepressant starts to control these symptoms, the person may want to eat more and may have more energy and desire to cook. The subsequent weight gain this person might experience, therefore, isn’t caused by the medication itself.

However, some antidepressants can cause weight gain, and it’s something to be aware of. This is because being overweight can increase your risk of other health concerns, such as high blood pressure. If you’re concerned about gaining weight while on an antidepressant, weigh yourself regularly and ask your doctor about strategies to control your weight in a healthy way.


It’s thought there may be a connection between Type 2 diabetes and antidepressants, but the actual link isn’t yet clear. Some researchers believe the effect on Type 2 diabetes is related to the weight gain some people experience while taking antidepressants.

In general, being overweight can mean your blood sugar levels aren’t as controlled as they should be, and this can lead to Type 2 diabetes. Those who are dealing with depression may also be more prone to eating processed convenience foods that are easier to prepare and may not be getting enough daily exercise. These factors can also increase the likelihood of blood sugar control issues and Type 2 diabetes.

In particular, SSRIs and tricyclic antidepressants are linked to higher blood sugar levels. If you have a family history of diabetes or have other risk factors, it’s a good idea to talk to your doctor about whether a different type of antidepressant might be more suitable for you. Your doctor can also give you some tips on managing your blood sugar level through diet and lifestyle changes to help mitigate the possible effects of the medication.

Decreased Antidepressant Effect

Perhaps one of the most important long-term side effects of antidepressants is that they can become less effective over time. This means the dose used at the beginning of your treatment that worked well to control your symptoms may become less effective than it was originally. While it’s sometimes possible to just increase the dosage, this isn’t an option in every case or with every medication.

In some situations, you may have to start over to find a new antidepressant that works to control your symptoms. This can often bring with it an uncomfortable adjustment phase and some uncertainty as you balance controlling your symptoms with watching for side effects or other issues with the new medication.

Decreased efficacy can also be a problem if you don’t recognize that it’s happening. Your symptoms could start to come back slowly, meaning you don’t immediately recognize that it’s a medication issue before things get too severe.

The Bottom Line

If the list above sounds a little scary to you, that’s normal. Although it’s wise to be aware of potential side effects, it’s important to take a step back and look at the bigger picture. Most antidepressants are considered very safe, even for long-term use, and the larger concern for most people is finding an antidepressant that regulates their symptoms well over time. If you’re concerned about antidepressant side effects long-term, talk with your health care team to determine what your risk factors are and what medications or alternative therapies may be available. This can help ensure your symptoms are under control and your risk of long-term side effects is as low as possible.

If you or someone you love is struggling with their mental health, antidepressants can be helpful when prescribed in the right circumstances and with attention to the possible long-term effects. Contact Restore today to learn more about our programs and how we can help.

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