Long-Term Effects of Antidepressants

The long-term side effects of antidepressants such 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 use when 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:

• 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)

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:

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

In the 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") that keep the message 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.

Zoloft and other 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.

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 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 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 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 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:

• 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.

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

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

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.

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:

• Prescribe a different antidepressant in the same class
• Change to another type of antidepressant
• Add a second medication, known as augmentation
• Cognitive behavioral therapy (CBT)
• Electroconvulsive therapy (ECT)
• Ketamine
• Repetitive transcranial magnetic stimulation (rTMS)
• Spravato (esketamine) nasal spray
• Vagus nerve stimulation (VNS)

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.

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

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.