Why Are My Antidepressants Not Working?

If you’ve been taking an antidepressant for years and it suddenly feels like it has stopped working, know that this is actually pretty common.

For example, maybe several years ago you talked to your doctor about symptoms like low mood, loss of interest in things they once enjoyed, and fatigue. They diagnosed you with depression and had you start taking Prozac, and you started feeling better. It’s been a few years and you haven’t changed your dose or how you take your antidepressant, yet you’re starting to feel low again. 

Antidepressants like Prozac can help people living with depression manage their symptoms, but they’re not a miracle cure or even a permanent fix. It’s possible for an antidepressant to stop working. In fact, one study found that the rate of depression relapse while taking an antidepressant is about 23% within two years.

There are a lot of things that can affect how well your antidepressant works, such as other medications or supplements you might be taking, using alcohol or other substances, chronic health conditions, and even stress.

In this article, we’ll cover the steps you should take if you think your antidepressant has stopped working, and the reasons why this can happen. 

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Why Do Antidepressants Stop Working? 

Even if you can clearly feel the effects, you won’t be able to know for sure why your antidepressant seems to have stopped working. You’ll need to talk to your doctor or mental health care provider to figure out what’s going on and find a solution. 

In general, though, here are a few of the most common reasons why antidepressants lose effectiveness. 

You Started a New Medication

Medications that you might be taking for another reason can interact with your antidepressant. Your other meds can also cause side effects that could make it seem like your antidepressant isn’t helping. 

For example, let’s say you have inflammation and your doctor prescribes a course of steroids like prednisone. Irritability and mood swings are actually very well-known side effects of steroids, and feeling this way can make you think your antidepressant isn’t helping with your symptoms anymore.

Some medications are processed by your body along the same pathways as antidepressants, so they can actually change how your antidepressant works. For example, some common antibiotics prescribed to clear up infections can increase or decrease how much of your antidepressant is in your bloodstream, which affects how well it works.  

It’s not just prescription medications you have to watch out for—even over-the-counter (OTC) medications, vitamins, and supplements can interact with antidepressants. 

In some cases, these interactions are actually dangerous. One of the most serious examples is taking a supplement called St John’s Wort while you’re taking an antidepressant, which can lead to a serious condition called serotonin syndrome.

What to Do

The providers involved in your care need to know about all the medications you are taking, including prescription, OTC, vitamins, and supplements. They can check for possible interactions and make sure that the antidepressant you’re taking and the dose is safe and effective. 

Your Meds Were Stored Wrong

Medications like antidepressants do best when they’re stored properly, which means keeping them away from moisture, direct sunlight, and big temperature swings. Storing your medication properly helps prevent it from breaking down and losing its effectiveness.

If you’ve noticed you don’t feel like your antidepressant is doing its job, check your storage setup and think back to when you got your latest prescription filled.

For example, you picked up your medication and accidentally left it in your car for a few days in the midsummer heat or a mail-order delivery sat on your porch in a blizzard. With either oops, the extreme temps could have affected your pills. 

What to Do

Check the package insert that comes with your meds or ask your pharmacist about how to store them. Usually, the best choice is to keep the pills in the container they came in and store them in a cool, dark place like a cabinet—and not one in your bathroom that gets steamy when you take a shower, or on a kitchen shelf near your stove that will get hot.

You’re Using Substances

People with mental health conditions like depression may also use substances like nicotine and alcohol. Tobacco smoke and alcohol can affect how your body breaks down and metabolizes your antidepressant. In fact, the way that alcohol interacts with certain antidepressants can be life-threatening. For example, drinking alcohol while you’re taking a monoamine oxidase inhibitor (MAOI) can cause your blood pressure to rise too high and may even lead to a stroke. 

If alcohol and antidepressants are combined, your liver may not be able to process toxins as it should. If the toxins build up in your body, the effects can even be fatal.

What to Do

If you are using alcohol, nicotine, or any illicit substance, be honest with your healthcare provider. They need this info to keep you safe when prescribing medications and recommending treatments that can help you.

You Have Another Medical Condition

Depression is common in people living with chronic medical conditions and in some cases, it can even be a sign of them (for example, thyroid disease). 

Underlying health conditions can also make depression harder to treat. An antidepressant that worked well for you when you were coping with a chronic illness may not be the right fit when you’re trying to deal with the physical and emotional reality of a chronic illness diagnosis.  

Depression is common in people living with diabetes, Alzheimer’s, dementia, Parkinson’s disease, cancer, hepatitis C, and multiple sclerosis (MS).

What To Do

Talk to your providers about your current antidepressant plan and see if you might need to adjust or change it now that you’ll be managing another chronic condition. 

You're Pregnant

There’s a lot going on in your body during pregnancy—from emotional ups and downs and hormonal swings to actual physical shifts in your body. If you feel like your antidepressant is not working while you’re pregnant, these factors could be at play and you might need to adjust your dose.

What To Do

If you’re pregnant or trying to get pregnant, talk to your provider about your depression treatment plan. Some antidepressants are safer to take than others during pregnancy.

You’re Under More Stress

Work pressure? Family challenges? Big changes in your daily life like a move or a new job? Not the time you want to feel like your antidepressant isn’t up to the task of helping your brain stay on an even keel. 

Any new or increased stress can alter your brain chemistry enough to counteract the effects of your antidepressant. You may have breakthrough symptoms of depression during these times and need more support.

What To Do

If you’re going through a really stressful time, reaching out for support from loved ones and a professional can help you cope. Your provider can also review your antidepressant routine with you and see if you need an adjustment. 

You're Getting Older

Changes in your metabolism and body composition as you get older affect how well medications are absorbed, metabolized, distributed, and removed from your body—all of which can change the effectiveness of the medication.

For example, your digestive system gets slower with age which can delay the action of a medication. Your liver can also have a harder time breaking down medications as you get older. 

Sometimes, age-related changes to antidepressants are actually related more to the other age-related changes you’re going through. Maybe you've developed a chronic health condition that you need to take medication for that, in turn, is affecting how your antidepressant works. 

What To Do

Talk with your provider about the pros and cons of taking antidepressants at your age and as you get older. You may want to try other treatments like cognitive behavioral therapy (CBT) along with your meds to help balance out any changes you're experiencing.

You Actually Have Bipolar Disorder

Sometimes, an antidepressant that seems less effective is actually related to the cyclic mood changes that people living with bipolar disorder experience. For people living with bipolar disorder, an antidepressant can actually bring on mania and make their symptoms worse.

What To Do

If you experience mania or hypomania, tell your doctor. It’s possible that you were misdiagnosed with major depressive disorder when you actually have bipolar disorder. 

If you do have bipolar disorder, your provider might want to prescribe a mood stabilizer or antipsychotic medication in addition to your antidepressant to help manage your symptoms. 

You’ve Built Up a Tolerance

When medication no longer works as well for you as it did when you first started taking it, providers use the word “tolerance” to describe what’s happening (the medical word for it is tachyphylaxis).

It’s not just Prozac (fluoxetine), though: “poop out” can happen with any selective serotonin reuptake inhibitor (SSRI). Studies suggest that around 25% of people taking an SSRI will notice a decrease in effectiveness over time.

No one knows for sure why these medications lose their effectiveness the longer you take them, but one theory is that the receptors in the brain become less sensitive to the medication. 

Other common SSRIs prescribed for depression that can “poop out” on you include:

• Celexa (citalopram)
• Lexapro (escitalopram)
• Paxil (paroxetine)
• Zoloft (sertraline)

What To Do

If you've built up a tolerance to the SSRI you’ve been on for a long time, your doctor may suggest changing your prescription (such as increasing the dose), adding another medication (like buspirone), switching you to a different class of antidepressant, starting psychotherapy or counseling as part of your treatment plan, and/or making lifestyle changes.

You’re Having Delayed Effects

It's not uncommon for an antidepressant to make you feel worse before it helps you feel better.

If you just started taking an antidepressant, it's possible that its effects will take a few weeks to kick in. You might feel worse at first because you’re adjusting to side effects like anxiety, fatigue, nausea, or weight gain. 

What To Do

Some of these side effects will go away on their own, but you still want to tell your doctor if you’re having them. Depending on the severity of the side effects, they may want to change dosage and/or medication type, or they may keep an eye on you over the course of a few weeks to see if you start feeling better or not.

How It Feels When Your Antidepressant Stops Working

How do you know your antidepressant isn't working anymore? There are some signs that can clue you in that your antidepressant is no longer helping, but how you feel will depend on the condition the medication was meant to treat. 

If you're having a depression relapse, it's likely that your medication is no longer effective. Depression relapse is when you’ve been managing well with an antidepressant only to start having symptoms like feeling sad, irritable, anxious, or having thoughts of self-harm again.

If your antidepressant is not working for anxiety, you might notice your symptoms have gone back to what they were before you started medication—or they can even feel worse than before.

Many providers consider SSRIs the most effective antidepressants, but that does not mean they work for everyone or work forever. Your provider might want you to try a different kind of antidepressant if an SSRI is no longer helping you, or might want to add another kind of antidepressant to your current one to see if it helps.

The most important thing to remember? If your antidepressant isn't working well anymore, it doesn’t mean it's your fault. Even a mistake like storing your prescription in a not-so-great place is actually really common and it can be easily fixed. But there are also factors out of your control, like medical conditions and aging, that mean the antidepressant you're on just isn't the best fit for you anymore.

Talking to your provider about what you’re going through and how you’re feeling is the first step to coming up with a plan that will help you manage your depression symptoms in the most effective way possible.