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13 Signs Your Antidepressant Isn't Working

Kristin Hall, FNP

Reviewed by Kristin Hall, FNP

Written by Nicholas Gibson

Published 10/05/2021

Updated 10/07/2021

Depression is one of the most common mental illnesses. Below, we’ve explained what antidepressants are, how they work and shared some of the most common types of antidepressants used to manage anxiety and depression.

We’ve also shared 13 signs that your antidepressant isn’t working at all, or just isn’t working like it should to treat your depression, anxiety or other mental health issues. 

In fact, the World Health Organization estimates that around five percent of the entire global adult population is affected by some form of depressive illness.

If you’re one of the tens of millions of Americans affected by depression every year, medications such as antidepressants can be a valuable lifeline.

Antidepressants work by changing the levels of certain chemicals, called neurotransmitters, that are present in your brain and body. 

They can produce real improvements for people with anxiety or depression, but they aren’t always effective for everyone. 

In fact, it’s normal for people with depression or anxiety to use several different antidepressants before finding the medication that works best for them. 

If your antidepressant isn’t working, it’s important that you let your healthcare provider know as soon as you can. 

Antidepressants are medications used to treat depression. They work by increasing the levels of certain neurotransmitters in your brain and body, including neurotransmitters that are involved in controlling your moods, thoughts and feelings.

Although antidepressants are mostly associated with the treatment of depression, they’re widely used to treat other mental illnesses. 

Your healthcare provider may prescribe antidepressants to treat anxiety disorders, chronic pain conditions, eating disorders and even certain forms of addiction.

Several different types of antidepressants are prescribed by mental health providers. Based on your symptoms, needs and previous use of medication, your healthcare provider may prescribe one of the following antidepressants: 

  • Selective serotonin reuptake inhibitors (SSRIs). SSRIs are common medications for depression. They work by increasing the amount of serotonin in your brain and are often used as a first-line depression treatment.Compared to older antidepressants, most SSRIs are less likely to cause side effects and drug interactions.

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs). SNRIs work by increasing the amount of serotonin and norepinephrine in your brain. SNRIs are also widely used as a treatment for depression.

  • Tricyclic antidepressants (TCAs). TCAs are an older class of antidepressants. They’re equally as effective as SSRIs, but are typically used less often due to their increased risk of causing side effects.

  • Monoamine oxidase inhibitors (MAOIs). MAOIs are an older class of antidepressants that have been in use for decades. They’re often effective, but have a higher risk of drug interactions than newer antidepressants. MAOIs are sometimes used to treat treatment-resistant depression that doesn’t improve with other medications.

  • Other antidepressants. Some medications used to treat depression are referred to as “atypical” antidepressants. These may be used when other medications aren’t effective, or if conventional antidepressants cause side effects or drug interactions. 

Our full list of antidepressants provides more information about the categories above and lists a range of commonly used SSRIs, SNRIs, TCAs and other antidepressants. 

Research shows that antidepressants increase the number of people who notice improvements in their depression symptoms over time.

However, not everyone who uses antidepressants experiences improvements. Research on the efficacy of antidepressants has found that 20 percent to 40 percent of people with depression will notice improvements naturally over the course of six to eight weeks.

In comparison, 40 percent to 60 percent of people who use antidepressants report improvements in their symptoms over the same time period.

In other words, antidepressants can significantly increase the number of people who feel better, but not by 100 percent. 

While this may not sound ideal, the good news is that it’s often possible to improve your results from antidepressants by switching medications, adjusting your dosage or making other changes to the way you use your medication. 

Look for the following signs that your antidepressant may not be fully effective at improving your depression symptoms

You Still Feel Depressed or Anxious After Several Months

Antidepressants are usually effective, but their effects aren’t immediate. It generally takes a few weeks for antidepressants to begin working, and you may notice improvements to your sleep or appetite before you experience any changes to your moods. 

If you haven’t noticed any improvements after using an antidepressant for two months or longer, it may be a sign that your medication isn’t right for you, or that you need to adjust your dosage.

Your healthcare provider may switch you to a different type of medication or adjust your dosage to provide better results. 

Make sure not to make any changes to your medication without talking to your healthcare provider first. 

You Feel Better Immediately

While this may sound strange, if you feel better as soon as you start using an antidepressant, it could be a sign that your medication isn’t working as intended. 

Almost all antidepressants need several weeks to start working. Researchers believe that this is because it takes time for antidepressants to gradually accumulate in certain parts of the plasma membrane of your cells. 

If you feel better the moment you start using an antidepressant, it’s more likely to be the placebo effect than an actual effect of the medication.

Now, this doesn’t mean that your antidepressant won’t ever work — just that it probably isn’t fully working yet. 

Give it a few weeks and see if your improvements continue. If not, you may need to discuss your medication with your healthcare provider. 

You Have Persistent Sexual Side Effects

Sometimes, antidepressants can cause sexual side effects, such as erectile dysfunction (ED), difficulty reaching orgasm or a weaker-than-normal sex drive.

The risk of these side effects varies between antidepressants, with some common medications more likely to cause issues than others. 

Research shows that many commonly used SSRIs, or selective serotonin reuptake inhibitors, can cause sexual side effects in some people.

Sex is an important part of life, and when medication interferes with your ability to have sex, it can have a serious impact on your wellbeing. 

Luckily, not all antidepressants are linked to sexual issues. Some, like bupropion (Wellbutrin®), have even been studied as potential treatments for sexual health issues caused by SSRIs and other antidepressants.

If you experience sexual side effects after starting an antidepressant, it’s a good idea to inform your healthcare provider. 

They may recommend switching to a different type of antidepressant, adjusting your dosage or using additional medication to improve your sexual function. 

Your Feelings Improve, But You Still Have Other Symptoms

Although many people associate depression with a sad, empty mood, most forms of depression actually cause a range of symptoms.

Common symptoms of depression include irritability, a reduced level of interest in your hobbies, slow movement and speech, difficulty concentrating and remembering things, and even weight loss or gain.

Sometimes, you may notice your moods and feelings improving after you start treatment with an antidepressant, but still have other persistent depression or anxiety symptoms.

This could signal that your antidepressant isn’t quite right for you, or that you may need to adjust your dosage of medication. 

As always, make sure to talk to your healthcare provider before you make any changes to the way you use your antidepressant. 

Your Other Symptoms Improve, But Not Your Mood

On the other hand, sometimes you may notice your physical symptoms getting better after you start taking an antidepressant, all with few or no improvements to your mood. 

This is common during the first few weeks of using an antidepressant. Many people notice that their appetite, sleep and ability to concentrate get better before their moods and feelings slowly begin to improve.

As such, it’s best not to panic if you notice this issue early in your treatment. However, if you’ve taken an antidepressant for several months and still don’t feel any better despite improvements in your physical health, it’s best to let your healthcare provider know. 

You Find it Difficult to Fall Asleep or Stay Asleep

Some antidepressants are associated with insomnia, meaning they may make it harder for you to fall asleep, stay asleep or wake up at a normal time.

For example, antidepressants that have activating effects like fluoxetine (sold as Prozac®) and venlafaxine (sold as Effexor®) are associated with sleep disruption. 

Other antidepressants are linked to lower sleep quality, meaning they may affect how rested you feel after sleeping.

If an antidepressant improves your depression or anxiety symptoms but hurts your ability to fall and stay asleep, it may not be the best choice for you.

It’s worth noting that sleep difficulties are a common symptom of depression and many anxiety disorders, meaning this issue isn’t always caused by medication. 

You’re Constantly Tired and Need to Sleep

While some antidepressants can prevent you from falling or staying asleep, others may cause you to feel drowsy and ready to sleep all the time.

In a meta-analysis published in the Journal of Clinical Psychopharmacology in 2015, a team of researchers looked at the side effects associated with a range of different antidepressants.

They found that eleven antidepressants were associated with somnolence, or a state of feeling drowsy and ready to sleep. 

Other reports have highlighted the medications doxepin, trazodone and mirtazapine as antidepressants that may induce sleep.

This side effect can be both an annoyance and a serious safety risk, especially if you work in an environment in which injury is possible or need to drive after taking your antidepressant. 

If you feel tired, fatigued or simply unable to concentrate after using your medication, it could be a sign that a different antidepressant is a better choice for you. 

Your Antidepressant Feels Less Effective

Sometimes, an antidepressant works well at first, but over time it may become less effective at controlling your depression or anxiety symptoms.

This issue is referred to as antidepressant tachyphylaxis. It happens when your response to an antidepressant gradually declines over time, all without changes to your dosage or the way you use your medication.

Antidepressant tachyphylaxis can be quite common. 

In fact, some research has found that more than 30 percent of people who use certain SSRIs experience a recurrence of symptoms under regular long-term use.

It’s worth noting that the study referenced only involved 77 patients, and the antidepressant they took was fluoxetine, the generic version of Prozac. 

Researchers found a recurrence of symptoms in 33.7 percent of patients between 14 and 54 weeks of use.

Other research found that the number varies widely. One meta-analysis of data found that rates of tachyphylaxis varied anywhere from nine percent to over 50 percent, depending on things like the duration of use and sample size.

Like with other antidepressant problems, it’s important to talk to your healthcare provider if you start to notice your depression or anxiety symptoms returning.

They may switch you to a different antidepressant, increase your dosage or recommend other changes to prevent your depression or anxiety from coming back. 

You Have Other Unwanted Side Effects

Sexual dysfunction, insomnia and somnolence are some of the most well-known negative side effects of antidepressants. However, they’re not the only issues you may experience. 

Other adverse effects of antidepressants include nausea, sweating, dry mouth, weight changes and even flu-like symptoms. 

While side effects don’t necessarily mean that your antidepressant isn’t working, they can serve as a warning sign that it might not be the right medication for you, especially if they’re severe or persistent. 

As always, if you experience side effects from your antidepressant, the best approach is to bring them up with your healthcare provider. 

You’re Experiencing Drug Interactions

Antidepressants can interact with other medications, including some medications available over the counter. 

Some of these interactions may be harmful and even life-threatening. For example, when some antidepressants are taken at the same time as medications that increase serotonin levels, they can result in a group of severe, potentially deadly symptoms called serotonin syndrome.

Drug interactions are a particular risk with older antidepressants, such as MAOIs, which stay in the bloodstream for a long time.

Some antidepressants can even cause severe interactions when used with health supplements like St. John’s wort.

If you’re worried about potential drug interactions, or if you think you might have experienced an interaction from your antidepressant, it’s important to alert your healthcare provider. 

You Forget to Take Your Medication

Even when an antidepressant is effective at treating your depression or anxiety, it might not be the right medication for you. 

Most antidepressants need to be taken daily in order to be effective. If you often forget to take your medication, or if you skip it because of side effects or interactions, it may not be the best treatment option for you. 

If this happens to you, it’s always best to talk to your healthcare provider and find a medication that you can use on a regular, ongoing basis. 

You Feel High After Taking Antidepressants

Antidepressants work by making you feel better at the chemical level. This is great if you have depression, but it can be a major source of frustration, confusion and mood swings if you have bipolar disorder.

Bipolar disorder is often misdiagnosed, usually as depression. In fact, studies have found that almost 40 percent of people affected by bipolar disorder are misdiagnosed with different forms of depression.

If you have bipolar disorder and mistakenly receive antidepressants, you might notice that you feel unusually elated or overjoyed. You may also notice other unusual changes in your moods and feelings.

These may not just be signs that your antidepressant isn’t working — they could also be signs that you’ve been diagnosed with the wrong mental illness. 

You Feel Severely Depressed or Suicidal

Although rare, some antidepressants are associated with an elevated risk of suicidal thoughts and behavior, particularly in children, adolescents and young adults.

Because of this, all antidepressants carry a black box warning from the Food and Drug Administration (FDA) that’s designed to inform users about these risks.

If you feel severely depressed after taking an antidepressant, or if you start to develop suicidal thoughts or feelings, it’s important that you contact your healthcare provider immediately or call 9/11 for emergency care. 

First of all, don’t panic. If your depression symptoms don’t get better with one antidepressant, that doesn’t mean that they’re untreatable. In fact, it’s common to try several antidepressants before finding one that’s a good match for you. 

If you’re experiencing unpleasant side effects from your antidepressant, it’s important that you inform your healthcare provider as soon as possible.

Let your healthcare provider know about what you’re experiencing, as well as how severe the side effects are. 

Make sure to tell them if you’re taking any other medications or supplements that could interact with your antidepressants. 

If your antidepressants aren’t effective, make sure not to increase your dosage or stop taking them on your own.

This may increase your risk of experiencing side effects or antidepressant discontinuation syndrome (a collection of withdrawal-related symptoms).

Based on your symptoms, needs and other factors, your healthcare provider may switch you from your current antidepressant medication to a different one, adjust your dosage or provide you with additional medication to take with your antidepressant.

It might take several tries before you find the right antidepressant for your needs. Understand that treating depression is a process, and finding the right antidepressant is an important step towards overcoming your symptoms and improving your quality of life.

Although antidepressants are effective for most people with depression, finding the medication that best suits your needs can involve some trial and error.

If you notice any of the signs mentioned above, it’s best to let your mental health provider know so that they can recommend suitable adjustments.

This could mean switching medications, adjusting your dosage or using another medication with your antidepressant. 

If you feel depressed and want help, it’s important to talk to a professional. You can connect with a licensed provider from home using our online mental health services and receive personalized care, including therapy and, if appropriate, medication management.

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Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references.

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This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.

Kristin Hall, FNP

Kristin Hall is a board-certified Family Nurse Practitioner with decades of experience in clinical practice and leadership. 

She has an extensive background in Family Medicine as both a front-line healthcare provider and clinical leader through her work as a primary care provider, retail health clinician and as Principal Investigator with the NIH

Certified through the American Nurses Credentialing Center, she brings her expertise in Family Medicine into your home by helping people improve their health and actively participate in their own healthcare. 

Kristin is a St. Louis native and earned her master’s degree in Nursing from St. Louis University, and is also a member of the American Academy of Nurse Practitioners. You can find Kristin on LinkedIn for more information.

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