What to Do When Antidepressants Don’t Work for You (and Why)

If we were living in a perfect world, antidepressants would start working straight away. But in reality, they can take six to eight weeks to start showing noticeable effects. If you feel your antidepressants aren’t working, it’s important to be patient and give your medication time to work. It’s also completely normal to feel low on some days, even during depression treatment. 

But if you’ve been consistent with your medication and still feel like something isn’t right, it may be a sign that your current treatment isn’t working for you. In this article, we discuss what to do when antidepressants don’t work for you, including signs to look out for, reasons why antidepressants may not work, and what your options are. 

A note of caution

Before we proceed with the rest of the article, we want to make it clear that you should never stop taking your medication or change your dosage without medical guidance. If needed, your medication management provider can safely adjust your treatment and help you explore alternative options. 

Key takeaways: 

• Some signs that your antidepressants might not be working are that your depression feels worse, you’re experiencing mood swings, or have unpleasant side effects. 
• Certain factors can affect how well an antidepressant works, including certain medical conditions, drug or alcohol use, pregnancy and hormonal changes, age, and interactions with other drugs or supplements. 
• Everyone is different, and finding the right medication can take a bit of time. If your antidepressant doesn’t seem to be working, your provider might recommend adjusting the dosage, switching medications, or exploring alternative therapies.  
• Treatment-resistant depression (TRD) is a type of depression that doesn’t respond to traditional treatments like medication or therapy. If you think you have TRD, some treatments to explore include TMS therapy, esketamine nasal spray, or ECT. 

Signs your antidepressants aren’t working

Before we get into what to do, let’s look at some signs that your antidepressant medication might not be working as it should:

Your mood still feels low

If you’ve been taking your antidepressant as prescribed for several months and still feel persistently low, hopeless, or unmotivated, it might mean that the medication isn’t having the desired effect. This could be a sign that it’s time to adjust your treatment plan. 

You feel more energized, but still depressed

Some people might feel a physical boost in energy without any real emotional improvement. In some cases, this could be a cause for concern as increased energy combined with lingering depression may increase the risk of suicidal thoughts or impulsive behavior. If you’re experiencing this, it’s important to speak with your medication management provider as soon as possible. 

You’re experiencing unpleasant side effects

Antidepressants can cause side effects like nausea, weight gain, sexual dysfunction, or insomnia. These side effects can sometimes interfere with daily life and be disruptive or unpleasant, even if your depression symptoms have improved. If you’re experiencing intolerable side effects, it may be worth trying a different medication or dosage. 

You notice signs of serotonin syndrome

In rare cases, taking antidepressants can lead to serotonin syndrome, especially when combined with other medications. This happens when the body accumulates too much serotonin, causing symptoms like: 

• Agitation or restlessness
• Sweating or shivering
• Rapid heartbeat
• Headache or dizziness
• Muscle twitching
• Confusion or disorientation. 

These signs can appear within a few days or weeks of starting a new antidepressant or increasing your dosage. If you notice any of these symptoms, or feel unusual after starting or increasing medication, reach out to your provider immediately. 

Your depression feels worse

Antidepressants should never make your depression worse. If you notice stronger feelings of sadness, hopelessness, disconnection, or any other depressive symptoms after starting medication, talk to your medication management provider right away. This might be a sign that your medication isn’t the right fit. 

You have mood swings

Some antidepressants can cause unexpected mood swings. If you’re feeling more irritable, angry, or even manic, it could be due to the dosage or type of medication you’re taking.  

Why isn’t my antidepressant working?

There are many reasons why an antidepressant might stop working, or never work at all, and most of them are manageable with the right support. 

Here are some common reasons that might affect how well your antidepressant works:

New or increased stress

Big life changes, whether it’s a break up, moving house, losing a job, or caring for a loved one, can put extra strain on your mental health. If your stress levels have increased since starting an antidepressant, your current medication may no longer be strong enough to keep symptoms under control.

Drug or alcohol use

Alcohol, recreational drugs, and sometimes even smoking can interfere with how your body processes antidepressants. They can also intensify mood swings, which can make it hard to tell if your medication is working as it should be. 

Other medications or supplements

Some over-the-counter medications, herbal remedies, and prescription drugs can interact with antidepressants and reduce their effectiveness. Make sure to always tell your provider if you’re taking any other medication, vitamins, or supplements so they can check for any potential drug interactions.  

Medical conditions

Some underlying physical health conditions, like thyroid disease, diabetes, or hormonal imbalances can mimic or worsen symptoms of depression. Being diagnosed with a new medical condition also adds extra stress that worsens depression symptoms. In these cases, it may be necessary to treat the medical condition as well as your depression to see real progress.  

Pregnancy and hormonal changes

Your body goes through many changes when you’re pregnant. Even if your antidepressant is safe to take while pregnant, you may need to adjust the dosage. Hormonal shifts related to menopause or other reproductive changes can also affect how well antidepressants work. 

Drug tolerance (tachyphylaxis)

Sometimes, people who initially responded well to an antidepressant might stop seeing the same results over time. This is known as tachyphylaxis or ‘Prozac poop-out’, and it can especially happen when taking selective serotonin reuptake inhibitors (SSRIs). Researchers aren’t quite sure why this happens yet, but it may be related to changes in brain chemistry over time. 

Age and metabolism

When we age, our body’s ability to metabolize medications can change. This means that antidepressants might be processed differently than before, sometimes requiring a dosage adjustment or switch to another medication. 

Things to try if antidepressants aren’t working

If you’ve tried antidepressants and they haven’t helped, or the benefits haven’t lasted, it’s completely understandable to feel frustrated. But don’t lose hope. Treating depression can take time, and sometimes the first (or even second) medication or dosage isn’t quite right for you. 

Thankfully, you have options, and your care team will help you find what works best for you. If your antidepressant isn’t working, here are a few medication strategies your provider might explore:

Giving it more time

Antidepressants usually take four to eight weeks to become fully effective, and sometimes it can take even longer. If you’ve only recently started your antidepressant treatment, your provider might recommend that you hang in there for a bit longer, especially if you’re beginning to notice even minor changes in mood, sleep, or appetite. 

Adjusting the dosage

Finding the right dosage of an antidepressant can be tricky, but it’s essential to feeling better. Everyone is different, and some people might need higher or lower doses than others to get the full benefit of their medication. Speak to your provider about if this is an option for you – don’t try to make any changes on your own. 

Switching medications

It’s actually quite common for the first antidepressant to be less effective than expected. Your provider might recommend you try a different medication in the same class, or even switching to a new class altogether, to see if it works better with your brain chemistry. 

Combining two antidepressants

In some cases, it’s more effective to take two types of antidepressants together (e.g. an SSRI and an SNRI). This could have a broader effect by targeting different brain chemicals linked to mood regulation, like serotonin, dopamine, and norepinephrine.

Adding a different type of medication

Sometimes, a provider might recommend adding a medication that’s generally used for another physical or mental health condition, like: 

• Antipsychotics
• Mood stabilizers
• Anti-anxiety medications
• Thyroid hormone therapy. 

What to do if depression medication isn’t working

If you think your depression medication isn’t working, the first thing to do is speak to your mental health provider or doctor. Let them know what you’re experiencing, whether it’s a lack of improvement, symptoms returning, unpleasant side effects, or anything else. The more information you share, the better they can help tailor your treatment plan. 

Remember, it’s very common to try multiple medications before finding the right one for you, and the right dosage. Some people might go through three or four prescriptions before they find relief. Everyone’s brain chemistry is different, and finding the right treatment can take time, so it’s important to be patient and have compassion with yourself. 

That said, if you’ve tried two or more antidepressants for a full course of treatment, and still haven’t seen results, you may be experiencing what’s known as treatment-resistant depression (TRD). 

What is treatment-resistant depression?

Treatment-resistant depression (TRD) is a form of major depressive disorder (MDD) that doesn’t improve with standard first-line treatments, like antidepressant medications or talk therapy. You may have TRD if you’ve tried two or more different antidepressants, at the right dose and for an adequate time (usually six to eight weeks), and they didn’t improve depression symptoms. 

This doesn’t mean that your depression is untreatable, it just means that you might need a different approach. Despite its name, TRD is treatable, you may just need to try some alternative therapies to feel relief. 

Ways to treat depression without medication

If antidepressant medications aren’t working for you, here are some alternative ways to manage treatment-resistant depression:

Transcranial magnetic stimulation (TMS) therapy

TMS is a non-invasive, FDA-approved depression treatment that uses gentle magnetic pulses to stimulate nerve cells in regions of the brain linked to mood and emotion. During a TMS session, a small electromagnetic coil is placed on your scalp that delivers focused pulses to help reset your brain’s mood-regulating pathways. 

Sessions usually last about 20 minutes and no anesthesia or sedation is required. Because there’s no downtime, you can drive yourself back home or to work immediately afterwards. A typical course of TMS involves five sessions per week for about six weeks, and most people begin to notice results within a few weeks. It’s a generally well-tolerated treatment with minimal side effects, most of which tend to subside as you progress with treatment. 

Esketamine nasal spray (Spravato®)

Esketamine is an FDA-approved prescription nasal spray approved specifically for adults with treatment-resistant depression. It works differently from traditional antidepressant drugs and can help reduce symptoms in those who haven’t found relief through other medications. 

Spravato® is administered under medical supervision in a clinical setting and patients are monitored for about 2 hours after each treatment. It’s usually given twice a week at first, then gradually tapered. Esketamine must be taken alongside an oral antidepressant, but it can help relieve symptoms in the time it takes for medications to take effect. 

Electroconvulsive therapy (ECT)

ECT is a treatment option for major depression that hasn’t responded to other therapies. It involves using controlled electrical stimulation to trigger brief seizures that can help ‘reset’ certain brain pathways. 

ECT is performed under anesthesia in a hospital setting and is often used in urgent situations, like depression with suicidal thoughts. It is different to TMS and may cause short-term memory loss or confusion, but it can provide significant relief for some patients.  

Vagus nerve stimulation (VNS)

VNS is usually reserved for cases where other treatments (like TMS and ECT) haven’t worked. It involves implanting a small device in the chest that sends electrical signals to the brain via the vagus nerve. VNS is often considered a last-resort treatment for chronic treatment-resistant depression. 

Who to talk to if your antidepressants aren’t working

If you’re taking antidepressants and they’re not helping, or you think you may have treatment-resistant depression, it’s important to know that you’re not alone and support is available. 

At Psychiatry Treatment Centers, we can help you find relief when traditional treatments don’t seem to be working. Our team of mental health professionals work closely with you to adjust your dosage, recommend alternative medications, or explore other options like TMS therapy or Spravato®, both of which are offered at our clinics throughout Georgia and California. 

Reach out to our team today to learn more about your options or book a consultation.