What to Do When Antidepressants Don't Work: Taking Next Steps

by Erika Krull, MSEd, LMHP

Treatment for depression often begins with being prescribed an antidepressant. There are lots of choices for antidepressants, with different classes all designed to work on different neurotransmitters, or chemicals in the brain. Yet despite this variety, about one in three people don't respond to antidepressants.

If you've tried a few different antidepressants but seen no results, you may feel like giving up. But there's always hope for finding a treatment that works. If you're not sure what to do when antidepressants don't work for you, this article will provide an overview of the medication options available, the non-drug treatments for depression, and what to consider when making a change.

Understanding Common Antidepressants

Scientists have designed antidepressants to work with certain neurotransmitters, which are chemicals in the brain that carry messages through your nervous system. Each medication class targets a specific neurotransmitter to help improve your mood.

The most commonly prescribed class is selective serotonin reuptake inhibitors (SSRIs), which work with the neurotransmitter called serotonin. That said, there are several classes that all target slightly different combinations of neurotransmitters. If your antidepressant medication isn't working, your doctor's first step will likely be switching antidepressants to see if targeting a different set of neurotransmitters is more effective.

Another route your doctor may try is prescribing a combination of medications. This may be a good option if you aren't getting enough relief from a single antidepressant, especially if you've been taking it for several months. If you have chronic depression or some severe symptoms, a combination treatment might be helpful for you.

This could mean using two antidepressants at the same time, or you could take an antidepressant along with a different medication. This approach is often called an augmented treatment. As an example, antidepressants can make bipolar depression symptoms worse when used alone, but they're more likely to be effective when paired with a mood stabilizer. Anti-psychotic medication can also be used with antidepressants, and this combination can help some people who see little improvement after trying several treatments.

The use of combination treatments has become more common in the last two decades. A report from 2018 showed that approximately 60% of people who didn't get enough relief with one antidepressant were prescribed a combination of medications. In 1996, more than a million of all people estimated to have depression were using a combination treatment. By 2015, that number had grown to nearly 5 million.

How Many Antidepressants Will You Need to Try?

Some people who try antidepressants get relief on their first try. But those who don't feel better right away may try three or four medications before they find one that works. Some trial and error is common, but it can be a discouraging process.

If you've struggled in your search for an antidepressant that works, you're not alone. The success rate for finding an effective antidepressant on the first try is approximately 70%, meaning about one in three people don't. If you don't feel better after six to eight weeks, you may be asked to try another one. It's important to note that each consecutive change in medication is less likely to work than the one before. That said, many have seen their symptoms improve after trying several types or combinations of antidepressants.

When to Look for Non-Medication Treatments

Although antidepressants are an effective treatment, they do not work for everyone. It may be time for you to start looking into other options when:

  • Your symptoms haven't improved after trying at least two antidepressants, taking each one as prescribed for at least six to eight weeks.
  • You're experiencing side effects that are impacting your weight, sleep, libido, or are otherwise lowering your quality of life.

If either of these factors are the case, you may have treatment-resistant depression (TRD), meaning medication has limited benefits for you. If you suspect you have TRD, switching to a non-medication treatment may be more effective.

Before making changes to your medication, help your doctor understand your symptoms and how you feel. Making a change on your own can be dangerous, so you'll want to schedule an appointment to discuss your options if you're considering stopping or switching antidepressants.

A non-medication treatment like Transcranial Magnetic Stimulation (TMS) may be an option for you. TMS therapy uses magnetic pulses to target specific areas of the brain that regulate emotions. If antidepressants aren't working for you, TMS might be a more effective treatment to diminish your symptoms because it's a non-drug option and does not have drug-related side effects.

Considering a Treatment Change

If you've had trouble finding the right treatment, and you feel stuck wondering what to do when antidepressants don't work, remember you have more options than you might think. It's okay to make a change—you deserve a treatment plan that works for you. If your antidepressants aren't working as well as you'd like, we're here to help.

If Covid-19 and social isolation are heightening your symptoms of depression, Greenbrook TMS therapy may be able to help. At Greenbrook, we specialize in TMS therapy — an FDA-cleared, non-invasive treatment for treatment-resistant depression and OCD without harmful side effects. See if TMS therapy is right for you by clicking here to take a brief assessment:

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