The Best 4 Treatments for Treatment-Resistant Depression

Recognizing that you’re struggling with depression and getting the courage to ask for help is hard enough as is. But what happens when antidepressants and psychotherapy aren’t helping you to find relief? Treatment-resistant depression is frustrating, cruel, heavy, and exhausting. It can make you feel hopeless and like you will never find relief. But trust us when we say that relief is possible. Keep reading to learn about the best treatment options for treatment-resistant depression and see if any might work for you.  

What is treatment-resistant depression?  

Clinical depression, also known as major depressive disorder (MDD), is a serious mood disorder. According to the CDC, 6.7% of the population will experience a depressive episode this year, and 14% will have an episode within their lifetimes.   

Of those diagnosed with MDD, over 40% have symptoms that do not respond to medications. A person may have treatment-resistant depression (TRD) if they have tried at least two different forms of medications with no relief.   

Instead of trying medication after medication with no success, the alternative treatment options below are proven to help people with TRD find relief.   


TMS stands for “transcranial magnetic stimulation”. It was FDA-approved in 2008 as a safe, non-invasive, non-medication treatment for clinical depression. It is used to treat people with mental health conditions that have not seen success with medications and/or antidepressants.   

TMS delivers localized electromagnetic pulses to the prefrontal cortex, which is the area of your brain that regulates mood. These electromagnetic pulses stimulate neurons, which release neurotransmitters and hormones such as serotonin and dopamine. These neurotransmitters work to relieve symptoms of depression. Once these neurons are stimulated by TMS, they continue to release these neurotransmitters for a longer period of time compared to other treatments like antidepressants.  

Learn more about TMS treatment. 

Each TMS treatment lasts about 20-30 minutes. The full course of treatment will generally be five days a week for four to six weeks. Generally, patients will feel just like their normal selves after their treatment sessions.  

TMS has extremely limited side effects, especially when compared to traditional medications and antidepressants, so it is also a treatment option for people who may be suffering from side effects while trying to experience relief from their condition.  

Have questions about TMS? Check out our FAQs or give us a call!


Esketamine is a drug derived from the anesthetic ketamine that has a long history of being used to treat depression. It is a more potent form of ketamine and is fairly new to the market as it became FDA-approved in March 2019.    

Learn more about esketamine.

Esketamine treatments come in the form of a nasal spray, which has a brand name called Spravato. The nasal spray is to be used alongside antidepressants to treat more severe cases of depression that are categorized as treatment-resistant depression (TRD).   

Scientists are still studying the exact mechanism by which depression is relieved. However, research suggests that by blocking the NDMA receptors, esketamine stimulates a rapid increase in glutamate within the brain. This increase in glutamate strengthens and restores the vital neural connections and pathways in the regions of the brain most impaired by depression. As a result, there are positive changes in brain circuit function and improved mood regulation.  

Because esketamine is considered a controlled substance, it must be administered by specially trained medical personnel in a certified clinical setting. Most patients receive it as an outpatient and go home in a couple of hours. A typical course of esketamine treatment consists of twelve sessions over two months.  

Explore the 5 amazing benefits of esketamine.

Ketamine Infusion Therapy  

Ketamine infusion therapy has been shown to help patients who struggle with psychiatric conditions, such as treatment-resistant depression, anxiety disorders, post-traumatic stress disorder (PTSD), bipolar disorder, obsessive-compulsive disorder (OCD), and suicidal ideation. While it has yet to be FDA-approved for treating these conditions, clinical studies show that ketamine infusion therapy can effectively treat MDD and TRD with a success rate as high as 70%.  

Ketamine works similarly at treating depression as esketamine, by blocking NDMA receptors and increasing glutamate levels in the brain. When given in low doses, ketamine infusion therapy can produce rapid and significant improvement in symptoms, often within a few hours.  

Because the ketamine infusion is given intravenously and is considered a controlled substance, it must be administered by specially trained medical personnel in a certified clinical setting. Like with esketamine nasal spray treatments, patients receive ketamine infusion therapy as an outpatient and go home in a couple of hours.  

Learn more about ketamine infusion therapy.


ECT stands for electroconvulsive therapy, and it is more of a last resort when it comes to treating treatment-resistant depression or other severe mood disorders. It is reserved for those who have symptoms that are not responding to other types of procedures, therapy, and medications. ECT is considered the best treatment when depression symptoms are occurring alongside suicidal ideation and/or self-harm.  

Learn more about ECT.

The goal of ECT is to stimulate the area of the brain responsible for creating neurotransmitters. ECT directly targets the source through a direct electrical current, which stimulates the brain and triggers a brief seizure. Directly targeting the source allows for progress in the areas that medication and other alternatives can’t reach.  

ECT treatments are administered in a controlled, outpatient setting. During treatment, an electrical current is applied to the scalp to stimulate the brain and intentionally cause a controlled seizure.   

Unfortunately, due to negative media portrayal, ECT is often viewed as a dangerous, painful, and unsafe procedure. However, that is not true. ECT is a safe treatment. It is endorsed by the National Institute of Mental Health, the American Psychiatric Association, the American Medical Association, and the US Surgeon General. Around 100,000 patients are treated with ECT every year in the United States. Those thousands of patients experience ECT without complications and can find relief from their severe depression.   

ECT treatments are closely monitored by professionals while the patient is under anesthesia. Thanks to the anesthesia, the process is painless. Each step of the process is controlled in a safe and clean hospital environment.    

Have questions about ECT? Check out our FAQs or give us a call!

If you have or believe you have treatment-resistant depression, please do not lose hope. One of these treatment options may help you find the relief you deserve. If you’re interested in learning more about these treatments and seeing if they work for you and your unique needs, call our intake line and schedule a consultation. We will work with you to find not just relief but joy.

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