Depression is one of the most prevalent and debilitating mental health conditions worldwide. And in addition, around 30% of people with depression are resistant to common treatments. Treatment-resistant depression (TRD) affects many people worldwide, in spite of a variety of treatment options, such as psychotherapy, antidepressant drugs, and other interventions.
Because it is so important to find solutions for people who struggle with TRD, researchers have explored alternative and complementary treatments. Two treatments that have gained recognition are Transcranial Magnetic Stimulation (TMS) and Spravato® (esketamine) nasal spray. TMS and esketamine have become known as ground-breaking treatments for major depressive disorder and treatment-resistant depression in recent years. Both therapies have shown promise in offering relief to patients who have not benefited from traditional treatments. But can they work together to provide even better outcomes?
Understanding Treatment-Resistant Depression (TRD)
Before delving into the details of TMS and esketamine, let’s make sure we have a good understanding of treatment-resistant depression (TRD).
Depression that does not get better after two or more adequate antidepressant medication trials is known as treatment-resistant depression. Typically, the initial antidepressant medications prescribed to patients are traditional treatments, such as SSRIs (Selective Serotonin Reuptake Inhibitors) or SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors). While these work for many patients, they do not give the same benefits to people with TRD. This can be incredibly challenging and frustrating, and it’s critical to find an effective treatment for those who struggle with treatment-resistant depression.
Fortunately, as mentioned above two innovative, well-studied alternatives have become available to these patients, and they have been incredibly helpful for many people who struggle with TRD. These treatments are transcranial magnetic stimulation (TMS) and esketamine (Spravato®).
Let’s learn more about these two treatments, how they work individually to improve depression symptoms, and how they can work together for additional benefits.
What is Esketamine (Spravato®) and How Does It Work?
Esketamine, sold as Spravato®, is a form of ketamine, a medication that’s been used safely in hospitals for years, mainly to help people feel no pain during surgery. More recently, both ketamine and esketamine have been studied for something very different: their ability to quickly relieve symptoms of depression, especially in people who haven’t found relief from traditional antidepressants.
Esketamine: The Mechanism of Action
The majority of antidepressants function by altering brain chemicals such as norepinephrine or serotonin. Esketamine, on the other hand, works differently. It increases the release of glutamate (one of the brain’s main chemical messengers), which helps brain cells to communicate more effectively.
This spike in glutamate activity promotes something called synaptic plasticity, or the brain’s capacity to form new connections. This synaptic plasticity is believed to be the main reason why some depressed individuals experience quick improvements in their mood and mental clarity. Synaptic plasticity improves communication in brain areas involved in mood and cognition, so it helps reverse some of the disconnect and sluggishness that can come with depression. This leads to faster relief from symptoms like hopelessness, brain fog, and emotional numbness.
Esketamine’s rapid onset of action, sometimes within hours or days, is one of its key advantages over traditional antidepressants, which may take weeks to show results.
What is TMS (Transcranial Magnetic Stimulation)?
Transcranial Magnetic Stimulation (TMS) is a non-invasive procedure used to treat major depression and other mental health disorders. During this treatment, a medical professional uses magnetic fields to stimulate nerve cells in the brain. In particular, the magnetic fields affect the prefrontal cortex, which plays a critical role in mood regulation. TMS is primarily used to treat patients with treatment-resistant depression when medications have failed.
TMS: The Mechanism of Action
TMS works by delivering electromagnetic pulses to the brain, stimulating specific areas involved in mood regulation. This stimulation can increase neuroplasticity, which helps the brain to form new neural connections and improve communication between brain regions involved in regulating emotions and cognition. Most patients report that their depression symptoms have improved after receiving TMS, which is usually administered in a series of sessions spread out over several weeks.
Esketamine and TMS for Treatment-Resistant Depression
Both esketamine and TMS have been shown to be helpful for patients with treatment-resistant depression.
Esketamine was FDA-approved in 2019 as a nasal spray under the brand name Spravato®. It was designed specifically for people with treatment-resistant depression. Esketamine has been shown in studies and clinical trials to be useful in symptom reduction for patients who have not responded well to conventional medications. And additionally, esketamine helps not only with short-term symptom relief, but it can also support long-term recovery by promoting healthier brain function and reducing the likelihood of future depressive episodes when used as part of a continued treatment plan.
Transcranial magnetic stimulation has also become a popular treatment option for people with TRD. A 2023 study found that TMS has a significant effect on reducing symptoms of depression, with some patients also experiencing long-term relief even after completing their TMS regimen.
But while TMS can be very effective for treatment-resistant depression, it does not work for everyone, and it may be even more effective when used in combination with other treatments, such as esketamine.
Can Esketamine and TMS Work Together for Depression Treatment?
Emerging research suggests that combining TMS with esketamine may enhance the effectiveness of both treatments. This can potentially lead to more rapid and sustained relief for individuals with depression.
Complementary Mechanisms of Action
TMS and esketamine target different mechanisms in the brain, meaning they are complementary treatments. While TMS enhances connectivity between key brain regions involved in mood regulation, esketamine modulates glutamate and promotes the brain to be more receptive to changes by adapting. By combining these two treatments, patients may experience a combined effect that leads to improved outcomes.
Summary: The Benefits of Combining Esketamine and TMS
Key Takeaways
- Esketamine, which resets brain communication through the glutamate system, is a fast-acting treatment for treatment-resistant depression.
- TMS uses magnetic fields to stimulate areas of the brain responsible for mood regulation and can provide long-term benefits.
- According to preliminary research, combining TMS and esketamine may intensify their beneficial effects, resulting in quicker relief and better long-term results.
If you struggle with depression or TRD, it could definitely be beneficial to try treatments like Spravato® and TMS. And at Wilshire Institute, we offer comprehensive evaluations to determine the most appropriate treatment options for you. Our compassionate team, led by Dr. Oana Galicki, is here to support you every step of the way. If you live near Beverly Hills, CA, and you or someone you love is struggling with depression, don’t hesitate to reach out and discuss how we can help in your mental health journey.
