When depression doesn’t improve with regular treatments, it can feel like there are no more options. But there is new hope with the ASCERTAIN-TRD trial. This study compares two promising methods: repetitive transcranial magnetic stimulation (rTMS) and switching antidepressants.

The goal is to find out which one works better for people with treatment-resistant depression. The results of this trial could change how we treat depression. It may finally provide relief for those who have been struggling.

What Is Treatment-Resistant Depression?

Treatment-resistant depression (TRD) happens when someone’s depression doesn’t improve after trying two different antidepressants. Major depressive disorder (MDD) is a common condition. However, for some people, regular treatments just don’t work.

Criteria for TRD

Typically, it’s defined as when a patient has undergone at least two separate trials of antidepressants (with adequate dosages and durations) without experiencing significant relief. It’s not simply a matter of the medication not working right away. Rather, it’s when the depression continues to persist despite appropriate and well-monitored treatment efforts.

Medications like selective serotonin reuptake inhibitors  (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants are usually the first line of defense. Yet, in TRD cases, even after trying these, the person remains in a depressive state. And it’s not just medication. Other treatments, such as psychotherapy, may also be ineffective.

Why Does It Happen?

Depression can have many causes. Genetic, biological, environmental, and psychological factors often shape it. Some people may not respond well to antidepressants because of imbalances in brain chemistry. Others might have conditions like anxiety or chronic pain that make treatment more difficult. These added challenges can make finding the right solution harder. Everyone’s experience with depression is different.

Genetics can influence how people respond to medications. Some may process antidepressants differently, which can affect how well they work. Hormonal imbalances and chronic inflammation might also play a role in treatment-resistant depression. Neurological differences can contribute, too. Additionally, depression is sometimes linked to other conditions like bipolar disorder, making treatment more challenging.

The Impact of Treatment-Resistant Depression

Living with treatment-resistant depression (TRD) can feel overwhelming. Despite trying different treatments, the sadness, fatigue and hopelessness stick around. It’s exhausting to keep pushing through when nothing seems to work. This can leave someone feeling frustrated and lost.

Moreover, TRD can affect daily life and long-term goals. Relationships often suffer as the condition remains untreated. Professional productivity declines. For some, it can even lead to social withdrawal. The risk of suicidal thoughts and behaviors is also notably higher in individuals with TRD, underscoring the importance of finding effective treatment solutions.

Alternative Treatments for TRD

When standard treatments fail, alternative or advanced therapies are considered. One common option is Repetitive Transcranial Magnetic Stimulation (rTMS). This non-invasive treatment uses magnetic fields to stimulate specific areas of the brain associated with mood regulation. rTMS is considered effective for many people with TRD, offering a viable alternative to those who haven’t responded well to medication.

Other treatment options may include electroconvulsive therapy (ECT), ketamine infusions, or psychotherapy approaches like cognitive-behavioral therapy (CBT) tailored for treatment-resistant cases. Some patients also explore holistic or integrative therapies, combining medication with lifestyle adjustments, exercise or mindfulness practices.

The Importance of a Comprehensive Approach

Physicians, psychiatrists, and therapists work together to assess the individual’s history, lifestyle, and treatment response. This is important. TRD is not for all situations. It demands personalization. In addition, the patient needs to maintain open communication with their healthcare providers about their feelings and any side effects they may experience.

What Is Repetitive Transcranial Magnetic Stimulation (rTMS)?

Meanwhile, Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive treatment method used primarily to manage symptoms of depression, particularly in individuals with treatment-resistant depression (TRD).

Unlike traditional treatments like antidepressants, rTMS doesn’t rely on medication. Instead, it uses electromagnetic fields to stimulate specific brain regions associated with mood regulation, primarily the prefrontal cortex.

How Does TMS Work?

rTMS sends short magnetic pulses through a coil placed against the scalp. These pulses are targeted at specific brain regions known to be underactive in individuals with depression.

The magnetic fields generated by the device create small electrical currents that stimulate neural activity. This process is designed to “wake up” areas of the brain responsible for mood control, with the goal of improving mood regulation over time.

Each session typically lasts around 30 to 40 minutes. A full course of treatment usually involves daily sessions over several weeks. Importantly, the procedure is non-invasive, requiring no surgery or anesthesia. Most patients can resume daily activities immediately after each session.

Who Can Benefit From rTMS?

rTMS is often recommended for individuals with depression who have not responded adequately to at least one or two trials of antidepressant medication. It’s particularly beneficial for those with treatment-resistant depression. Those who may have found limited success with standard treatments such as medication and psychotherapy.

Beyond depression, rTMS has been studied for its potential to treat other conditions, including anxiety disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). However, its primary use remains in addressing depression, particularly in patients who haven’t experienced adequate relief through conventional therapies.

Side Effects of rTMS

rTMS side effects are usually mild and easy to handle. The most common one is a mild headache or scalp discomfort during or after treatment, but it goes away quickly. Some people may feel lightheaded or notice tingling in their faces. Serious side effects, like seizures, are very rare. They mostly happen in people with epilepsy or other neurological issues.

What Does the Study Reveal About Treatment-Resistant Depression?

The ASCERTAIN-TRD study  the effectiveness of repetitive transcranial magnetic stimulation (rTMS) compared to using medications like venlafaxine XR or duloxetine.

The goal was to determine which option worked best for people who hadn’t had success with standard antidepressants. This research highlighted the need for better treatments for those who didn’t respond to typical medications. It can help improve care for those facing TRD.

Main Findings: rTMS Outperforms Antidepressant Switching

One of the study’s most notable findings is that rTMS augmentation demonstrated superior results to antidepressant switching. They used the Montgomery-Asberg Depression Rating Scale (MADRS), which measures the severity of depressive symptoms.

With MADRS, the study found that patients receiving rTMS experienced a significant reduction in their depression scores compared to those who switched antidepressants. Specifically, the score change for rTMS was −17.39 compared to −13.22 for switching. This 4.17-point difference on the MADRS scale highlights the greater efficacy of rTMS in reducing depressive symptoms.

Furthermore, although the study was not powered to detect statistically significant differences in response and remission rates, it still provided valuable insights. The estimated number needed to treat (NNT) for response and remission in the rTMS group was 7 and 11, respectively. This suggests that rTMS reduces symptoms and could potentially lead to remission in a notable portion of TRD patients.

In addition to rTMS, the study also found that aripiprazole augmentation outperformed antidepressant switching. Mainly in patient-rated outcomes on the symptoms of depression questionnaire. Aripiprazole resulted in a mean score change of −37.79 compared to −34.45 for antidepressant switching. This indicates that aripiprazole could be another valuable tool in treating TRD, especially from the patients’ perspective.

Clinical Implications of the Study

The study found that rTMS works better than switching antidepressants for people with treatment-resistant depression. This is helpful for doctors who face tough decisions when standard antidepressants don’t work. rTMS showed a bigger reduction in depression symptoms compared to medication changes. It gives patients a non-drug option that targets brain areas tied to mood. This finding could guide more effective treatment choices.

For many people, rTMS offers a hopeful alternative to constantly changing antidepressants. Switching medications can take weeks or even months to work, often causing side effects along the way. rTMS, however, is non-invasive and easier to tolerate. It also has a shorter treatment time. This makes it a more attractive choice for some individuals.

The study also supports using aripiprazole as a helpful addition for treating treatment-resistant depression (TRD). Even though rTMS was more effective overall in the main test, aripiprazole helped improve patients’ feelings. This shows that aripiprazole can be part of a personalized treatment plan. It’s an option worth considering based on patient feedback.

Limitations of the Study

While the study offers valuable insights into the effectiveness of rTMS and aripiprazole augmentation for TRD, it also has certain limitations. First, it was an open-label trial, meaning patients knew about their assigned treatment. This lack of blinding could have influenced the results, as patients’ expectations might have affected their perceived improvement.

The sample size was smaller than expected because of COVID-19 disruptions, especially in the rTMS group. The results might not apply to a wider population, like teenagers or older adults, who were not included in the study.

The study only looked at rTMS and aripiprazole as treatments, compared to switching antidepressants. It didn’t include other options like ECT, ketamine, or accelerated rTMS. Because of this, we don’t know how these treatments compare to the ones in the study. More research is needed to explore these other options.

How Effective Is rTMS Compared to Antidepressant Switching?

For individuals with TRD, treatment options are often limited and can feel overwhelming. Antidepressant switching, where a patient transitions from one medication to another, is a common approach for those not responding to their current medication. However, this method may not always provide the desired results. 

Antidepressant Switching: Pros and Cons

Switching antidepressants is a well-established strategy in psychiatry. When one medication doesn’t work, clinicians may try a different class of antidepressants or adjust the dosage. The goal is to find a better drug with the patient’s brain chemistry. For many individuals, switching to a different antidepressant can lead to significant improvements. However, this process is not always successful.

The downside is that antidepressant switching often involves trial and error. Patients may go through weeks or months of new medications without relief, as antidepressants typically take time to show full effects.

Additionally, side effects from new medications can be problematic. Weight gain, sexual dysfunction, fatigue, and emotional numbness are just a few of the potential downsides of antidepressants, especially during the adjustment period.

How Does the TMS Institute of Arizona Provide Relief for Treatment-Resistant Depression?

The TMS Institute of Arizona helps people with treatment-resistant depression using advanced, non-invasive rTMS therapy. Our team customizes each treatment to target the areas of the brain that need stimulation to relieve depression symptoms.

It’s a safe and effective option for those who haven’t found success with medication. We take a compassionate, patient-first approach to care. Our goal is to help you regain control of your mental health.

Interested in learning more about rTMS? Contact us today to find out how we can help you feel better.

References

Papakostas, G. I., Trivedi, M. H., Shelton, R. C., Iosifescu, D. V., Thase, M. E., Jha, M. K., Mathew, S. J., DeBattista, C., Dokucu, M. E., Brawman-Mintzer, O., Currier, G. W., William Vaughn McCall, Mandana Modirrousta, Macaluso, M., Bystritsky, A., Fidel Vila Rodriguez, Nelson, E. B., Yeung, A. S., Feeney, A., & MacGregor, L. C. (2024). Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02468-x

Note: Always consult with a healthcare professional for any medical concerns discussed in this article.