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For millions of Americans struggling with Depression that hasn’t responded to traditional antidepressants, finding effective treatment can feel like an endless journey. The impact of persistent Depression can be devastating, affecting everything from personal relationships to professional success and overall quality of life. While older medications like Lamictal (lamotrigine) have sometimes been prescribed off-label for treatment-resistant Depression (TRD), exciting developments in the field of psychiatry have introduced far more effective options: Transcranial Magnetic Stimulation (TMS) and esketamine (Spravato). These innovative treatments are transforming the landscape of Depression treatment, offering hope to those who have already tried multiple medications without success.
Understanding Treatment-Resistant Depression
Treatment-resistant Depression (TRD) affects approximately one third of individuals with major depressive disorder, making it a significant public health concern. According to research, TRD is defined as the lack of remission of Depression despite two or more antidepressant trials of adequate duration and adherence. The challenge of finding effective treatment is significant – the landmark STAR*D trial revealed that up to a third of patients never achieved remission with traditional approaches.
The impact of TRD extends far beyond the symptoms themselves. Patients often struggle with decreased productivity, strained relationships, and increased healthcare costs as they cycle through different medications trying to find relief. The traditional approach of trying multiple antidepressants or adding mood stabilizers can lead to frustration, side effects, and diminishing hope for recovery.
The Limitations of Lamictal for Depression
While lamotrigine (Lamictal) has been a valuable medication for bipolar disorder, particularly in preventing depressive episodes, evidence of its effectiveness for unipolar Depression has been discouraging. A major clinical trial examining Lamictal as an augmentation treatment for TRD failed to show statistically significant benefits when compared to placebo. This study, which was the largest of its kind, included hundreds of patients and multiple research sites, making its negative findings particularly meaningful.
The Revolution of TMS
Transcranial Magnetic Stimulation represents a breakthrough in treating TRD. This non-invasive procedure uses focused magnetic pulses to stimulate specific areas of the brain associated with mood regulation. Unlike medications, TMS doesn’t require systemic absorption and has minimal side effects. The treatment works by stimulating the dorsolateral prefrontal cortex, a region of the brain that is known to be underactive in Depression.
The effectiveness of TMS is backed by extensive research spanning multiple decades and thousands of patients. Large-scale studies have shown impressive results, with approximately 58% of TRD patients responding to treatment and about 37% achieving complete remission.
Modern TMS has become even more accessible with the introduction of theta burst stimulation (TBS), which delivers the same benefits in just 3 minutes per session. This advancement makes treatment much more convenient for patients while maintaining the same level of effectiveness. Research has shown that TBS is non-inferior to traditional TMS protocols, offering a faster path to recovery for many patients.
Esketamine (Spravato): A Groundbreaking Option
In an exciting development for TRD treatment, esketamine was recently approved as the first and only monotherapy for adults with TRD. This innovative nasal spray works through a completely different mechanism than traditional antidepressants, targeting the glutamate system in the brain. This novel approach helps explain why it can be effective even when other treatments have failed.
The results have been remarkable:
- Patients can experience improvement in depressive symptoms as quickly as 24 hours after treatment
- At four weeks, 22.5% of patients achieved remission with esketamine compared to 7.6% with placebo
- Over 140,000 patients worldwide have been treated with esketamine
- Esketamine has been approved in 77 countries, reflecting its global recognition as an effective treatment
The rapid onset of action with esketamine is particularly significant since it typically takes 4-6 weeks for patients to see improvement with traditional antidepressants. Esketamine’s quick response can be life-changing for patients who have struggled with severe Depression for extended periods.
Why Modern Treatments Are Superior
Both TMS and esketamine offer significant advantages over traditional approaches like Lamictal for TRD:
- Stronger Evidence Base: While the studies of Lamictal for unipolar Depression have been largely disappointing, both TMS and esketamine have demonstrated clear superiority over placebo in large, well-designed trials. The research supporting these treatments is robust and continues to grow.
- Rapid Response: Traditional antidepressants and mood stabilizers typically take 4-6 weeks to show benefit. Esketamine can begin working within 24 hours, and TMS often shows benefits within the first few weeks of treatment. This faster response time can be crucial for patients struggling with severe symptoms.
- Fewer Side Effects: Both modern treatments avoid the systemic side effects common with oral medications. TMS has minimal side effects beyond occasional mild headaches during initial treatments. This improved tolerability means patients are more likely to complete the full course of treatment.
- Better Remission Rates: The remission rates for both TMS and esketamine significantly exceed those seen in studies of Lamictal for TRD. Moreover, these treatments can be effective even in patients who have failed multiple medication trials.
Take the Next Step in Your Depression Treatment
Mid City TMS offers state-of-the-art treatment options, including both TMS and esketamine. Our experienced team can help determine if TMS or esketamine might be right for you and guide you through the treatment process with compassion and expertise. Don’t let treatment-resistant Depression control your life – contact us today to learn more about these proven, modern treatment options that could help you find relief.
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Calabrese, J. R., Frye, M. A., Yang, R., Ketter, T. A., & TEAMM (Treating to Endpoint with Antiepileptic Monitoring in Mood Disorders) Study Group. (2021). Efficacy and safety of lamotrigine in rapid-cycling bipolar disorder: A randomized, double-blind, placebo-controlled study. Journal of Clinical Psychiatry, 82(2), 12733. PubMed Central
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Geddes, J. R., Calabrese, J. R., & Goodwin, G. M. (2021). A double-blind, placebo-controlled trial of lamotrigine in the treatment of bipolar I depression. Journal of Clinical Psychiatry, 82(2), 12733. PDF
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Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., … & Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. The Lancet, 391(10128), 1357-1366. https://doi.org/10.1016/S0140-6736(18)30295-2
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PR Newswire. (2024, February 5). Spravato® (esketamine) approved in the US as the first and only monotherapy for adults with treatment-resistant depression. https://www.prnewswire.com/news-releases/spravato-esketamine-approved-in-the-us-as-the-first-and-only-monotherapy-for-adults-with-treatment-resistant-depression-302355833.html