Treatment-Resistant Depression: A Potential Solution

✍️ Alessia Stanistreet-Welsh | MRes Regenerative Medicine Student at the University of Edinburgh

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What is treatment-resistant depression? 🧠

Treatment-resistant depression refers to a condition where antidepressants do not work well enough or not at all

Clinical depression has reached epidemic proportions globally, affecting over 300 million people, or roughly 4% of the world's population. While conventional treatments such as antidepressants have shown success for many, up to 30% of individuals with depression do not respond to such treatment, leading to a condition known as treatment-resistant depression (TRD).

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What causes treatment-resistant depression? ❓

The cause behind treatment-resistant depression remains unclear, but studies have identified several risk factors:

• Genetics - an individual's genetics may make them less likely to respond to antidepressants

• Coexisting Conditions - the prevalence of anxiety and other mental disorders alongside depression may affect treatment outcomes

• Age - older individuals may respond less to treatment

• Severity - severe depression is associated with risk of treatment resistance

• Type of depression - treatment resistance is more prevalent in bipolar depression

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How can we combat treatment-resistant depression? 💭

Transcranial magnetic stimulation (TMS) has emerged as a promising non-invasive therapy for those seeking relief from stubborn hard-to-treat depression symptoms. Developed back in 1985 by Dr Anthony Barker and his colleagues, the technique involves placing magnetic coils on a patient's head, allowing for stimulation of underlying brain regions.

Patient undergoing Transcranial Magnetic Stimulation

TMS is a non-invasive deep brain stimulation technique

This technique is more precise than the traditional method of using direct electrical stimulation via electrodes on the scalp, as well as being far less painful and invasive. However, the potential of using TMS to treat mental health conditions wasn't realised until 2008 when the FDA approved the first TMS therapy for depression. TMS treatment for depression typically involves daily treatments for 4-6 weeks.

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How effective is TMS? 👩‍🔬

Between its development in 1985 and the first FDA approval of the therapy in 2008, extensive studies were conducted to determine the efficacy of TMS as a potential treatment for mental health conditions. Initial studies examined the efficacy of a type of TMS known as repetitive TMS (rTMS), which involves applying recurring TMS pulses to a specific brain region. Studies show that response rates (defined as a 50% decrease in scores on depression scales) of individuals with TRD to rTMS was approximately 40%, with an overall remission rate (defined as a long-term reduction in depression symptoms) of 36%. These results are comparable to those observed with depression medications. However, what truly makes rTMS an attractive treatment option for depression is that the therapy causes fewer side effects than conventional medication. However, some individuals still experience side effects including scalp discomfort and pain, headache, light-headedness, tingling, spasms, or twitching of facial muscles.

40% of individuals with TRD respond to rTMS, and 36% achieve remission of depression symptoms

Further research has been conducted demonstrating the efficacy of another type of TMS known as deep TMS (dTMS). The deep TMS coil stimulates deeper and wider areas of the brain compared to rTMS. Studies show that dTMS improves both depression and anxiety symptoms in patients with TRD, with response rates of 48% and remission rates of 36%. Combination of dTMS with antidepressants produced an even greater improvement of symptoms in those with TRD. Whether TMS can offer long-term treatment for depression is still uncertain, however, a 2018 review reported that up to 50% of people continued to respond to TMS 12 months after their initial treatment.

The FDA approved the first ever TMS therapy for depression in 2008

The promising results of TMS therapy led to the FDA approval of the first-ever TMS treatment for depression in 2008. Approval of TMS for depression in the UK came later in 2015, due to prior concerns over safety and efficacy. This has been followed by further approval of TMS therapies, including those for chronic migraines, obsessive compulsive disorder and major depressive disorder.

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How does TMS Work? 👩‍🔬

While TMS therapies have become more readily available, questions persist about how they actually work to improve depression. The exact mechanisms behind TMS are not fully understood, but it appears to reconfigure brain circuits, resulting in improved communication between different brain areas. Studies show that individuals with depression often exhibit reduced activity in a brain region called the dorso-lateral prefrontal cortex (DLPFC), making it a key target for TMS therapy. By stimulating this region, TMS aims to restore normal activity levels and alleviate symptoms associated with depression.

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Is transcranial magnetic stimulation a beacon of hope for treatment-resistant depression? 🌟

In the face of the global depression epidemic, transcranial magnetic stimulation stands out as a beacon of hope for those who have exhausted traditional treatment options. While questions remain about its mechanisms and long-term effects, TMS has demonstrated significant success in combatting depression, especially in cases where other therapies fall short. Researchers are continuing to refine TMS, with hopes that it can become more accessible and more effective in the future. As the journey of TMS unfolds, it shows promise in reshaping the landscape of mental health treatment, offering new possibilities and new hope for those battling depression.

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Edited by: Olivia Laughton | Content Editor | Microbiology BSc, University of Leeds

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