Cognitive dysfunction is a common, often debilitating symptom of Major Depressive Disorder (MDD). While treatments like repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied individually, the combined approach offers something new. A recent study shows the powerful benefits of using these therapies together to address cognitive impairment.

What Cognitive Issues Are Common in Major Depressive Disorder?

Cognitive issues are a major but often overlooked aspect of Major Depressive Disorder (MDD). While many tend to associate depression primarily with mood symptoms, cognitive dysfunction can be just as disruptive. In fact, cognitive impairment is present in approximately 85% of people with depression, even during periods of remission. These cognitive difficulties affect various mental processes, including memory, attention, and decision-making.

Memory problems are common in MDD. Both working memory (the ability to hold and manipulate information) and episodic memory (recollection of past events) are frequently impaired. People with MDD often struggle with memory recall and may forget everyday tasks. This makes it difficult to retain information, leading to issues at work, school, or in social settings.

Attention and concentration deficits are features of cognitive dysfunction in MDD. Many individuals with MDD experience noticeable difficulties in maintaining focus. This is especially evident during tasks that require sustained concentration. Often referred to as “brain fog,” it leaves thoughts feeling disorganized. As a result, staying focused becomes a challenge. This impaired attention disrupts daily activities, making it hard to manage responsibilities effectively.

Executive function — the cognitive skillset responsible for decision-making, planning, and problem-solving — is also affected by depression. Individuals have a hard time organizing tasks, making informed decisions, and responding appropriately to complex situations. For example, choosing between two options or planning out long-term goals can feel impossible. They may struggle with procrastination, avoid responsibilities, or make impulsive decisions.

In terms of processing speed, MDD often slows down cognitive processing. People with depression can experience a lag in the time it takes to understand and respond to information. A study found that individuals with MDD show slower cognitive processing speeds than healthy individuals. This slowdown affects everything from simple tasks, like reading and writing, to more complex tasks that require quick thinking.

These cognitive challenges are not just present during depressive episodes. Research shows that even when mood symptoms improve, residual cognitive dysfunction persists in 30-50% of MDD patients. This highlights the need for treatment approaches that address both the emotional and cognitive aspects of depression.

Moreover, cognitive dysfunction in MDD has been closely tied to decreased work productivity. Social functioning is also notably impacted. Many individuals feel less capable in their professional roles. Others experience significant strain in personal relationships. These challenges stem directly from cognitive difficulties.

What Is rTMS and How Does It Improve Brain Function?

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique. It’s primarily used to treat depression and other neurological disorders. The process involves applying magnetic pulses to targeted areas of the brain, typically the prefrontal cortex.

These pulses stimulate nerve cells, helping regulate abnormal brain activity. Since its FDA approval in 2008, rTMS has become an important treatment option. It is especially valuable for those who don’t respond to traditional therapies like antidepressants.

How does rTMS improve brain function?

• Targets specific brain regions: rTMS targets the left dorsolateral prefrontal cortex (DLPFC), a region often underactive in individuals with depression. Its role is to regulate mood and make decisions. Stimulating the DLPFC with rTMS helps restore its activity. In turn, this supports the normalization of brain function.
• Increases neural connectivity: rTMS promotes neuroplasticity, which is the brain’s ability to form new neural connections. Enhanced connectivity between brain regions helps improve cognitive function and emotional regulation.
• Improves symptoms in resistant depression: Patients with treatment-resistant depression experience significant symptom relief with rTMS. This is crucial for those who haven’t responded to antidepressant medications.
• Minimal side effects: rTMS does not require anesthesia. It also avoids causing memory loss or seizures. The most common side effects are mild headaches. Scalp discomfort may also occur, but these typically resolve on their own.

What Did the Study Reveal About rTMS and tDCS Combined?

The recent research titled “Cognitive enhancing effect of rTMS combined with tDCS in patients with major depressive disorder: a double-blind, randomized, sham-controlled study” studied the potential benefits of combining repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) for treating cognitive dysfunction in patients with Major Depressive Disorder (MDD). 

How Was the Study Designed?

This study was meticulously designed as a double-blind, randomized, sham-controlled trial, ensuring robust and reliable data. Initially, 550 patients with MDD were screened, and 240 inpatients were selected to participate. These participants were randomly divided into four groups to test various combinations of rTMS and tDCS:

• Active rTMS + Active tDCS
• Active rTMS + Sham tDCS
• Sham rTMS + Active tDCS
• Sham rTMS + Sham tDCS (control group)

A total of 203 patients completed the study, receiving 10 treatment sessions over two weeks. To measure the cognitive and depressive outcomes, the researchers used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to evaluate cognitive function and the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess depressive symptoms.

What Were the Key Findings of the Study?

The combination of rTMS and tDCS demonstrated significantly greater improvements in both cognitive function and depressive symptoms compared to the other groups. Specifically, the study revealed several important findings:

• Cognitive Improvement: The group receiving both active rTMS and active tDCS showed substantial improvements in cognitive function, as measured by the RBANS total score. These patients had significant enhancements in immediate memory and visuospatial/constructional abilities compared to the other groups. Notably, these cognitive improvements were more pronounced in the combined therapy group than in any group receiving only rTMS or tDCS alone.
• Memory and Visuospatial Gains: The combined therapy group demonstrated a significant boost in the RBANS total score, with specific improvements in immediate memory and visuospatial/constructional abilities. Immediate memory improvements, however, were primarily superior compared to the sham group, indicating a unique benefit from the combined approach. This is particularly relevant for MDD patients, as cognitive issues often persist even when mood symptoms are managed.
• Mood and Depression Symptoms: Not only did cognitive function improve, but the combined rTMS and tDCS group also experienced a greater reduction in depressive symptoms, as evidenced by a more substantial decrease in the HDRS-24 total score. This group had a better response rate to depression treatment compared to the other groups, underscoring the dual benefit of this combined approach—targeting both cognitive and mood-related symptoms.

How Does This Compare to rTMS or tDCS Alone?

One of the most notable aspects of this study is the comparison between combined and single treatments. Interestingly, neither rTMS nor tDCS alone resulted in significant cognitive improvements beyond those seen in the control group. This finding suggests that while these treatments can be beneficial individually, their effectiveness is notably enhanced when used together. The combination appears to offer a synergistic effect that neither therapy achieves alone.

• rTMS Alone: Patients receiving only rTMS did show some improvement in the RBANS total score, but these gains were less significant than in the combined therapy group. This suggests that while rTMS can improve cognitive function, it is not as powerful as the combined approach.
• tDCS Alone: Similarly, tDCS on its own did not outperform the sham group in terms of overall cognitive performance, further emphasizing the unique benefits of using both treatments in tandem.

Why Is This Study Important for MDD Treatment?

This study is groundbreaking for several reasons. First, it highlights the need for more comprehensive treatment approaches in MDD, especially for patients suffering from cognitive dysfunction. Moreover, traditional treatments for depression, such as antidepressants and psychotherapy, primarily target mood symptoms but often fail to address the cognitive impairments that significantly reduce quality of life.

• Synergistic Treatment: The combination of rTMS and tDCS offers a synergistic effect, meaning the therapies work together to create an outcome that is greater than the sum of their parts. This is particularly important for MDD patients who struggle with cognitive impairments, as improving cognitive function can also help improve daily functioning and overall quality of life.
• Dual Benefits: The fact that this combined therapy not only improves cognitive function but also reduces depressive symptoms makes it a particularly attractive treatment option. Many MDD patients experience cognitive deficits even after their mood symptoms have been alleviated, and this therapy addresses both aspects of the disorder.

What Are the Safety Considerations?

One important aspect of the study was the emphasis on safety. Both rTMS and tDCS are considered non-invasive and safe treatments, with minimal side effects. In this study, no serious adverse events were reported, further confirming the safety of combining these two therapies. Common side effects included mild headaches and scalp discomfort, but these were temporary and resolved without the need for additional medical intervention.

• Mild Side Effects: The mild side effects observed, such as headaches and scalp irritation, are consistent with those typically associated with rTMS and tDCS. Importantly, these effects were manageable and did not interfere with the completion of the treatment sessions.
• No Serious Adverse Events: The study found no significant adverse events related to the combination of rTMS and tDCS, suggesting that this combined treatment is both effective and safe for MDD patients.

How Can Non-Invasive Brain Stimulation Be Used Beyond Depression?

Non-invasive brain stimulation (NIBS) has expanded its use beyond depression. These techniques can modulate brain activity, making them valuable for treating various neurological and psychiatric conditions.

• Anxiety Disorders: rTMS has been explored for anxiety disorders like generalized anxiety and panic disorders. It works by targeting brain regions involved in regulating anxiety and emotional responses, providing relief to patients who may not respond to traditional treatments.
• Chronic Pain: NIBS is also used to manage chronic pain, including conditions such as fibromyalgia and neuropathic pain. Stimulating certain brain regions helps reduce pain perception and improves the quality of life for those with long-term pain conditions.
• Stroke Rehabilitation: Brain stimulation is increasingly being applied to aid in stroke recovery. rTMS and tDCS can enhance motor function by stimulating areas of the brain that control movement. This therapy helps improve motor recovery and rehabilitation after a stroke.
• Cognitive Decline: NIBS techniques are being studied for their potential to treat cognitive decline in conditions like mild cognitive impairment (MCI) and Alzheimer’s disease. By promoting brain plasticity, these therapies can slow down the progression of cognitive impairments and improve memory and attention.

The non-invasive nature of these treatments makes them a safer option compared to more invasive procedures. As research continues, these techniques offer great promise for treating a wide range of conditions, providing new hope for patients who seek alternatives to traditional therapies.

How Is the TMS Institute of Arizona Leading the Way in Brain Stimulation Therapies?

TMS Institute of Arizona is dedicated to staying at the forefront of non-invasive brain stimulation therapies like rTMS and tDCS. With a team of leading experts in the field, we offer effective treatments to help patients overcome cognitive dysfunction, depression, and other mood disorders.

Our clinic specializes in:

• Advanced TMS therapy tailored to individual needs
• Personalized treatment plans combining innovative approaches
• Evidence-based practices that have been shown to improve cognitive and emotional well-being

We know depression and cognitive dysfunction can feel overwhelming, but you’re not alone in this journey. Reach out to the TMS Institute of Arizona today. We make sure that you can live a healthier, happier life.

References

Li, X., Liu, J., Wei, S., Yu, C., Wang, D., Li, Y., Li, J., Zhuang, W., Luo, R.-C.-X., Li, Y., Liu, Z., Su, Y., Liu, J., Xu, Y., Fan, J., Zhu, G., Xu, W., Tang, Y., Yan, H., & Cho, R. Y. (2024). Cognitive enhancing effect of rTMS combined with tDCS in patients with major depressive disorder: a double-blind, randomized, sham-controlled study. BMC Medicine, 22(1). https://doi.org/10.1186/s12916-024-03443-7

‌ Gonda, X., Pompili, M., Serafini, G., Carvalho, A. F., Zoltán Rihmer, & Péter Döme. (2015). The role of cognitive dysfunction in the symptoms and remission from depression. Annals of General Psychiatry, 14(1). https://doi.org/10.1186/s12991-015-0068-9

Lam, R. W., Kennedy, S. H., McIntyre, R. S., & Khullar, A. (2014). Cognitive Dysfunction in Major Depressive Disorder: Effects on Psychosocial Functioning and Implications for Treatment. The Canadian Journal of Psychiatry, 59(12), 649–654. https://doi.org/10.1177/070674371405901206

‌Note: The information provided here is based on research findings. Always consult a doctor for individualized medical advice.