Epilepsy is one of the most common neurological disorders worldwide, affecting approximately 50 million people. Its impact extends beyond recurrent seizures, influencing employment, education, relationships, independence and quality of life. Stigma and discrimination can add to these challenges, while depression and anxiety are among the psychiatric conditions that occur more frequently in people living with epilepsy (WHO, 2024).
Depression is a particularly important concern. A systematic review and meta-analysis published in Neurology estimated that 23.1% of people with epilepsy experienced active depression, with the odds of depression approximately 2.8 times higher than in people without epilepsy (Fiest et al., 2013). More recent meta-analytic evidence estimated the pooled prevalence of depression at 27% in population-based studies and 34% in clinical settings (Qin et al., 2022). Although these estimates differ because of variations in populations and assessment methods, they highlight the substantial burden of depression in epilepsy.
The relationship between the two conditions may also be more complex than a straightforward cause-and-effect relationship. Research suggests that epilepsy is associated with an increased risk of subsequently developing depression, while depression is also associated with an increased risk of subsequently developing epilepsy (Bølling-Ladegaard et al., 2023).
This raises an important clinical question: if depression and epilepsy are closely connected, could effective treatment of depression contribute to better patient care and quality of life?
One potential approach is transcranial magnetic stimulation (TMS), which is a establish treatment used for depression. NICE guidance describes TMS as a treatment that can be delivered on an outpatient basis without anaesthesia, commonly over a course of repeated sessions (NICE, 2022).
However, TMS treatment in people with epilepsy presents a particular clinical consideration: TMS can, although uncommonly, induce seizures (Pereira et al., 2016). This creates an important balance between the potential benefit of treating depression and the need to maintain seizure safety.
This article explores the relationship between epilepsy and depression, why TMS may be relevant to this population, what the current evidence tells us about safety and clinical potential, and how TMS could contribute to a more integrated approach to patient care.
The association between epilepsy and depression is well established, but its underlying causes are complex. Living with epilepsy can involve more than managing seizures. Their unpredictability may create uncertainty about everyday activities, future plans and personal independence depending on individual circumstances. Stigma and fear of discrimination can further affect social participation and psychological wellbeing (WHO, 2024). These factors provide an understandable pathway through which epilepsy may contribute to depression.
However, psychological and social factors do not fully explain the relationship between epilepsy and depression. Research suggests that the two conditions may share underlying neurobiological mechanisms, including alterations in neurotransmitter systems and dysfunction in overlapping brain networks involved in emotional regulation and neuronal excitability. These potential shared mechanisms may help explain why epilepsy and depression are associated bidirectionally, rather than one condition being solely a consequence of the other (Kanner, 2011; Jones and Maguire, 2024).
The bidirectional relationship is supported by large-scale epidemiological research. A nationwide register-based cohort study involving approximately 8.7 million people found that epilepsy was associated with an increased rate of subsequently developing depression, with an adjusted hazard ratio of 1.88. Conversely, depression was associated with an increased rate of subsequently developing epilepsy, with an adjusted hazard ratio of 2.35 (Bølling-Ladegaard et al., 2023).
These findings are important, but they require careful interpretation. Hazard ratios describe relative rates over time rather than an individual's absolute probability of developing a condition. Furthermore, an association does not establish that depression directly causes epilepsy or vice-versa.Instead, the findings suggest that the conditions may influence one another or share common biological, psychological and social vulnerabilities.
The clinical implications are significant. Depression should not be considered solely a consequence of poorly controlled seizures, nor should its assessment be restricted to particular stages of epilepsy. Routine recognition of depressive symptoms can help identify people who may benefit from psychological support, medication or specialist mental health treatment.
Antiseizure medications and other aspects of epilepsy management may also influence mood in some individuals. Consequently, assessing depression requires consideration of the person's wider clinical circumstances, rather than assuming that symptoms have a single cause.
Depression in people with epilepsy should not be viewed as a condition for which conventional treatments are automatically unsuitable. Evidence-based psychological and pharmacological treatments remain important components of care.
The International League Against Epilepsy (ILAE) has published clinical practice recommendations for treating depression in adults with epilepsy. These recommendations support psychological interventions for mild depressive episodes and identify selective serotonin reuptake inhibitors (SSRIs) as first-choice antidepressant medications when pharmacological treatment is appropriate, including for moderate-to-severe depression (Mula et al., 2022).
However, not everyone experiences sufficient improvement with these approaches. Some people continue to experience significant symptoms despite appropriate treatment, while others may have difficulty tolerating medication or may prefer to consider additional options after discussing the benefits and risks with their clinicians.
This is where TMS may have a potential role - unlike antidepressant medication, TMS does not rely on systemic pharmacological exposure. Instead, it uses magnetic pulses to influence activity in targeted cortical regions and the distributed neural networks involved in mood regulation.
For depression, commonly used TMS protocols target the dorsolateral prefrontal cortex (DLPFC). Treatment approaches include high-frequency stimulation of the left DLPFC and low-frequency stimulation of the right DLPFC. Intermittent theta-burst stimulation is another approach used in depression treatment.
The broader evidence base for TMS in depression is substantial. An international consensus review published in Clinical Neurophysiology in 2025 concluded that TMS continues to demonstrate broad evidence for safety and efficacy in treating depression, while also highlighting the continuing development of newer and accelerated protocols (Trapp et al., 2025).
But what happens when the person receiving TMS also has epilepsy?
The potential use of TMS in patients with epilepsy presents a particular clinical challenge – TMS deliberately influences cortical activity, whereas epilepsy involves an increased susceptibility to abnormal electrical activity that can result in seizures. The obvious concern is therefore whether stimulation could trigger a seizure.
The available evidence suggests that seizure induction is possible but uncommon. A systematic review examining the safety of TMS in people with epilepsy identified 426 participants across 40 studies. Among 410 participants included in the seizure-risk analysis, 12 experienced seizures, giving a crude per-person seizure risk of approximately 2.9%. The authors concluded that the risk of seizure induction was small but highlighted important limitations in the evidence, including differences between studies and the potential influence of participants' baseline seizure activity (Pereira et al 2016).
However, it is important to note that this figure should not be interpreted as a universal risk for every person with epilepsy receiving TMS. The studies included different epilepsy populations, clinical circumstances and stimulation protocols. Some were also investigating TMS in the context of epilepsy itself rather than treating depression. Individual risk may depend on factors including seizure control, epilepsy type, stimulation parameters, current medication and other factors that may influence seizure threshold.
Consequently, the clinical question is not simply whether TMS is “safe” or “unsafe” in epilepsy. Instead, it is whether TMS can be delivered safely to carefully selected patients using appropriately considered treatment protocols.
One of the challenges in this area is that much of the evidence surrounding TMS comes from either depression in people without epilepsy or people with epilepsy in which TMS was being investigated for seizure control. There has historically been much less research specifically examining TMS for depression in people with epilepsy.
The evidence supporting TMS as a treatment for depression in the general population is substantially more established than the evidence specifically relating to people with epilepsy.
A 2025 international consensus review by Trapp et al. found that TMS has a broad evidence base supporting its safety and efficacy in depression. The review also emphasised the importance of appropriate clinical assessment, treatment delivery and consideration of special populations. However, these findings cannot simply be extrapolated to people with epilepsy, who may have a different underlying susceptibility to seizures.
Recent research specifically focused on epilepsy is starting to emerge. A 2026 study investigated accelerated low-frequency TMS for treatment-resistant depression in people with epilepsy. Twelve adults received accelerated 1-Hz TMS targeting the right dorsolateral prefrontal cortex. The intervention was well tolerated, and no increase in seizure frequency was observed at one or six-month follow-up. The study also reported significant improvements in depressive symptoms (Bujarski, et al 2026).
These findings are potentially important because they provide direct clinical evidence that TMS can be investigated in people who have both epilepsy and treatment-resistant depression. They also raise the possibility that carefully selected stimulation protocols may allow clinicians to address depressive symptoms without adversely affecting seizure control.
However, the limitations of the study are equally important. The study was a small, open-label study without a sham-control group. Because of that, the results cannot establish with certainty that TMS itself was responsible for the improvement in depression, and the study was too small to provide reliable estimates of uncommon adverse events. The results should therefore be regarded as preliminary evidence of feasibility and potential, rather than definitive evidence of efficacy.
Larger randomised controlled trials will be needed before clear conclusions can be made about how effective and safe TMS is specifically for people with epilepsy.
The relationship between TMS and seizure risk cannot be considered independently of how stimulation is delivered. TMS is not a single standardised treatment - different protocols vary in stimulation frequency, intensity, duration, number of pulses and treatment schedule. These parameters influence the physiological effects of stimulation and are therefore relevant when considering seizure risk.
The contemporary TMS safety literature recognises seizure as a rare but important adverse event and emphasises the importance of considering both treatment-related and individual risk factors (Trapp et al., 2025).
The ILAE makes a particularly relevant point in its recommendations for depression in epilepsy: TMS may be an option for patients whose depression has not responded sufficiently to pharmacotherapy, but the parameters used to treat depression may differ from those safely used when TMS is being used to treat epilepsy (Mula et al., 2022).
This reinforces the importance of individualised clinical assessment. Before treatment, clinicians may need to consider factors including seizure frequency and recent seizure control; epilepsy type and underlying neurological diagnosis; previous response and tolerability of depression treatments; the proposed TMS protocol and stimulation parameters, for example.
For people living with epilepsy, the potential value of treating depression lies in what meaningful improvement could mean in everyday life. Effective treatment may help address depressive symptoms which could potentially support engagement with treatment, relationships, social participation, employment or education and overall quality of life. These outcomes are particularly relevant in epilepsy, where the impact of the condition frequently extends beyond seizure frequency alone.
The current evidence provides reason for interest, but not yet definitive answers. TMS is an established treatment for major depressive disorder, supported by a substantial evidence base in the general population. In people with epilepsy, however, evidence specifically addressing the treatment of depression remains comparatively limited.
The available research suggests that seizures associated with TMS are uncommon, while emerging epilepsy-specific research indicates that carefully selected low-frequency protocols may be feasible for people with treatment-resistant depression. The 2026 Bujarski study represents a valuable step in this direction, but its findings need to be confirmed by larger and more detailed studies.
The next stage is therefore not simply to ask whether TMS can be used in epilepsy, but to determine how it can be used most safely and effectively, and for whom. People with epilepsy differ in seizure type, underlying cause, seizure frequency, medication, psychiatric history and other clinical characteristics. Understanding how these differences influence treatment response and safety will be important if TMS is to become more widely incorporated into epilepsy care.
Larger controlled studies could also help clarify optimal stimulation parameters, identify patient characteristics associated with greater benefit or risk, and establish whether improvements in depression translate into meaningful changes in quality of life and broader clinical outcomes.
For clinicians, this evidence may ultimately support a more personalised approach to treating depression in epilepsy. For patients, it could mean having access to a wider range of treatment options when conventional approaches have not provided sufficient benefit. Ultimately, the value of TMS should be assessed in terms of both clinical outcomes and its contribution to the person's overall wellbeing.
Depression is an important and sometimes under-recognised aspect of epilepsy, with implications for quality of life, social participation and overall wellbeing. The bidirectional association between the two conditions reinforces the importance of recognising and treating depression as part of comprehensive epilepsy care.
Transcranial magnetic stimulation offers a potential additional treatment option for people whose depression has not responded adequately to established treatment. Its efficacy in major depressive disorder is supported by a substantial evidence base, but the evidence specifically addressing depression in people with epilepsy remains limited. Nevertheless, recent studies looking at accelerated low-frequency TMS provides encouraging preliminary evidence of feasibility and potential clinical benefit in people with treatment-resistant depression and epilepsy.
The next step is to establish which patients are most likely to benefit, which stimulation protocols are most appropriate, and how treatment affects both depressive symptoms and seizure outcomes over time. Larger controlled studies incorporating quality of life, cognitive functioning, treatment tolerability and longer-term follow-up will be essential. For patients, that could ultimately mean care that looks beyond seizure control alone and considers the person as a whole.
Written by Rogelio, Smart TMS Manchester Practitioner
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