Transcranial magnetic stimulation and the treatment of suicidality

Keywords::

• brain stimulation
• depression
• suicide
• transcranial magnetic stimulation

Suicidal behavior is a complex medical and social problem [1,2]. More than 90% of suicides are associated with mental illnesses, and 60% of them occur in the context of depressive disorder, although almost all psychiatric disorders are characterized by an increased risk of suicidal behavior. Therefore, the existence of suicidal syndromes independent of psychiatric illnesses has been proposed [1,2]. Suicidal behavior may be understood as a function of the interplay between state-dependent factors, such as illness and life events, and trait-dependent factors, which include biological markers for suicidal behavior. Suicidality can occur in association with different mental states and psychiatric conditions. Suicide attempts are often very difficult to predict [2]. Despite advances in research and treatment of psychiatric disorders and suicidal behavior, in recent years suicide rates have not been decreasing [101].

There are very few treatments for suicidality (e.g., lithium, clozapine and dialectical behavior therapy). These treatments are only partially effective. It is clear that current treatments for suicidality are inadequate and there is a great need to develop new treatment modalities. Ideally, a treatment should improve mood state and modulate certain personality traits, such as aggression, impulsivity and pessimism. Transcranial magnetic stimulation (TMS) has been shown to influence affective and cognitive states [3–5], in both shorter and longer time frames [3–5], and may be considered as a potential treatment to reduce sucidality.

Transcranial magnetic stimulation consists of rapidly alternating magnetic fields applied to the scalp to induce small, focal electrical currents in the superficial cortex [3–5]. TMS involves low (single-pulse and <1 Hz TMS) to high (>1 Hz to ∼50 Hz) frequency, single-pulse to repetitive TMS (rTMS), for research and clinical applications. Single-pulse TMS is used primarily in diverse neuroscience research paradigms, often with functional MRI, PET and electroencephalography (EEG), to investigate basic cognitive and neural functions. TMS is the appropriate term for low-frequency stimulation, or is often used as the generic name; rTMS is the appropriate term for stimulation greater than 1 Hz, involving brief bursts of repeated magnetic stimulation. TMS is a magnetic, nonconvulsive, low-invasive intervention that does not require sedation. It has moderately high focality and high power, and is externally administered. Many studies have concluded that, when used according to safety guidelines, TMS is safe, and causes no known side effects beyond occasional headache, and very rarely, seizure or tinnitus [6,7].

There are no studies to date of TMS specifically used to reduce suicidal ideation or behavior. What is the evidence that TMS might be able to modulate either conditions associated with suicidality, and/or the immediate affective and cognitive precursors of sucidality, in such a way as to prevent the preconditions or desire for suicide?

The first type of relevant and encouraging evidence is that for many of the major mental health conditions most frequently associated with suicidal behavior – major depression, bipolar disorder and schizophrenia – rTMS is showing some efficacy, using different brain site targets and stimulation parameters, as indicated by theory and research precedent [3–5,8,9]. TMS is being investigated for depression [8,9], anxiety [10], obsessive compulsive disorder [11,12], sleep disorders [13], substance abuse [14,15] and post-traumatic stress disorder [16,17], all conditions associated with suicide. Evidence is encouraging for treatment of the positive, often suicide-associated, symptoms of schizophrenia (e.g., auditory command hallucinations), as well as the negative ones [18,19].

There are no published reports that TMS causes suicidality [20]. In recent years, concern has increased that the selective serotonin reuptake inhibitors often prescribed for depression might increase suicidality, particularly in adolescents and young adults [21]. Currently, there is insufficient evidence that TMS would never provoke suicidality in youth. However, several studies on the possible benefits of TMS for epilepsy, depression and other conditions have been conducted on young people [22–24]. It is possible that younger, less treatment-resistant patients might benefit the most from TMS. A pooled analysis of close to 200 depressed patients demonstrated that age and treatment refractoriness were significant negative predictors of depression improvement with TMS, and TMS antidepressant therapy in younger and less treatment-resistant patients was associated with better outcome [25]. TMS is also being used experimentally to enhance brain plasticity and recovery of function [26]. However, the possibility does exist that the use of TMS in young people whose brains are still developing might pose risks of interfering with normal development.

These many results show that TMS can modulate mood and related states. This alone suggests its potential usefulness in mitigating the preconditions for suicide, not least because improved mood also yields improved memory, attention and executive functions, and as a consequence generally promotes more balanced and rational thought processes.

The second type of evidence for the possible usefulness of TMS for suicidality is less clinically derived, and more rooted in the many paradigms being developed for cognitive neuroscience investigations of many brain areas and functions [27]. Multiple phenomena are being investigated [3–5,28–30]. We will cite only a few examples that may have eventual relevance, directly or by analogy, to modifying the preconditions for suicidality. Recent studies reveal that TMS can influence types of inherent personal and interpersonal cost–benefit calculations, for example, choosing immediate rewards over larger delayed rewards [31]; or the neural underpinnings of self-control and temptation in the context of preserving personal reputation [32]. An EEG study demonstrated that a specific neural marker – baseline cortical activity in the right prefrontal cortex – predicted individuals’ desire to mete out punishment to norm violaters (in an experimental scenario) [33]. It may be possible, for example, to use TMS to try to modulate this silent indicator of future behavioral choice. If a similar cortical marker for emotional and decision processes highly relevant to aspects of suicidality were to be identified, in theory, TMS could be used to modulate them. Knoch et al. wrote that, “analysis of task-independent individual variation in cortical baseline activity provides a new window into the neurobiology of decision-making by bringing dispositional neural markers to the forefront of the analysis” [33]. This type of paradigm and analysis is needed in suicidality research.

In general, cognitive and perceptual impacts of TMS in the above types of research paradigms are short lived, rarely lasting much longer than the time frame of the experimental episode. Furthermore, the above results have been obtained almost exclusively in normal volunteers. Using TMS, if one were seeking to create cognitive re-adjustment of moral, emotional, economic and other decision biases and similar phenomena in individuals at risk for suicide, it is difficult to see how TMS could be applied therapeutically, both at a critical moment and with enduring impact, given that acute suicidal behavior is often difficult to predict. However, new developments in mostly nonclinical TMS research, and also the possibility of initiating study of TMS effects on subtle, behaviorally silent processes within clinical trials whose primary focus is treating psychiatric illnesses, might sooner tell us if, for example, 6 weeks of daily rTMS has an impact on emotional, social and cognitive decision-making relevant to suicidality. There are considerable impediments – logistical, scientific and ethical – to trying to add neuroscience research tasks to clinical trials, but these may be soluble.

More relevant in the immediate future is the use of TMS to normalize mood and restore healthier brain function as much as possible, to prevent states of mind most associated with despair, or disinhibition of irrational, aggressive and impulsive tendencies. Daily interpersonal contact of approximately 1–2 h over 6–8 weeks with the treating psychiatrist and other brain stimulation personnel may also provide more structure and comfort, and may afford more opportunities to interact and monitor patient status, possibly increasing the likelihood of catching warning signs of possible suicide attempts.

Transcranial magnetic stimulation continues to evolve technically on several fronts. In the near future, deep brain TMS and other advances will make it more possible to penetrate the brain more deeply with still relatively low-invasive magnetic stimulation, and with increasing control over stimulation parameters [34,35]. These developments have great relevance for the future of TMS to treat suicidality and its associated mental health conditions, as many key brain areas that may be implicated may require deeper brain stimulation than rTMS can deliver.

In conclusion, TMS is not a treatment of suicidality, although for many reasons that we sought to review above, there is reason to think it might become one. We suggest there is a great need for more diverse research into this possibility.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.