TMS for depression

Transcranial Magnetic Stimulation (TMS) has been used against depression for several decades, yet there remains deep scepticism among both patients and doctors over whether it really works.

Applying magnets to the brain might seem like a cross between a voodoo ritual and experiments in electricity in Victorian England. Either way it can look a lot like pseudoscience, especially since a recipient merely needs to sit there – no anaesthetic, no recovery time, no pain – and somehow the magnets do their work. Replace magnets with healing crystals and the picture would be complete.

When discussing TMS with psychiatrists unfamiliar with the technique, objections arise thick and fast. The most common viewpoint among the sceptical is that TMS is “unproven”, or “no better” than older methods.

When offered studies that show that TMS is superior – for example, for treatment-resistant depression – the reply quickly comes back that they “need more evidence” and “we’ll wait and see”. The prevailing opinion seems to be that only overwhelming experimental data will change their approach. Such a mindset is nothing new, and not necessarily bad.

Psychiatrists tend to be intensely sceptical of any new treatment, especially anything that departs from the usual mould of medication and psychotherapy. To be gung-ho about a treatment that ultimately reveals itself as useless is to be a dupe, a sucker, a bad psychiatrist. With too many empty promises filling TV and social media, to fall in with the hype is to jettison what sets a psychiatrist apart: training, experience, and clinical wisdom.

There have been too many failures to risk credulity, and too much to lose by being wrong. Far better to remain aloof and sceptical. At worst, the careful psychiatrist will be a little behind, and that is certainly superior to being naïve.

Meanwhile the public knows little about TMS at all. A quick straw poll of online opinions showed that while most have heard of TMS, few knew what it was for.

Those who could name depression assumed TMS was a treatment of last resort. Some thought of it as a new form of ECT and simply transferred their negative impressions. With patients unaware and doctors sceptical, adoption of TMS lags well behind its potential benefit.

To help address this gap, NeuroCentrix recently ran a study of TMS in depression, but with a twist. Almost all existing TMS studies have looked at a very select group of patients in a very specific setting, namely depression where other treatments have failed.

While these studies provide important evidence that TMS does work, they also reinforce the assumption that TMS is mostly for research or intractable cases. Patients with other conditions or using other treatments are excluded as much as possible from these trials, but in reality, most people who need treatment will have these features and many more.

Previous trials have also been restricted to the specific TMS protocol under investigation, with the same intensity, frequency, site and number of sessions. In practice these vary enormously. In the real world neither the patients nor the treatments fit the box that research decrees.

And so this study took all patients who had received TMS for whatever reason, and then assessed the effect retrospectively. Patients were neither handpicked nor excluded. The result was a large sample that represented real-life patients receiving TMS in a real-world setting.

The patients were assessed with rating scales at admission and discharge, and these numbers were analysed and compared. The total number of participants was 229, with 135 women and 94 men. They were of all ages, ranging from 19 to 89. Of the total number, 104 of the participants had more than one admission, and these further admissions were also included.

A review of the patient files indicated that each participant had been experiencing moderate to severe depressive symptoms, and major depressive disorder was the most common primary diagnosis. Yet depression alone is not the only way to be depressed, and many patients suffer depressive symptoms from another disorder. And so in this study featured a variety of conditions encompassing the whole range of psychiatric pathology, including alcohol abuse, ADHD, OCD, bipolar disorder, schizophrenia and personality disorders.

The only patients not included in the sample were those which could not be compared because of missing data, such as an incomplete discharge assessment.

Once all the statistical analyses were complete, the results of the study were clearly positive. Across all measures, symptoms of depression had decreased after TMS treatment. Not only did the results easily pass the test for statistical significance, but the improvement was substantial.

On average, a patient’s change in score was sufficient to move down one or two severity ranges, such as from severe to moderate or mild. Statistical analysis also revealed that the initial treatment produced a larger effect than subsequent treatments, which fits the expected law of diminishing returns.

Another important outcome of the study was that patients who recorded a mild severity of depression also benefited. Since most studies have involved patients with severe or treatment-resistant depression, this finding fills in a crucial gap in existing research.

Overall, the conclusion was unequivocal: an admission for TMS treatment has a significant antidepressant effect.

A potential criticism of the study is that patients may have improved from whatever treatment they had during their stay, not necessarily the TMS. Here is one drawback of the “real-world” approach.

By not excluding patients that receive other treatments, the benefit of these treatments would be lumped in with the TMS. However, this criticism is not as strong as it appears since any other treatment would usually already be in place before admission, and any treatment changes would be coincidental and insignificant compared to the reason for the admission, the TMS itself.

Changes to medication or psychotherapy, for example, do not require admission and could occur at any time, thus having no effect on the period under study. In fact, such changes would be more likely to occur apart from, rather than during, an admission for TMS.

Psychiatrists generally change only one treatment at a time, or there would be no way of knowing which change was responsible for the outcome. Such caution would be even more tightly applied when undertaking a novel and time-consuming treatment like TMS, since the understanding its impact would be crucial in deciding future management.

Meanwhile in the hypothetical cases where medications were changed during admission, any resulting benefit would likely not appear until well after discharge. A new antidepressant, for example, takes 4 to 6 weeks to reach its effect, which would accordingly not influence the assessment taken at discharge.

Another concern would be that patients might not leave until improved, and thus depression scores would naturally be better at discharge than admission. Ideally patients would improve during their stay, but this is not how admissions occur in practice.

Length of stay is usually capped regardless of outcome, and admissions for TMS are generally planned for a set period. The depression score at discharge therefore escapes this potential bias.

In fact, since discharge is often shortly after treatment, the discharge assessment may underestimate the benefit by assuming that any effect happens immediately.

Neuroscientific studies on the effects of TMS suggest a complex pathway that involves several much slower mechanisms, such as synaptic growth and restored neuronal connectivity. Together these processes fall under the term “neuroplasticity”, a phenomenon that takes weeks or even months to develop, and would certainly remain invisible to an assessment taken at discharge.

While the study cannot remain impervious to all criticisms, the size of the effect strongly suggests that overall the positive result is sound. The study indicates that TMS is effective for depressive symptoms over a large sample size which includes a variety of comorbidities, diagnoses, medications, lengths of stay, treating clinicians, protocols employed, and treatments delivered.

We can comfortably conclude that TMS is a viable and effective option for depressed patients in the real world.

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The information has been taken from Effectiveness of TMS for depression in a real-world setting. Andy Utley, Luke Ainsworth, David Barton, Peter Farnbach, Shane Costello, & Jake Kraska (publication to follow).

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