Antidepressant brain stimulation: Promising signs or continuing doubts?

Post written for the BPS Research Digest by guest host Chris Chambers, senior research fellow in cognitive neuroscience at the School of Psychology, Cardiff University, and contributor to the Guardian psychology blog, Headquarters.

Depression is a growing public health concern, affecting 1 in 9 people at some point in their lives, and with a third of sufferers experiencing little or no benefit from medication. The World Health Organization predicts that by 2020 depression will become the second leading cause of disability worldwide. By 2026 it is expected to afflict nearly 1.5 million people in the UK, costing the economy more than £12bn every year.

Faced with this crisis, scientists have looked for alternative solutions to medication. Since the mid 1990s there has been a steady interest in developing brain stimulation methods as antidepressants, particularly for patients who are resistant to drug therapy. The general logic of this approach is that because depression is associated with abnormally low activity in the left prefrontal cortex, methods that increase prefrontal activity, such as transcranial magnetic stimulation (TMS), might help promote recovery.

A new Taiwanese study now reports that a particularly potent form of transcranial magnetic stimulation called theta burst stimulation could lead to benefits in treatment-resistant depression. Cheng-Ta Li and colleagues compared the efficacy of three different types of theta burst stimulation: a protocol believed to increase activity in the left prefrontal cortex, one that reduces activity in the right prefrontal cortex, and a combined protocol that seeks to achieve both in the same treatment session. Compared with sham (placebo) stimulation, the team found that two weeks of daily treatment using the combined protocol was most effective, reducing self-ratings of depression by about 35 per cent.

These results are promising but preliminary. The sample size was small, including just 15 patients per group, and the trial was not preregistered. Such limitations are common in a literature that is dominated by controversy and small exploratory reports. A major 2007 study, which concluded that TMS is clinically effective (and which led to the treatment becoming approved by the FDA) was later criticised for selectively reporting positive outcomes, deviating from its registered analysis protocol, and being contaminated by uncontrolled placebo effects. The most recent review of evidence to date concluded that the benefits of TMS, while measurable statistically, are so small as to be clinically insignificant. And as to how these benefits of TMS arise in the first place – well, the truth is we have almost no idea. Our best guess is 'because dopamine'.

These uncertainties, in turn, raise concerns about ethics and regulation. With a growing number of companies offering TMS as a private healthcare intervention, and with standard treatments running into thousands of pounds, the fact that its efficacy remains unproven and unexplained is especially pertinent.

Notwithstanding these issues, this latest study by Li and colleagues is a helpful addition to the literature and suggests that more potent neurological interventions, such as theta burst stimulation, have potential. But realising that potential will require a commitment to rigorous and unbiased research practices. We need meticulously preregistered studies to prevent negative findings being censored and to ensure that authors don't cherry pick analyses that 'work' or engage in other questionable research practices. We need studies with larger samples to determine which individual differences determine the efficacy of TMS and to generate reproducible effects. And we need a renewed focus on understanding the neurobiology underlying any benefits of TMS.

Once these challenges are met, brain stimulation may well provide a complementary treatment for depression. For now, though, the jury is out.

_________________________________

Li CT, Chen MH, Juan CH, Huang HH, Chen LF, Hsieh JC, Tu PC, Bai YM, Tsai SJ, Lee YC, & Su TP (2014). Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. Brain : a journal of neurology PMID: 24817188