A new study tested transcranial magnetic stimulation (TMS) for treating people with a bipolar disorder diagnosis. The researchers found that actual TMS was no better than a sham (fake) treatment.
The study was led by Lakshmi N. Yatham at the University of British Columbia Hospital in Canada and published in JAMA Network Open.
The specific type of intervention used is intermittent theta-burst stimulation (iTBS), a type of TMS. The researchers targeted the left dorsolateral prefrontal cortex (LDPC) in the brain. The goal was to relieve depression symptoms in people diagnosed with bipolar disorder.
iTBS was used, and the LDPC was targeted because these are currently popular TMS methods in depression treatment. Yatham writes:
“There was no evidence of antidepressant superiority for active iTBS over sham iTBS, and safety is uncertain because 1 hypomanic switch occurred with active iTBS and a second occurred during the open-label phase.”
That is, people randomly assigned to the fake treatment did just as well as people who received actual iTBS. Additionally, two people undergoing actual iTBS became hypomanic—compared with none who were receiving the sham treatment.
The study was double-blinded, meaning that neither the participants nor the researchers knew who was receiving iTBS and who was receiving the sham treatment. The randomized, controlled trial lasted for four weeks, with an additional four-week “open-label” phase during which there was no sham control group.
The 37 participants were required to have a diagnosis of bipolar disorder I or II, be currently experiencing a major depressive episode, and be currently taking a mood stabilizer and/or an antipsychotic drug. They were also required to have had no “clinical response” to the drug—that is, for the participants in this study, mood stabilizers and antipsychotics did not work to improve their symptoms.
People who had previously had no response to TMS were excluded, as were people who were suicidal, experiencing psychosis or substance abuse, or undergoing psychotherapy.
The study was intended to include 50 people in each group (totaling 100). However, the study was canceled early because TMS was so inadequate. Response rates were very low: 3 of the 19 people in the sham treatment group improved, while 3 of the 18 people in the active treatment group improved.
After eight participants dropped out, 29 participants completed the four-week randomized trial. 21 people then agreed to enter the open-label phase. Five of them dropped out, leaving 16 people to complete the open-label trial. Four of the 16 remaining people “achieved clinical remission” during the open-label phase—but there was no control group to compare these results to, so they could also have been due to the placebo effect or regression to the mean.
Although the researchers write that “blinding integrity was preserved,” they note that about half of the people in the study correctly guessed whether they received the active treatment or not. Additionally, people were far more likely to improve if they believed they had received the active treatment—which is evidence of a strong placebo effect.
Surprisingly, TMS is approved by the FDA for the treatment of depression for people with any diagnosis, including bipolar disorder. The researchers note that this is based on extrapolating findings from studies on people with a depression diagnosis rather than any actual evidence on bipolar disorder.
Nonetheless, this isn’t the first study to demonstrate the ineffectiveness of TMS. A 2016 sham-controlled study of a different type of TMS (sequential bilateral repetitive transcranial magnetic stimulation) similarly found that the active treatment was ineffective in those with a bipolar disorder diagnosis.
Even in the treatment of people with a depression diagnosis rather than bipolar disorder, the evidence for the effectiveness of TMS is unclear. Three large, multisite trials found that TMS was ineffective.
A review by the Clinical TMS Society frames these findings positively, but the results are clear:
- The 2007 Neuronetics trial: Improvement after four weeks was not significantly different between active and sham TMS groups (p = 0.06). A p-value of less than 0.05 is usually considered statistically significant (sometimes, a p of less than 0.01 is used for an even stricter definition). The conclusion that this was “safe and effective” was regarded as having “the potential to mislead readers” by other researchers.
- In the 2010 OPT-TMS NIMH trial, 15% of people in the active TMS group improved (versus 4% in the placebo group). Although this difference was statistically significant, 85% of the participants did not improve after receiving TMS.
- The 2015 Brainsway trial: Although initial results were promising, remission rates for “Deep TMS” at the final outcome point of 16 weeks were not significantly different between active and sham groups (p = 0.15).
McGirr, A., Vila-Rodriguez, F., Cole, J., Torres, I. J., Arumugham, S. S., Keramatian, K., . . . & Yatham, L. N. (2021). Efficacy of active vs. sham intermittent theta-burst transcranial magnetic stimulation for patients with bipolar depression: A randomized clinical trial. JAMA Netw Open, 4(3), e210963. doi:10.1001/jamanetworkopen.2021.0963 (Link)