Depressive Episodes Among Patients With Bipolar Disorder Not Effected by Intermittent Theta Burst Stimulation Therapy

depressed woman
depressed woman
This study looked at whether intermittent theta burst stimulation (iTBS) transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex is safe and efficacious in acute bipolar depression.

Intermittent theta burst stimulation (iTBS) of the left dorsolateral prefrontal cortex (LDPFC) was not effective treatment for major depressive episodes among patients with bipolar disorder. These findings, from a randomized, double-blind clinical trial, were published in JAMA Network Open.

Patients (N=37) with bipolar disorder were recruited from the University of British Columbia and the University of Calgary in Canada between 2016 and 2020. Participants were randomized to 4 weeks of active iTBS (n=18) or sham (n=19) treatment which comprised 600 pulses of 50 Hz triplets repeated at 5 Hz (2 seconds on, 8 seconds off) targeted at the LDPFC. Depression was assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline, 2, and 4 weeks.

Patients were aged mean 43.86 (standard deviation [SD], 13.87) years, 62.2% were women, 91.9% were White, 56.8% had bipolar disorder type 1, 48.6% were on a mood stabilizer and atypical antipsychotic, and the current depressive episode has lasted an average of 32.45 (SD, 34.29) weeks.

The decrease in MADRS depression score among patients who believed they had active iTBS was 47.47% (SD, 30.44%) and among those who believed they received sham treatment was 14.84% (SD, 22.03%; t[28], 3.41; P =.002). The distribution of patients believing they were receiving sham or active treatment was center specific (P =.03).

Compared with baseline, patients reported a least-squares mean difference in MADRS of -1.36 (95% CI, -8.92 to 6.19; P =.91) favoring the sham treatment. A total of 3 patients in each group reported a clinical response of ³50%.

Stratified by bipolar types there was no effect of iTBS treatment (t[29], 0.33; P =.74). Stratified by medication, no effect was observed among patients who were on lamotrigine (t[13], 0.47; P =.64), lithium (t[13], 0.69; P =.49), or valproate (t[13], 0.54; P =.59).

This study may have been biased by the integrity of the site-specific blinding.

These data indicated there was little benefit from iTBS of the LDPFC for the treatment of depressive episodes among patients with bipolar disorder.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


McGirr A, Vila-Rodriguez F, Cole J, et al. Efficacy of active vs sham intermittent theta burst transcranial magnetic stimulation for patients with bipolar depression: a randomized clinical trial. JAMA Netw Open. Published online March 12, 2021. doi:10.1001/jamanetworkopen.2021.0963.