In older individuals, treatment-resistant depression (TRD) is frequent. TRD has been successfully treated with 48 minutes of bilateral repeated transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex. Theta burst stimulation (TBS), a more recent variation of rTMS, may also be applied bilaterally for only 4 minutes utilizing left intermittent and right continuous TBS. For a study, researchers sought to determine if TBS was more effective and tolerable in older persons with TRD than traditional rTMS.

Recruitment occurred in the blinded assessor, open treatment, randomized noninferiority study between December 2016 and March 2020. The study was carried out at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada. Outpatients 60 years of age and older with a diagnosis of moderate severity depression and nonresponse to 1 or more antidepressant trials of adequate dosage and duration or intolerance of 2 or more trials were included. Bilateral standard rTMS or TBS was given to participants randomly for 4 to 6 weeks.

The change in the Montgomery-Åsberg Depression Rating Scale served as the primary outcome indicator. Secondary outcome indicators were dropout rates, the 17-item Hamilton Rating Scale for Depression, and the Quick Inventory of Depressive Symptomatology (16-item). The primary outcome was determined using a noninferiority margin of 2.75 points. All individuals who reached the 4-week main completion point underwent analysis. 

A total of 85 participants (mean [SD] age: 66.3 [5.3] years; 45 [52.9%] female) were randomized to TBS, and 87 participants (mean [SD] age: 67.1 [6.7] years; 47 [54.0%] female) were randomized to standard bilateral rTMS. Of these, 85 (98%) and 79 (93%) participants received assessments for the primary outcome, whereas tolerability was evaluated in all were randomized participants. In the rTMS group, 5 (5.8%) were Asian, and 4 (4.6%) were American Indian, reported other, or decided not to respond, and 78 (89.7%) were White. In the TBS group, there were 6 (7.1%) Asians, 2 (2.4%) Blacks or reported other races and 77 (90.3%) Whites. The mean (SD) Montgomery-Åsberg Depression Rating Scale total scores for rTMS increased from 25.6 (4.0) to 17.3 (8.9) and for TBS from 25.7 (4.7) to 15.8 (9.1) for TBS (adjusted difference, 1.55; lower 95% CI -0.67), proving TBS’ noninferiority. The percentages of dropouts for all reasons were comparable between the groups (rTMS: 2 of 87 [2.3%]; TBS: 6 of 85 [7.1%]; P =.14; X2 = 2.2).

Bilateral TBS compared to regular bilateral rTMS produced a non-inferior decrease in depressive symptoms in older people with TRD. Dropout rates were low and comparable for both regimens. For older persons with TRD, using TBS rather than rTMS might greatly enhance access to therapy.

Reference: jamanetwork.com/journals/jamapsychiatry/fullarticle/2796747