If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
], acute phase treatment was administered on a once-daily schedule of five sessions/week for the first four-six weeks. This schedule has been adopted in TMS clinical practices for the past decade.
Fig. 1a. Distribution of the longest period between any of two consecutive TMS sessions (MaxGap); b. Nonsignificant correlation between %Change IDS-SR and MaxGap; c. Nonsignificant correlation between %Change IDS-SR and TSD30.
Circumstances preventing strict adherence to this standard schedule (i.e. holidays, travel plans, illnesses/injuries) occasionally arise. A randomized clinical trial demonstrated that a TMS schedule of three sessions/week was not inferior to the standard five/week regimen on final treatment outcomes, though the group assigned to daily sessions achieved symptom reduction in a shorter period of time [
A randomized trial comparing repetitive transcranial magnetic stimulation given 3 days/week and 5 days/week for the treatment of major depression: is efficacy related to the duration of treatment or the number of treatments?.
]. In that study, however, participants who dropped out due to lack of efficacy were not included in the outcome analyses, and presumably all who were analyzed adhered to their assigned treatment schedule (3 or 5 per week).
A very practical question remains for depressed patients and their TMS clinicians: is missing scheduled sessions during the acute phase associated with inferior outcomes? If so, does it matter if lapses in consecutive treatments occur earlier or later in the course?
To address this question, we retrospectively reviewed deidentified data from 316 naturalistically-treated MDD patients undergoing an initial acute course of TMS therapy between 2010 and 2019 at Butler Hospital’s TMS clinic, initiated with the standard “on-label” 10 Hz protocol (3000 daily pulses at a 120% intensity relative to individual motor threshold) delivered to the left dorsolateral prefrontal cortex.
Treatment dates for all sessions (excluding final taper-phase, which includes intentional gap days), were ascertained using the NeuroStar software system. Maximum treatment gap (MaxGap) was calculated for each patient as the greatest number of successive days elapsed between any two consecutive sessions in their acute phase. Cases (n = 13) with MaxGap>14, a period comprising more than one-third of the standard acute phase, were excluded from the analyses.
For each participant, we examined treatment schedule density (TSD) ratio, calculated as (total number of TMS sessions)/(total number of days required to deliver those sessions), with a higher value corresponding to more consecutive treatment days. TSD was calculated for blocks representing the first 5 (TSD5), 10 (TSD10), 15 (TSD15), 20 (TSD20), and 30 (TSD30) sessions. A patient starting their course on a Monday and completing the first 5 sessions without a break would have TSD5 = 5 sessions/5 days = 1.0. Since the clinic is closed on weekends, a patient starting the first session on a Wednesday and not missing any scheduled visits would have TSD5 = 5 sessions/7 days = 0.71. Starting on a Monday without missing a scheduled treatment would have the highest possible density value for TSD30, 30 sessions/40 days = 0.75.
Inventory of Depressive Symptomatology Self Report (IDS-SR) and 9-item Patient Health Questionnaire (PHQ-9) total scores were used to calculate %change at endpoint (relative to pretreatment baseline); response on both measures was defined as ≥50% reduction in scores, with remission defined as a final total score of ≤13 on the IDS-SR and ≤4 on the PHQ-9. Analyses were conducted with endpoint scores obtained immediately after treatment 30 and also after the final treatment session (typically 36 or more, including 6 final treatments during a three-week taper phase). Last-observation-carried-forward (LOCF) values were used to calculate outcomes for patients terminating their course before session 30. T-tests compared responders versus nonresponders and remitters versus nonremitters. Pearson correlations examined associations between TSD blocks, MaxGap, and continuous outcome measures. All tests were 2-tailed with p = .05 for significance.
Of 303 patients (71% female, mean ± SD age 49.3 ± 15.1) included in the analysis, 63% had previous psychiatric hospitalizations and 26.7% had received at least one previous electroconvulsive therapy. Total number of delivered TMS sessions was 34.6 ± 6.8 (range, 6–52; median, 36). Mean baseline scores were 47 ± 10.2 on IDS-SR and 18.5 ± 5 on PHQ-9.
For the entire analysis sample, MaxGap ranged from 3 to 14(4.9 ± 2.1), but for most patients (90.1%) MaxGap was ≤7 (Fig. 1a). Among patients with MaxGap>7 (n = 30), main reasons for absence from TMS were nonpsychiatric medical conditions (n = 9), worsening psychiatric symptoms (n = 4), TMS treatment intolerability (n = 4), out-of-town travel/vacation (n = 3), holiday (n = 2), premature tapering off followed by clinical worsening and return to daily scheduling (n = 2), and other administrative or logistical reasons (n = 6). Eight patients had MaxGap>7 during their first 10 sessions, 11 between sessions 11–20, and 11 between sessions 21–30. MaxGap was not significantly correlated with PHQ-9 or IDS-SR %change at session 30 or with outcomes assessed after the final session (Fig. 1b). Mean MaxGap did not differ between responders/nonresponders or remitters/nonremitters.
A total of 244 patients completed ≥30 sessions; the majority who terminated their course before session30 did so due to lack of efficacy, however 15 patients who experienced early remission also finished their course with <30 sessions. Among 244 patients who received ≥30 sessions, the total number of days for 30 sessions ranged from 40 to 78 (48.5 ± 6.2), and the mean TSD30 was 0.63 ± 0.07. None of the TSD ratios significantly correlated with any of the outcome measures (e.g., Fig. 1c), suggesting that denser scheduling of treatments didn’t matter, whether it was in the first week, or in the first 2, 4 or 6 weeks. TSD mean values were not statistically different between responders/nonresponders and remitters/nonremitters. Findings were similar for outcomes immediately after session30 and the final session.
While we did not have a sufficiently formatted database to test whether patients with higher TSDs and lower MaxGaps were likely to experience improvement more rapidly than their counterparts, we found that modest nonadherence to the standard 5 sessions/week schedule had no meaningful impact on final depression outcomes. These results confirm that short lapses in the 5/week TMS treatment regimen, and even unanticipated gaps of up to 14 days during the acute phase, do not necessarily portend inferior prognosis.
The optimal treatment schedule for TMS therapy remains to be determined, and a pressing research question is whether more than one treatment per day will yield a more rapid yet durable antidepressant effect. At present, it can be assumed that equivalent outcomes can be expected for patients who have occasional absences during acute phase TMS therapy.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
A randomized trial comparing repetitive transcranial magnetic stimulation given 3 days/week and 5 days/week for the treatment of major depression: is efficacy related to the duration of treatment or the number of treatments?.
30219-9&id=gr1.jpg){kind=link}