Pubblicazioni

Repetitive Transcranial Magnetic Stimulation as Maintenance Treatment of Depression: The MAINT-R Randomized Clinical Trial

Noda, Y.; Wada, M.; Mimura, Y.; Taniguchi, K.; Tarumi, R.; Arai, N.; Tsugawa, S.; Thorpe, K. E; Daskalakis, Z. J; Uchida, H.; Mimura, M.; Blumberger, D. M; Nakajimair, S.; Moriyama, S.

Abstract:

Importance: depression relapse poses significant medical and economic challenges. Repetitive transcranial magnetic stimulation (rTMS) as maintenance treatment may prevent relapse of treatment-resistant depression (TRD). Objective: to compare the effectiveness between low-frequency rTMS and lithium in preventing TRD relapse. Design, setting, and participants: This randomized clinical trial was conducted from September 1, 2018, to May 31, 2023, at Keio University Hospital and Shinjuku-Yoyogi Mental Lab Clinic, Tokyo, Japan, among 75 participants with TRD aged 18 years or older with moderate-to-severe depressive symptoms despite at least 2 adequate antidepressant treatments who subsequently responded to an acute course of bilateral rTMS. Interventions: participants were randomly assigned at a 1:1 ratio to receive right dorsolateral prefrontal 1-Hz rTMS (24 weekly sessions; 120% of the resting motor threshold, 900 pulses in 15 minutes) or 24-week maintenance treatment with lithium pharmacotherapy. Participants were maintained on the same venlafaxine dose (150-225 mg/d) as the acute-phase dose. Main outcomes and measures: The primary outcome was the between-group difference in baseline-adjusted Montgomery-Åsberg Depression Rating Scale (MADRS) scores (range, 0-60, where 0 indicates no symptoms and 60 indicates most severe symptoms) at week 24, which was analyzed using a linear mixed-effects model for repeated measures in an intention-to-treat sample. The secondary outcome was the time to relapse (defined as a MADRS score ≥22), which was analyzed using Kaplan-Meier survival curves. Adverse events were also compared between groups. Results: among the 75 participants, 38 were assigned to the rTMS group (mean [SD] age, 44.1 [11.7] years; 21 male participants [55.3%]; baseline mean [SD] MADRS score, 8.9 [4.7]), and 37 were assigned to the lithium group (mean [SD] age, 44.1 [11.1] years; 19 male participants [51.4%]; baseline mean [SD] MADRS score, 7.9 [4.5]). There was no significant between-group difference in the primary outcome at week 24 (0.3 points [95% CI, -2.7 to 3.3 points]; P = .84). Survival analysis showed no meaningful between-group difference in relapse rates. During the 24-week maintenance phase, there were 7 patients who relapsed in each group. There was a higher number of adverse events among participants in the lithium group (n = 16) than in the rTMS group (n = 3; odds ratio, 7.10 [95% CI, 1.84-27.49]; P = .005). Conclusions and relevance: in this randomized clinical trial, low-frequency rTMS of the right prefrontal cortex as maintenance treatment showed comparable efficacy, as well as better safety and tolerance, compared with lithium. Maintenance low-frequency rTMS could be a promising relapse prevention strategy for patients with TRD.

Patologie/Applicazioni:

• Depressione
• Stimolazione Magnetica Transcranica (TMS)

Anno:

2025

Tipo di pubblicazione:

Articolo

Parola chiave:

rTMS; stimolazione magnetica transcranica; depressione maggiore; depressione resistente

Testata scientifica:

Jama Network

Mese:

06

Nota:

Il presente studio clinico randomizzato (MAINT-R trial) ha valutato l'efficacia e la tollerabilità del trattamento di mantenimento con stimolazione magnetica transcranica ripetitiva (rTMS) a bassa frequenza (1 Hz) applicata alla corteccia prefrontale dorsolaterale destra, confrontandola con la terapia farmacologica a base di litio, nella prevenzione delle ricadute in pazienti affetti da depressione resistente al trattamento (TRD) che avevano risposto positivamente a un trattamento acuto con rTMS bilaterale. I risultati dimostrano che il trattamento di mantenimento con rTMS è comparabile al litio in termini di efficacia clinica, come evidenziato dall’assenza di differenze significative nei punteggi della Montgomery-Åsberg Depression Rating Scale (MADRS) a 24 settimane (differenza media aggiustata: 0,3 punti; P = .84), e nei tassi di ricaduta (7 casi per gruppo). Tuttavia, il profilo di sicurezza del rTMS si è rivelato nettamente più favorevole, con un’incidenza significativamente inferiore di eventi avversi rispetto al litio (3 vs 16 eventi; OR = 7.10; P = .005). Tali evidenze supportano l’utilizzo del rTMS a bassa frequenza come opzione terapeutica sicura, ben tollerata e non inferiore al litio nel trattamento di mantenimento della TRD.

DOI:

10.1001/jamanetworkopen.2025.15881