ECT and rTMS- Not Better Together

Out on PubMed, from investigators in Aarhus and Glostrup, Denmark is this pilot clinical trialLow frequency rTMS, inhibits the antidepressive effect of ECT. A pilot study.

Buchholtz PE, Ashkanian M, Hjerrild S, Hauptmann LK, Devantier T, Jensen P, Wissing S, Thorgaard M, Speed M, Brund RBK, Videbech P.Acta Neuropsychiatr. 2020 Jul 27:1-27. doi: 10.1017/neu.2020.28. Online ahead of print.PMID: 32713367

The abstract is copied below:

Objective: Low frequency rTMS of the prefrontal cortex have been shown to have a statistically and clinically significant antidepressant effect. The present pilot study was carried out to investigate if right prefrontal low frequency rTMS as an add-on to ECT accelerates the antidepressant effect and reduces cognitive side effects.
Methods: In this randomized, controlled, double blind study thirty-five patients with major depression were allocated to ECT+placebo or ECT+ low frequency right prefrontal rTMS. The severity of depression was evaluated during the course using the Hamilton scale for depression (the 17-item as well as the 6-item scale) and the Major Depression Inventory. Furthermore, neuropsychological assessment of cognitive function was carried out.
Results: The study revealed no significant difference between the two groups for any of the outcomes, but with a visible trend to lower scores for MDI after treatment in the placebo group. The negative impact of ECT on neurocognitive functions was short lived and scores on logical memory were significantly improved compared to baseline 4 weeks after last treatment. The ECT-rTMS group revealed generally less impairment of cognitive functions than the ECT-placebo group.
Conclusion: The addition of low frequency rTMS as an add-on to ECT treatment did not result in an accelerated response. On the contrary, the results suggest that low frequency rTMS could inhibit the antidepressant effect of ECT.

And from the text:

(Introduction)

The antidepressant effect of rTMS does not involve seizures, but like ECT low frequency rTMS has been shown to inhibit amygdala-kindled seizures in animal studies. Therefore, theoretically it is possible that low frequency rTMS can amplify and thus accelerate the antidepressant effect of ECT.

(Discussion)

The antidepressant effect of right prefrontal low frequency rTMS has been substantiated in previous RCTs and meta-analysis (Klein et al.1999, Fitzgerald et al. 2006, Fitzgerald et al. 2007, Bares et al. 2009, Pallanti, et al. 2010, Brunelin et al. 2014). The trend towards a better outcome on the depression scale scores among patients receiving placebo as add-on to ECT is therefore surprising. Naturally, this could be a chance finding, but as the study was underpowered, one cannot preclude that the inferiority of rTMS as add-on in this study is actually underestimated. 

The hope of additive, even synergistic, antidepressant effect of these two modalities was not borne out. The idea that the inhibitory (anticonvulsant) effect of rTMS did not add benefit to ECT (potently anticonvulsant) but rather interfered with its antidepressant efficacy, is theoretically interesting, but likely fantastical.

Interesting features of this paper include the use of both the HAM-D17 and the HAM-D6 and some of the characteristics of the ECT: age-based dosing on a device with maximum 1008 mC output, a pulse width of 1.0-2.0 ms and the potential for switch to bilateral electrode placement for slow response.

These investigators are to be congratulated for carrying out this interesting, albeit negative, study.