No place in France for repetitive transcranial magnetic stimulation in the therapeutic armamentarium of treatment-resistant depression?

TY - JOUR

T1 - No place in France for repetitive transcranial magnetic stimulation in the therapeutic armamentarium of treatment-resistant depression?

AU - Batail, Jean Marie

AU - Gaillard, Raphaël

AU - Haffen, Emmanuel

AU - Poulet, Emmanuel

AU - Sauvaget, Anne

AU - Szekely, David

AU - Brunelin, Jérôme

AU - Bulteau, Samuel

AU - Bubrovszky, Maxime

AU - Smadja, Julien

AU - Bourla, Alexis

AU - Bouaziz, Noomane

AU - Januel, Dominique

AU - Rotharmel, Maud

AU - Arns, Martijn

AU - Downar, Jonathan

AU - Fitzgerald, Paul B.

AU - Brunoni, André R.

AU - Pallanti, Stefano

AU - D'Urso, Giordano

AU - Baeken, Chris

AU - Williams, Nolan R.

AU - Millet, Bruno

AU - Lefaucheur, Jean Pascal

AU - Drapier, Dominique

N1 - Funding Information: There are significant methodological weaknesses in the HAS work which limits the relevance of their conclusions. The overall rationale behind including only 8 studies in regards to the incredibly rich available data in the literature is at best unclear if not confusing. Moreover, not all of these studies were designed to test superiority of active rTMS over sham. One study [1] had a significant proportion of highly comorbid patients (post-traumatic stress disorder, substance abuse, neurological disorder). In 6/8 studies, the sham technique (90° tilted coil) was known to be inappropriate because potentially active [2]. Finally, the included studies were heterogeneous in terms of methodological quality, particularly concerning the co-prescription of AD medication and treatment resistance severity. Then, the HAS meta-analysis, based on studies with restrictive inclusion criteria and reporting a very small proportion of currently available data, but with a highly variable set of designs and participants, does not reflect the reality of the rTMS practice neither in France nor internationally. Most importantly, the time window chosen for their meta-analytic work is questionable since it does not include any TMS study prior to 2017, thereby excluding the most well-powered and well-designed pivotal trials in the field such as the pivotal Neuronetics trial that resulted in FDA approval and the independent NIH-funded replication of that trial [3,4]. The conclusion of the HAS analysis therefore seems inappropriate and suffers from obvious lack of representativeness. Thus, the work of the HAS did not meet the reference standards for meta-analyses, as required for registration in PROSPERO or PRISMA databases. Evidence of rTMS efficacy has been reported reproducibly in large randomized clinical trials [3,4], naturalistic studies [5], and meta-analyses [6], regardless of the device used to perform prefrontal rTMS. Safety has also been demonstrated [7] and it is certain that rTMS produces less side effects than drugs [8]. Contrary to what has been stated by the HAS, rTMS can be cost-effective from a medico-economic point of view if we consider the potential benefits of effective management of depression on direct (less medications, fewer hospitalizations) and indirect (improvement of professional functioning) cost-savings, rather than considering only the economic burden of the technique. The cost-effectiveness ratio was evaluated in a meta-analysis which concluded in favor of rTMS over medications [9]. As it stands, the HAS report raises serious concerns in terms of access to care and ethical issues. By not recommending rTMS for the treatment of TRD, the HAS decision therefore exposes France to serious consequences. Firstly, such a decision discredits an entire field of clinical activity based for years on this therapeutic innovation in the domain of psychiatry and depression and may cause patients and their families to lose a potentially valuable treatment option. Secondly, not recommending the therapeutic practice of rTMS in a structured way exposes the risk of heterogeneous and uncontrolled practice without any guarantee of quality and regulation. This point is a crucial issue because official recognition, by such a regulatory agency, could require the establishment of a sub-specialty of practitioners properly trained in neuromodulation therapy with high expected benefits for patients and therefore for public health [10]. Thirdly, it will handicap France in this promising field of clinical research which is rapidly evolving internationally. For nearly 20 years, and not being limited to the last 5 years as HAS done, the scientific literature has provided sufficient data on the efficacy, safety, cost-effectiveness of prefrontal rTMS in the treatment of TRD to be considered as a relevant therapeutic option. Although, there is ongoing research on new stimulation paradigms, including multi-daily sessions, which may provide greater and longer lasting benefit, the efficacy of conventional high-frequency rTMS of the left DLPFC should be considered sufficient to validate this technique as a therapeutic option and not as a technique in development. There is an urgent need to revise this position of health regulatory agencies in France.

PY - 2023/5/1

Y1 - 2023/5/1

UR - http://www.scopus.com/inward/record.url?scp=85161077905&partnerID=8YFLogxK

U2 - 10.1016/j.brs.2023.05.015

DO - 10.1016/j.brs.2023.05.015

M3 - Letter

C2 - 37245843

AN - SCOPUS:85161077905

SN - 1935-861X

VL - 16

SP - 927

EP - 929

JO - Brain Stimulation

JF - Brain Stimulation

IS - 3

ER -