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Consensus statement for the treatment of depression with rTMS

Since mid-2017 the treatment of therapy resistant depressions with repetitive transcranial magnetic stimulation (rTMS) in combination with cognitive behavioral therapy is eligible for reimbursement in The Netherlands. However, guidelines for the application of rTMS are not available. 
 
To achieve the development of such guidelines the Stichting Hersenstimulatie and the Nederlands Kenniscentrum Angst en Depressie (NedKAD) collaborated to draft a consensus statement. A summary of this consensus statement can be found on this page. 
 
The available evidence and two expert meetings have lead the aforementioned parties to reach four recommendations regarding the treatment of depression with rTMS:
1. High-frequency rTMS (HF rTMS; 10-20 Hz) over the left dorsolateral prefrontal cortex (L-DLPFC) has an antidepressant effect .
2. Low-frequency rTMS (LF rTMS; ≤ 1 Hz) over the right dorsolateral prefrontal cortex (R-DLPFC) has an antidepressant effect. 
3. The effectiveness of HF rTMS over the L-DLPFC is comparable to that of LF-rTMS on the R-DLPFC 
4. An additive effect of rTMS over the DLPFC is found on antideppessant medication.
 
The conclusion of both bodies is that rTMS has not only been proved effective in double-blind placebo-controlled studies and meta-analysis thereof, but that the effects can also be generalized to large groups from multiple centers. The effects over a period of 6 to 12 months can be maintained in a majority of patients, whether or not using maintenance rTMS.
 
Safety and side effects
On the basis of recommendations made by Rossi et al (2009) the consensus statement includes suggestions for the frequency of stimulation (Hz), the intensity of the stimulation (as a percentage of the motor threshold (MT)), the duration of a drive train, and risk factors that need to be taken into account. These suggestions are made to minimize the chance of epileptic seizures caused by rTMS, which according to research literature is 0.007% (20 seizures / 300,000 sessions) and according to clinical practice is 0.003% (7 seizures / 250,000 sessions).
In general, rTMS is considered although it should be noted that HF rTMS is more risky than LF rTMS. However, when the stimulation parameters suggested by Rossi et al. are taken into account, the application of rTMS is safe if the parameters portrayed in the table on the right hand side are taken into account. 
 
Stimulation parameters
An intensity of 110-120% of the MT, a frequency of either 1, 10 or 20 Hz, and a total number of stimuli of 1200-3000 per treatment appears to have the most beneficial effect in the treatment of depression. With LF rTMS, usually continuous stimulation without intertrain interval is used while HF rTMS usually applies an intertrain interval of 25-60 seconds. 
 
Coil orientation
The orientation of the TMS coil can make a big difference in the effect of stimulation. Research has shown that an angle of 45 degrees is the only orientation that causes a measurable blood oxygenation response. Therefore, the recommendation for the coil orientation in rTMS treatment of depression is also 45 degrees with respect to the midline.
 
Conclusion
The treatment of a major depressive disorder with rTMS is effective and safe in patients who have attempted at least 1 adequate session with antidepressants and psychotherapy. Future research should point out whether rTMS can also be used even before considering antidepressant medication.
 
  • M. Arns, C. Bervoets, P. Van Eijndhoven,C. Baeken, O.A. Van Den Heuvel, A. Aleman, D.J.L.G Schutter, Y. Van Der Werp, S. Van Belkum, I.E. Sommer, R. Van Ruth, B. Haarman, J. Spijker, A.T. Sack. Consensusverklaring voor de otepassing van rTMS bij depressie in Nederland en België. Tijdschrift voor de psychiatrie 2019; 61:6:411-420
  • Rossi S, Hallett M, Rossini, PM, PascualLeone A,The Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 2009;120: 2008-39