South Florida Psychiatrist, Dr. Gregory Marsella Uses Priming Variation of rTMS as an alternative treatment for Depression and Stroke at the Chrysalis TMS Institute.
Priming Stimulation Enhances the Effectiveness of Low-Frequency Right Prefrontal Cortex Transcranial Magnetic Stimulation (TMS) in Major Depression
Paul B. Fitzgerald, MBBS, MPM, PhD, FRANZCP,* Kate Hoy, BBNSc (Hons),* Susan McQueen, RN, RPN (Nursing),* Sally Herring, BA (Hons),* Rebecca Segrave, BSci (Hons),* Greg Been, MBBS,* Jayashri Kulkarni, MBBS, MPM, PhD, FRANZCP,* and Zafiris J. Daskalakis, MD, PhD, FRCP(C)
Major depressive disorder is a severe illness resulting in significant disability and morbidity. It is well recognized that a significant percentage (~30%) of patients with depression fail to respond to standard therapies. More than 80% of patients treated conventionally (with multiple medications, lithium or thyroid hormone augmentation, electroconvulsive treatment) and followed up for 2 years do not remit. Of late, there have been a considerable number of trials of repetitive transcranial magnetic stimulation (rTMS) conducted in patients with treatment-resistant depression (TRD).Most of these trials used left prefrontal cortex high-frequency rTMS (between 5 and 20 Hz). An alternative rTMS paradigm involves the application of single or multiple long trains of low-frequency pulses (1 Hz) to the right prefrontal cortex. The first study of this sort showed that this was superior to placebo stimulation in treatment-responsive patients. A number of studies have subsequently assessed the efficacy of this type of stimulation in TRD. First, we found that it appeared to have similar efficacy to high frequency (TMS) stimulation applied to the left prefrontal cortex, a finding which has since been replicated. In addition, a recent study has shown a therapeutic benefit of low frequency, right-sided TMS stimulation over that of placebo rTMS. Finally, in a large sample of 130 patients, we found no difference in response between 1- and 2-Hz, right-sided TMS stimulation, with both resulting in a significant degree of clinical benefit (response rate of approximately 50%).
Despite the promising findings in rTMS studies of both right- and left-sided stimulation, concerns continue to be raised as to whether the effects seen with rTMS are clinically relevant and applicable to practice, in particular whether a sufficient percentage of patients respond to treatment. In this context, it seems important to develop methods to enhance response rates to rTMS treatment and the degree of response experienced by individual patients. There are a number of potential ways to do this. These include optimizing pulse number and intensity, treatment duration, developing ways to select appropriate patients, and the development of novel stimulation methods. In regard to the latter option, it is widely believed that low-frequency TMS works through the induction of a reduction in local brain activity. Research has suggested there may be a way to induce a greater depressant effect on cortical excitability than with standard, low-frequency TMS stimulation alone. This approach, referred to as priming stimulation, involves providing low-frequency TMS stimulation, for example, 1 Hz for 10 to 15 minutes. However, the low-frequency train is preceded by a period of high frequency TMS stimulation provided at low intensity. This priming condition has been shown to markedly enhance the neural response to the low-frequency TMS stimulation train. To date, priming stimulation has only been explored in neurophysiological experiments, and the effect of this approach in the treatment of depression or other psychiatric disorders has not been studied.
Therefore, the current study was designed to investigate whether priming stimulation would enhance therapeutic response to low-frequency, right-sided rTMS in patients with TRD. To do this, we conducted a double-blind trial comparing priming stimulation (active, low-intensity, high-frequency TMS stimulation followed by active, standard, low frequency stimulation) to a placebo-priming stimulation condition (placebo, low-intensity, high-frequency TMS stimulation followed by active, standard, low-frequency TMS stimulation) in the group of 60 patients with TRD. We hypothesized that the group receiving active-priming TMS stimulation would achieve a greater clinical response than patients in the placebo-priming stimulation group.
In conclusion, priming pre-stimulation with subthreshold 6-Hz rTMS appears to significantly enhance response to right-sided, low-frequency rTMS. Priming stimulation was well tolerated and practical and presents as a potentially viable future clinical alternative for the application of rTMS in clinical practice. Further studies are required to confirm the efficacy of priming stimulation and to explore whether this form of stimulation acts through the priming of synaptic transmission or through a simpler additive dose effect.