Magnetic Seizure Therapy

If the axiom that a seizure is necessary to obtain antidepressant effects holds true, the current mode of seizure induction needs to improve. The retrograde/anterograde amnesia due to nonintended passage of electricity through the hippocampus limits the widespread use of ECT. ECT research has gone through many refinements including electrode placements, intensity of stimulation, and waveforms applied. Current research in brief and ultrabrief pulses is an effort to increase the efficacy and decrease the cognitive impairment (Sackeim et al., 2002c). Another line of research aimed at delivering ECT more focally and reducing cognitive side effects uses magnetic fields rather than electric fields to induce seizures. Control over intracerebral current density and its spatial distribution (although improved with anterior electrode placement to target prefrontal and closely related subcortical networks) can be achieved using high oscillating magnetic fields (Lisanby et al., 2001b). Unlike electricity, magnetic fields pass unimpeded through skull and soft tissue and can be applied more focally than electricity. Magnetic convulsive therapy may offer the possibility of fewer cognitive side effects and perhaps an equal therapeutic efficacy to ECT.

It took over 10 years for researchers at Columbia University to develop such a technology (Sackeim, personal communication, May 2001). Lisanby and Sackeim custom-designed a transcranial magnetic stimulator (TMS) that can deliver fast trains of four times the electromyographic threshold and succeeded in inducing generalized seizures in nonhuman primates. Commercially available TMS machines have shorter pulse width and lower charging capacity and were unsuccessful in reproducibly inducing seizures (George et al., 1999) [see TMS section for more technical details and the safety implication for repetitive TMS (rTMS)]. Lisanby and Sackeim proposed the following: "The enhanced control over dosage and focality achieved with rTMS may offer the capacity to focus seizure induction in the prefrontal cortex, thereby improving the efficacy and limiting the cognitive side effects due to medial temporal lobe stimulation."

Lisanby and colleagues, working with Dr. Thomas Schlaepfer in Berne, Switzerland, applied this technology to induce four separate magnetically induced seizures in a depressed patient under general anesthesia (Lisanby et al., 2001b). The trains of stimulation were delivered at 40 Hz, 100 percent of maximal stimulator output (40 percent greater than commercially available TMS), administered for 4 sec. Although the researchers reported an improvement in depressive symptoms, the role of this method as a potential treatment for various neuropsychiatric conditions (including depression) remains to be proven.

As a first step, and under special Investigational Device Exemption (IDE) from the FDA, the safety and side effects of MST are currently being tested. It will first be tried in depressed patients who are undergoing a regular course of ECT, and then it will be tested as a stand-alone procedure. Clinical trials will likely follow. Compared with ECT, MST has the theoretical ability to be more circuit-based in that the region of brain where the seizure initiates can be more focally activated. However, as a potential therapy, this technique still depends on causing a generalized seizure and requires repeated episodes of general anesthesia. The other forms of device-based therapies do not rely on seizures and are thus theoretically less toxic. Whether a generalized seizure is required for brain stimulation technology to have its antidepressant effect has been a matter of intense debate. As discussed in subsequent sections, data from TMS (Nahas et al., 2001a; McNamara et al., 2001) and perhaps VNS (Rush et al., 2000) suggest that some forms of neural stimulation can treat depression without invoking generalized seizures, which are required with ECT.

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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