Magnetic seizure therapy of major depression.

E lectroconvulsive therapy (ECT) plays an important role in the treatment of severely depressed patients, especially those who do not respond to antidepressant medications. However, its cognitive adverse effects restrict its use. The dosage of the electrical stimulus and the anatomic placement of stimulating electrodes are critical in determining the efficacy and cognitive adverse effects of ECT. Nonetheless, with ECT, control over the spatial distribution and magnitude of intracerebral current density is limited by high skull impedance, which shunts most of the electrical stimulus through the scalp and cerebrospinal fluid. There are also individual differences in skull anatomy that result in uncontrolled variation in intracerebral current density. Repetitive transcranial magnetic stimulation (rTMS) may provide a more precise method of seizure induction; rTMS induces currents in the cerebral cortex through rapidly alternating magnetic fields. Magnetic fields penetrate the scalp and skull with no resistance, offering greater control over the site of seizure initiation and extent of cortical stimulation. We recently reported the induction of generalized seizures in nonhuman primates under anesthesia using a custom modified magnetic stimulator that matched the peak induced voltage achieved with electroconvulsive shock. We report the first trial to our knowledge of magnetic seizure induction under general anesthesia in a psychiatric patient. The patient provided informed consent to undergo magnetic seizure induction for her first 4 treatments, followed by conventional ECT, under a protocol approved by the Institutional Review Board of the State of Bern, Switzerland. The patient, a 20-year-old woman, had a 3-year episode of major depression, and treatment failed in trials using a selective serotonergic reuptake inhibitor, 2 tricyclic antidepressants, 2 monoamine oxidase inhibitors, and several newer agents. She also did not respond to augmentation with lithium, triiodothyronine, and methylphenidate. Each trial achieved adequate doses for periods greater than 6 weeks, but her level of functioning remained impaired. Physical and neurological examinations, admission laboratory analysis results, findings from electrocardiogram, and brain computed tomographic scans were unremarkable. Magnetic seizure therapy (MST) sessions were conducted under general anesthesia 3 times per week for 4 treatments. Electroencephalogram (EEG) and electrocardiogram results, pulse oximetry, and blood pressure were monitored. Etomidate (0.3 mg/kg intravenously) was used as the anesthetic agent for the first 2 treatments, as this is the standard ECT anesthetic used at this center (University Hospital of Bern). Etomidate has been reported to have proconvulsant properties. The 2 subsequent treatments were performed with thiopental anesthesia (5 mg/kg intravenously) to establish capacity for seizure induction using a standard short-acting barbiturate anesthetic. Succinylcholine (1 mg/kg) was used for muscle relaxation, and the patient was ventilated with positive pressure 100% oxygen. The EEG electrodes (frontomastoid) were slotted to prevent heating from magnetic stimulation, and the patient wore earplugs to protect hearing. Treatments were delivered with a custom-modified magnetic stimulator (Magstim Super Rapid; Magstim Company Ltd, Whitland, Wales) that had a broader pulse width and more charging units than commercially available devices, permitting stimulation up to 40 Hz at peak intensity. The rTMS was administered with a precooled, double-cone coil held at the vertex or a figure 8 coil on the right prefrontal cortex (Table). Eachof theMSTtrialsproducedatonicoclonicseizure (from30-270seconds),documentedbybothmotorandEEG manifestations.Themagneticseizure thresholdwastitrated at the second session by administering trains of increasing duration until a seizure was induced. Generalized seizures characteristic of ECT were reliably obtained with stimulation at 40 Hz, 100% of maximal stimulator output, administered for 4 seconds. Each treatment was well tolerated. After the fourth treatment, the Hamilton Rating Scale for Depression score decreased to 13 from a baseline of 20. The MiniMental State score remained unchanged at 30 throughout the treatment course. Following the MST sessions, the patient received 8 conventional ECT treatments (right unilateral, 200% above initial seizure threshold), and had a final posttreatment Hamilton Rating Scale for Depression score of 6. This case demonstrates that magnetic seizure induction under general anesthesia is feasible in the treatment of psychiatric disorders. Recent brain imaging studies suggest that manipulations of ECT electrode placement and electrical dosage that are associated with greater efficacy produce more robust functional changes in prefrontal cortex. The enhanced control over both dosage and focality of stimulation that may be achieved with MST offers the capacity to restrict seizure induction to specific cortical areas, such as prefrontal cortex regions, LETTERS TO THE EDITOR