Major depression is a common mental health problem and associated with significant morbidity and mortality, including impaired social and physical functioning and increased risk for suicide. Electroconvulsive therapy (ECT) is highly efficacious in treatment-resistant depressive disorders, but cognitive side effects are frequently associated with the treatment. Magnetic seizure therapy (MST) is a form of convulsive therapy, using magnetic fields in order to induce therapeutic seizures. First studies suggested that cognitive side effects of MST, including postictal recovery time, are more benign than those resulting from ECT treatment. In this open-label study we tested the hypothesis that MST is associated with clinically significant antidepressant effects in treatment-resistant depression (TRD) as an add-on therapy to a controlled pharmacotherapy.
Twenty patients suffering from TRD were randomly assigned to receive either MST or ECT starting from July 2006 until November 2008. Primary outcome measure was antidepressant response assessed by Montgomery Åsberg Depression Scale. Secondary outcome measures included Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Beck Depression Inventory and 90-Item Symptom Checklist.
Antidepressant response (improvement of 50% in MADRS ratings) was statistically significant and of similar size in both treatment groups. Cognitive side effects were observed in neither group. Characteristics in MST- and ECT-induced seizures were comparable, especially regarding ictal activity and postictal suppression. Thus, MST may be a potential alternative to ECT if efficacy and safety are validated in larger clinical trials.
Major depression is widely recognized as the world’s most burdensome mental health problem in adults (Lopez and Murray, 1998). The disorder is associated with significant morbidity and mortality, including impaired social and physical functioning and increased risk for suicide (Agency for Health Care Policy and Research, 1993, Hirschfeld and Russell, 1997 and Wells et al., 1989). Treatment of depressive disorders – especially of treatment-resistant forms - is therefore an important focus of current psychiatric research. Presently available evidence-based treatments lead to symptomatic improvement in most patients. However, up to 40% of patients partially responding to antidepressant therapy suffer from clinically relevant residual symptoms (Fava and Davidson, 1996) and 30% of patient do not respond to four evidence-based treatment steps (Rush et al., 2006). The more treatments fail, and the longer a current depressive episode lasts, the higher is the risk of developing a so-called treatment-resistant depression (TRD) (Rau et al., 2007).
In an effort to find safer and more effective alternatives to antidepressant drugs for treating severe depression, investigators have recently examined a variety of non-pharmacologic modalities, e.g. electroconvulsive therapy (ECT) (Lisanby, 2007), repetitive transcranial magnetic stimulation (rTMS) (O’Reardon et al., 2007), vagus nerve stimulation (VNS) (Schlaepfer et al., 2008), deep brain stimulation (DBS) (Bewernick et al., 2010) and magnetic seizure therapy (MST) (George, 2002).
Electroconvulsive therapy was developed in 1938 and has been demonstrated to be highly efficacious in severely treatment-resistant depressive disorders, with more than half of patients achieving remission (Khalid et al., 2008). ECT is the most effective treatment for major depressive disorder (APA, 1994 and Ebmeier et al., 2006), but cognitive side effects such as amnesia are commonly reported (Datka et al., 2007, Donahue, 2000 and Schulze-Rauschenbach et al., 2005).
Some randomised trials with transcranial magnetic stimulation (rTMS) have suggested similar efficacy as ECT in the treatment of non-psychotic depression (Grunhaus et al., 2000, Grunhaus et al., 2003, Janicak et al., 2002 and Schulze-Rauschenbach et al., 2005), although no large comparison trials have been undertaken so far. The feasibility and safety of deliberately induced seizures with the help of repetitive magnetic fields was first demonstrated in non-human primates (Dwork et al., 2004, Kosel et al., 2003b and Lisanby et al., 2001b). One further alternative to ECT is magnetic seizure therapy (MST), a form of convulsive therapy, in which magnetic fields are used to induce therapeutic seizures. In the course of the first human proof-of-concept study, one patient received a course of four MST treatments (Lisanby et al., 2001b). The same group treated another patient successfully with a full course of 12 MST (Kosel et al., 2003a). In contrast to ECT, MST is a more focal form of convulsive therapy (Lisanby et al., 2001b) that targets seizure induction in prefrontal cortex and spares medial temporal structures (i.e. hippocampus), which are involved in the development of cognitive side effects of ECT (Kosel et al., 2003a, Lisanby et al., 2003a, Lisanby, 2002 and Moscrip et al., 2006). It has been demonstrated in primate models of MST that magnetically induced seizures are different from seizures induced by electrical convulsive stimulation (ECS) in regard to neurophysiological effects on the hippocampus (Lisanby et al., 2003a).
Only few results have been published since the first application of MST in the year 2000 (Lisanby et al., 2001b). Preliminary studies suggest that MST possesses antidepressant efficacy (Kayser et al., 2009 and White et al., 2006), good feasibility and better tolerability in comparison to ECT (Lisanby et al., 2003a). First studies have suggested a more benign cognitive side effects profile of MST as compared to ECT (Kayser et al., 2009, Kosel et al., 2003a and Lisanby et al., 2003b), including faster postictal recovery time (Kirov et al., 2008), reductions in attention deficits and anterograde and retrograde amnesia (Dwork et al., 2004, Khalid et al., 2008, Lisanby et al., 2003a and Moscrip et al., 2006).
In this study twenty patients were assigned to receive either complete courses of treatment with either MST or ECT. We hypothesized that MST would lead to clinically significant antidepressant effects in treatment-resistant depression (TRD), as an add-on treatment to a controlled drug therapy.
