Although a growing number of studies are exploring the efficacy of rTMS for depression, few studies have evaluated its use for the treatment of schizophrenia. Schneider, who is affiliated with the David Geffen School of Medicine at the University of California, Los Angeles, through its San Fernando Valley Veterans Affairs Medical Center affiliate and is the research director at Gateways Hospital in Los Angeles, said he and colleagues are nearing completion on two double-blind studies investigating adjunctive use of rTMS for the treatment of such negative symptoms as restricted affect, diminished social drive and lack of volition in patients with schizophrenia. All patients continue to receive their atypical antipsychotics during treatment.
In one study, funded by the National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD), 34 patients are randomized to either active rTMS or sham treatment for two weeks, five days per week. In the second study, funded by Stanley Medical Research Institute, 51 patients are randomized to 1 Hz, 10 Hz or sham treatment for four weeks, five days per week. In each study, patients are also seen one month posttreatment to assess any carryover effects. In addition, Schneider and colleagues are studying effects on hearing threshold after longer-term TMS exposure.
"We also have an open-label component where they can come in for 'maintenance' treatment," Schneider said, adding that nobody really has a firm grasp on the concept of maintenance treatment in TMS. The maintenance treatment is once every two weeks.
The patients in active treatment receive rTMS of the dorsolateral prefrontal cortex. We get there by activating the motor strip in their head, which produces a twitching in the hand, Schneider said. The dorsolateral prefrontal cortex, he added, is thought to control negative symptoms as well depressive symptoms. It is the same area that has been used in prior TMS trials to treat major depression.
Repetitive transcranial magnetic stimulation can be beneficial in schizophrenia, Schneider believes, possibly through a reversal of pre-existent or iatrogenically produced hypofrontality. This is the rationale for the use of only newer-generation atypical antipsychotics in his studies.
Outcome measures include the Scale for the Assessment of Negative Symptoms (SANS), the Wisconsin Card Sort Test (WCST) and the SF-36 Quality of Life questionnaire, which the patient fills out.
"From our initial analysis on NARSAD data, treatment clearly separates from placebo in terms of the [WCST] and SANS," Schneider said. He added that the study criteria allowed patients to enter with some positive symptoms as measured by the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Symptom Scale (PANSS).