Repetitive Transcranial Magnetic Stimulation for Negative Symptoms of Schizophrenia: a Randomized Controlled Pilot Study

Background: Negative symptoms in schizophrenia are associated with deficits in executive function and frequently prove highly resistant to neuroleptic medication. Using repetitive transcranial magnetic stimulation (rTMS) to activate the prefrontal cortex has been suggested as a treatment for negative symptoms.

Methods: We performed a double-blind randomized controlled pilot study of real versus sham rTMS for negative symptoms in schizophrenia. 17 right-handed patients with prominent negative symptoms (PANSS negative subscore >or=20) were randomized to a 10 day course of real (n=8) or sham rTMS (n=9) applied to the left dorsolateral prefrontal cortex (20 trains per day, 10 s treatment at 10 Hz, 50 s inter-train interval, 110% of motor threshold). The primary outcome measure was PANSS negative symptom score. Secondary outcomes included mood, cognitive function and side-effects. Patients were followed-up two weeks afterwards. The main effect of treatment arm was evaluated across end of treatment and two-week follow-up time points using ANCOVA.

Results: All subjects completed the treatment course. There was no significant difference between the two groups on PANSS negative symptom scores at either time point. At the end of treatment, no subjects in either group met the criterion for response (i.e. a 20% reduction in baseline PANSS negative symptom score). The real rTMS group had better delayed recall on a test of verbal learning than the sham group at 2 week follow-up.

Conclusions: Real rTMS was not found to be better than sham rTMS in alleviating negative symptoms of schizophrenia although it was associated with some improvement in aspects of cognitive function at follow-up.