High-Frequency Prefrontal Repetitive Transcranial Magnetic Stimulation for the Negative Symptoms of Schizophrenia

Abstract

The negative symptoms of schizophrenia are difficult to treat and are predictors of poor outcome. New somatic treatments are needed to reverse these symptoms and improve function. One promising approach is repetitive transcranial magnetic stimulation (rTMS), although results to date have been mixed. This pilot study assessed higher doses of rTMS and assessed particular demographic factors that may influence treatment response. Five patients with schizophrenia or schizoaffective disorder enrolled to receive 20 sessions of rTMS administered with a Magstim Super Rapid device (The Magstim Company Ltd, Wales, UK). Treatment was administered at 20 Hz for 2 seconds, intertrain interval of 28 seconds, and at 100% motor threshold to the left dorsolateral prefrontal cortex in an open-label pilot study. Positive and Negative Syndrome Scale symptom assessments occurred at 2-week intervals during treatment and twice at 4-week intervals after termination. Treatments were well tolerated with no adverse events. One patient withdrew from the study in the setting of medication noncompliance. Of the patients who completed treatment, 2 had reductions in positive symptoms by 9% and 26%, maintained at 1 month. A third patient had a 14% reduction in negative symptoms at week 4, and a fourth patient had a 55% reduction at week 4. Negative symptom improvement was not related to depressive or extrapyramidal symptoms, which were unchanged with treatment. This pilot study of rTMS treatment for the negative symptoms of schizophrenia is promising with respect to safety and feasibility. The promising preliminary evidence for improvements in this open-label setting should be followed up with a randomized clinical trial to establish efficacy. Further work may explore the potential utility of rTMS for the otherwise largely untreatable negative symptoms, which account for so much of the morbidity of schizophrenia.