title: Theta Burst Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations: Negative Findings From a Double-Blind-Randomized Trial.
abstract: BACKGROUND
  Auditory verbal hallucinations (AVH) in schizophrenia are resistant to antipsychotic medication in approximately 25% of patients. Treatment with repetitive transcranial magnetic stimulation (rTMS) for refractory AVH has shown varying results. A stimulation protocol using continuous theta burst rTMS (TB-rTMS) showed high efficacy in open label studies. We tested TB-rTMS as a treatment strategy for refractory AVH in a double-blind, placebo-controlled trial.
  
  
  METHODS
  Seventy-one patients with AVH were randomly allocated to TB-rTMS or placebo treatment. They received 10 TB-rTMS or sham treatments over the left temporoparietal cortex in consecutive days. AVH severity was assessed at baseline, end of treatment and follow-up using the Psychotic Symptom Rating Scale (PSYRATS) and the Auditory Hallucinations Rating Scale (AHRS). Other schizophrenia-related symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS).
  
  
  RESULTS
  Seven patients dropped out before completing the study. In the remaining 64, AVH improved significantly after treatment in both groups as measured with both PSYRATS and AHRS. PANSS positive and general subscores also decreased, but the negative subscores did not. However, improvement did not differ significantly between the TB-rTMS and the placebo group on any outcome measure.
  
  
  CONCLUSIONS
  Symptom reduction could be achieved in patients with medication-resistant hallucinations, even within 1 week time. However, as both groups showed similar improvement, effects were general (ie, placebo-effects) rather than specific to treatment with continuous TB-rTMS. Our findings highlight the importance of double-blind trials including a sham-control condition to assess efficacy of new treatments such as TMS.
authors.affiliation: Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands; Brain Center Rudolf Magnus, Utrecht, The Netherlands s.koops@umcutrecht.nl.
authors.forename: Sanne
authors.initials: S
authors.lastname: Koops
authors.affiliation: Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands; Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: van Dellen
authors.affiliation: Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands; Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: Maya J L
authors.initials: MJ
authors.lastname: Schutte
authors.affiliation: Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands; Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Nieuwdorp
authors.affiliation: Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands; Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: Sebastiaan F W
authors.initials: SF
authors.lastname: Neggers
authors.affiliation: Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands; Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: Iris E C
authors.initials: IE
authors.lastname: Sommer
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006212:Hallucinations / Q000523:psychology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe; D015990:Placebo Effect; D012559:Schizophrenia / Q000628:therapy*; D012565:Schizophrenic Psychology; D013702:Temporal Lobe; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
keywords: RCT; TMS; focal stimulation; psychotic disorder; voices