title: Can low-frequency repetitive transcranial magnetic stimulation really relieve medication-resistant auditory verbal hallucinations? Negative results from a large randomized controlled trial.
abstract: BACKGROUND
  Several studies have applied low-frequency repetitive transcranial magnetic stimulation (rTMS) directed at the left temporoparietal area (TP) for the treatment of auditory verbal hallucinations (AVH), but findings on efficacy are inconsistent. Furthermore, recent functional magnetic resonance imaging (fMRI) studies indicate that the left TP is not a general focus of activation during the experience of AVH. The aims of this study are twofold: to investigate the effects of rTMS on AVH in a double blind, randomized, sham-controlled study; and to investigate whether the efficacy can be improved when rTMS is guided by individual fMRI scans of hallucinatory activation.
  
  
  METHODS
  Sixty-two patients with medication-resistant AVH were randomized over three conditions: rTMS targeted at the area of maximal hallucinatory activation calculated from individual fMRI scans during AVH, rTMS directed at the left TP, and sham treatment. Repetitive TMS was applied during 15 sessions of 20 min each, at 1 Hz and 90% of the individual motor threshold. The severity of AVH and other psychotic symptoms were monitored during treatment and 3-month follow-up, with the Auditory Hallucination Rating Scale, the Positive and Negative Syndrome Scale, and the Psychotic Symptom Rating Scales.
  
  
  RESULTS
  The effects of fMRI-guided rTMS and left TP rTMS on the severity of AVH were comparable to those of sham treatment. No differences in severity of general psychotic symptoms were found among the three treatment conditions.
  
  
  CONCLUSIONS
  Low-frequency rTMS administered to the left TP or to the site of maximal hallucinatory activation is not more effective for medication-resistant AVH than sham treatment.
authors.affiliation: Parnassia Bavo Psychiatric Institute, Lijnbaan 4, The Hague, The Netherlands. c.slotema@psyq.nl
authors.forename: Christina W
authors.initials: CW
authors.lastname: Slotema
authors.forename: Jan Dirk
authors.initials: JD
authors.lastname: Blom
authors.forename: Antoin D
authors.initials: AD
authors.lastname: de Weijer
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Diederen
authors.forename: Rutger
authors.initials: R
authors.lastname: Goekoop
authors.forename: Jasper
authors.initials: J
authors.lastname: Looijestijn
authors.forename: Kirstin
authors.initials: K
authors.lastname: Daalman
authors.forename: Anne-Marije
authors.initials: AM
authors.lastname: Rijkaart
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.forename: Hans W
authors.initials: HW
authors.lastname: Hoek
authors.forename: Iris E C
authors.initials: IE
authors.lastname: Sommer
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D006212:Hallucinations / Q000523:psychology / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000523:psychology / Q000628:therapy; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents