title: Significant analgesic effects of one session of postoperative left prefrontal cortex repetitive transcranial magnetic stimulation: a replication study.
abstract: BACKGROUND
  In a recent preliminary trial in 20 patients after gastric bypass surgery, 20 minutes of repetitive transcranial magnetic stimulation (TMS) over the left prefrontal cortex was associated with a 40% reduction in postoperative patient-controlled morphine use. As is the case with all novel scientific findings, and especially those that might have an impact on clinical practice, replicability is paramount. This study sought to test this finding for replication and to more accurately estimate the effect size of this brief intervention on postoperative morphine use and postoperative pain and mood ratings.
  
  
  METHODS
  Twenty participants who underwent gastric bypass surgery completed this replication and extension study. Beck Depression Inventory and Center for Epidemiological Studies Depression scale scores were collected before surgery and at the time of discharge from the hospital. Immediately after surgery, participants were randomly assigned to receive 20 minutes of real or sham repetitive TMS (rTMS) (10 Hz, 10 seconds-ON, 20 seconds-OFF for a total of 4000 pulses). Patient-controlled morphine pump usage was tracked throughout each participant's postoperative hospital stay. In addition, pain and mood ratings were collected via visual analogue scales twice per day.
  
  
  RESULTS
  Findings from the original postoperative TMS trial were replicated, as cumulative morphine usage curves were significantly steeper among patients receiving sham TMS, and participants receiving real TMS had used 35% less morphine at the time of discharge than participants receiving sham TMS. At the time of discharge, subjects who had received real TMS had used 42.50 mg of morphine, whereas subjects receiving sham TMS had used an average of 64.88 mg. When the data from the original preliminary trial were combined with the data from this replication trial, a significant difference in cumulative morphine usage was observed between subjects receiving real and sham TMS. Overall, participants who received real TMS used 36% less morphine and had significantly lower ratings of postoperative pain-on-average, and pain-at-its-worst than participants receiving sham. In addition, participants who received real TMS rated their mood-at-its-worst as significantly better than participants receiving sham. The effect of a single 20-minute session of TMS on postoperative pain and morphine use appears to be large (Cohen's d = 0.70) and clinically meaningful. Lastly, cross-lag correlational analyses indicate that improvements in mood follow improvements in pain by approximately 12 hours, supporting the notion that postoperative analgesic TMS effects are not driven by antidepressant effects.
  
  
  CONCLUSIONS
  Although more research is needed to verify these observed effects independently, findings from the original postoperative TMS trial were replicated. TMS may have the potential to significantly improve current standards of postoperative care among gastric bypass patients, and further studies may be warranted on other surgical populations. Future investigations should use methodology that permits more definitive conclusions about causal effects of TMS on postoperative pain (for example, double-blinding, sham stimulation that is matched with real TMS with respect to scalp discomfort).
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA. borckard@musc.edu
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Borckardt
authors.forename: Scott T
authors.initials: ST
authors.lastname: Reeves
authors.forename: Mitchel
authors.initials: M
authors.lastname: Weinstein
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Smith
authors.forename: Neal
authors.initials: N
authors.lastname: Shelley
authors.forename: F Andrew
authors.initials: FA
authors.lastname: Kozel
authors.forename: Ziad
authors.initials: Z
authors.lastname: Nahas
authors.forename: Karl T
authors.initials: KT
authors.lastname: Byrne
authors.forename: Katherine
authors.initials: K
authors.lastname: Morgan
authors.forename: Mark S
authors.initials: MS
authors.lastname: George
mesh_terms: D000328:Adult; D000698:Analgesia / Q000379:methods*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D015390:Gastric Bypass / Q000009:adverse effects; D006801:Humans; D009020:Morphine / Q000627:therapeutic use; D010147:Pain Measurement; D010149:Postoperative Pain / Q000209:etiology / Q000628:therapy*; D017397:Prefrontal Cortex / Q000502:physiology*; D011569:Psychiatric Status Rating Scales; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine