Abstract
Background
Suicide attempts and completed suicides are common, yet there are no proven acute
medication or device treatments for treating a suicidal crisis. Repeated daily left
prefrontal repetitive transcranial magnetic stimulation (rTMS) for 4–6 weeks is a
new FDA-approved treatment for acute depression. Some open-label rTMS studies have
found rapid reductions in suicidality.
Design
This study tests whether a high dose of rTMS to suicidal inpatients is feasible and
safe, and also whether this higher dosing might rapidly improve suicidal thinking.
This prospective, 2-site, randomized, active sham-controlled (1:1 randomization) design
incorporated 9 sessions of rTMS over 3 days as adjunctive to usual inpatient suicidality
treatment. The setting was two inpatient military hospital wards (one VA, the other
DOD).
Patients
Research staff screened approximately 377 inpatients, yielding 41 adults admitted
for suicidal crisis. Because of the funding source, all patients also had either post-traumatic
stress disorder, mild traumatic brain injury, or both.
TMS methods
Repetitive TMS (rTMS) was delivered to the left prefrontal cortex with a figure-eight
solid core coil at 120% motor threshold, 10 Hertz (Hz), 5 second (s) train duration,
10 s intertrain interval for 30 minutes (6000 pulses) 3 times daily for 3 days (total
9 sessions; 54,000 stimuli). Sham rTMS used a similar coil that contained a metal
insert blocking the magnetic field and utilized electrodes on the scalp, which delivered
a matched somatosensory sensation.
Main outcome measure
Primary outcomes were the daily change in severity of suicidal thinking as measured
by the Beck Scale of Suicidal Ideation (SSI) administered at baseline and then daily,
as well as subjective visual analog scale measures before and after each TMS session.
Mixed model repeated measures (MMRM) analysis was performed on modified intent to
treat (mITT) and completer populations.
Results
This intense schedule of rTMS with suicidal inpatients was feasible and safe. Minimal
side effects occurred, none differing by arm, and the 3-day retention rate was 88%.
No one died of suicide within the 6 month followup. From the mITT analyses, SSI scores
declined rapidly over the 3 days for both groups (sham change −15.3 points, active
change −15.4 points), with a trend for more rapid decline on the first day with active
rTMS (sham change −6.4 points, active −10.7 points, P = 0.12). This decline was more pronounced in the completers subgroup [sham change −5.9
(95% CI: −10.1, −1.7), active −13 points (95% CI: −18.7, −7.4); P = 0.054]. Subjective ratings of ‘being bothered by thoughts of suicide’ declined
non-significantly more with active rTMS than with sham at the end of 9 sessions of
treatment in the mITT analysis [sham change −31.9 (95% CI: −41.7, −22.0), active change −42.5
(95% CI: −53.8, −31.2); P = 0.17]. There was a significant decrease in the completers sample [sham change −24.9
(95% CI: −34.4, −15.3), active change −43.8 (95% CI: −57.2, −30.3); P = 0.028].
Conclusions
Delivering high doses of left prefrontal rTMS over three days (54,000 stimuli) to
suicidal inpatients is possible and safe, with few side effects and no worsening of
suicidal thinking. The suggestions of a rapid anti-suicide effect (day 1 SSI data,
Visual Analogue Scale data over the 3 days) need to be tested for replication in a
larger sample.
Trial registration
ClinicalTrials.gov Identifier: NCT01212848, TMS for suicidal ideation.
Keywords
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Article info
Publication history
Published online: March 21, 2014
Accepted:
March 11,
2014
Received in revised form:
March 7,
2014
Received:
December 9,
2013
Footnotes
Funded by U.S. Army Medical Research and Materiel Command (USAMRMC).
Funding mechanism: Contract #W81XWH-08-2-0159, DOD INTRuST.
Conflicts of interest: Relationship with the vendor: Although the equipment was loaned for this trial from one vendor (Neuronetics), significant firewalls existed between the vendor and the trial, similar to the NIH OPT-TMS trial. None of the investigators has any financial conflict of interest with the vendor, other than other TMS research studies, nor have they for the past 5 years. Second, the equipment was loaned for the trial but the study design, conduct, data, data analysis and manuscripts to emerge are independent of the vendor and did not involve the vendor. The vendor was notified of safety issues and device malfunctions as they must notify the FDA about this regarding their device.
Dr. George has no equity stake in any TMS device manufacturer and does not accept speaker or consultant fees from TMS device manufacturers. He has had research studies within the past three years with Neuronetics, Brainsway, Cervel, Neosync, St. Judes, Medtronic and MECTA.
Identification
Copyright
© 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
