title: Efficacy and safety of a form of cranial electrical stimulation (CES) as an add-on intervention for treatment-resistant major depressive disorder: A three week double blind pilot study.
abstract: We examined efficacy and safety of one specific cranial electrical stimulator (CES) device at a fixed setting in subjects with treatment-resistant major depressive disorder (MDD). Thirty subjects (57% female, mean age 48.1 ± 12.3 years) with MDD and inadequate response to standard antidepressants were randomized to 3 weeks of treatment with CES (15/500/15,000 Hz, symmetrical rectangular biphasic current of 1-4 mAmp, 40 V) or sham CES (device off) for 20 min, 5 days per week. The primary outcome measure was improvement in the 17-item Hamilton Depression Rating Scale (HAM-D-17). Adverse effects (AEs) were assessed using the Patient Related Inventory of Side Effects (PRISE). Completion rates were 88% for CES, 100% for sham. Both treatment groups demonstrated improvement of about 3-5 points in HAM-D-17 scores (p < 0.05 for both), and no significant differences were observed between groups. Remission rates were 12% for CES, and 15% for sham, a nonsignificant difference. CES was deemed safe, with good tolerability; poor concentration and malaise were the only distressing AEs that differed significantly between CES and sham (p = 0.019 and p = 0.043, respectively). Limitations include a small sample and lack of an active comparator therapy. Although both treatment groups improved significantly, this CES at the setting chosen did not separate from sham in this sample. Thus we cannot rule out that the benefit from this setting used in this particular form of CES was due to placebo effects. Since this form of CES has other settings, future studies should test these settings and compare it against other CES devices. Clinicaltrials.gov ID: NCT01325532.
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Electronic address: dmischoulon@partners.org.
authors.forename: David
authors.initials: D
authors.lastname: Mischoulon
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Marasha F
authors.initials: MF
authors.lastname: De Jong
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Ottavio V
authors.initials: OV
authors.lastname: Vitolo
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cusin
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Dording
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Albert S
authors.initials: AS
authors.lastname: Yeung
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kelley
authors.initials: K
authors.lastname: Durham
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Susannah R
authors.initials: SR
authors.lastname: Parkin
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Darin D
authors.initials: DD
authors.lastname: Dougherty
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D003865:Major Depressive Disorder / Q000628:therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy*; D004311:Double-Blind Method; D004599:Electric Stimulation Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents
keywords: CES; Cranial electrical stimulation; Major depression; Treatment resistant depression