Clinical Efficacy of Assisted Cranial Electrotherapy Stimulation Treatment on Depression

 

Wei Y., Yang Z., Pan H., Zhao S-J., Fang J-Z. Clinical Efficacy of Assisted Cranial Electrotherapy Stimulation Treatment on Depression. Neural Injury and Functional Reconstruction. July 2014, 9(4):317.

Funding Source, Location of Study, or Author’s Affiliation
Department of Psychiatry, The Third People’s Hospital of Changshu City, Jiangsu 215500, China

Device
Alpha-Stim®

Key Variables
Depression and anxiety.

Objective
To observe the curative effect and safety of antidepressants combined with cranial electrotherapy stimulation (CES) in treatment for depression patients

Design
A group of patients diagnosed with depression and anxiety were randomly allocated into two groups. The control group received antidepressant medication, and the experimental group CES. The treatment cycle for both groups was 6 weeks. Pre- and post-treatment depression scores were measured using the Hamilton Depression Rating Scale (HAM-D) and anxiety using the Hamilton Anxiety Rating Scale (HAM-A). The level of cognitive impairment was assessed using the Wisconsin Card Sorting Test (WCST). With the safety of the treatment modalities assed using the Treatment Emergent Symptom Scale (TESS).

Primary Outcome Measure
Pre and post scores for:

  • Depression measured by Hamilton Depression Rating Scale (HAM-D)
  • Anxiety assessed by the Hamilton Anxiety Rating Scale (HAM-A)

Secondary Outcome Measure

  • Cognition as measured by the Wisconsin Card Sorting Test (WCST)
  • Safety as assessed by Treatment Emergent Symptom Scale (TESS)

Key Inclusion Criteria

  • Diagnosis of depression following the Classification and Diagnostic Criteria of Mental Disorders in China Edition 3 (CCMD-3)
  • HAM-D ≥17
  • Male or female aged 16-68 years old

Key Exclusion Criteria

  • Prior diagnosis of a neurodegenerative disease
  • History of or current substance use or dependence
  • Pregnant, lactating, or planning to become pregnant
  • Diagnosis of epilepsy
  • Implanted medical devices, including pacemakers, insulin pumps

Protocol Summary

  • A total of 80 patients were randomly allocated into two groups of 40. Both groups received Treatment as Usual (TAU) consisting of antidepressant medication, with the experimental group receiving CES using Alpha-Stim in addition to medication (TAU+CES).
  • The drug classes for the antidepressant medication included Noradrenergic and Specific Serotonergic Antidepressants (NaSSA), Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), Selective Serotonin Reuptake Inhibitor (SSRIs), Serotonin Antagonist and Reuptake Inhibitors (SARIs), and Tricyclic Antidepressants (TCAs).
Drug Class Condition & Frequency
TAU+CES TAU
Noradrenergic and Specific Serotonergic Antidepressants (NaSSA) 14 14
Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) 12 13
Selective Serotonin Reuptake Inhibitor (SSRIs) 9 7
Serotonin Antagonist and Reuptake Inhibitors (SARIs) 3 3
Tricyclic Antidepressants (TCAs) 2 3
Total 40 40

The number of patients in each drug class.

  • During the CES treatment cycles, combination with other medications or treatments was not permitted (i.e., antipsychotics, antidepressants, mood stabilizers, electric convulsive therapy, or systematic psychotherapy).
  • CES therapy was administered using Alpha-Stim as per the manufacturer’s instructions. Subjects received four courses of treatment, each treatment cycle lasting 20 minutes, over five days, with a two-day rest period between treatment cycles, resulting in 20 days of treatment over six weeks.
  • The symptom severity and adverse drug reactions were evaluated respectively at the time of admission and the end of 1, 2, 4, and 6 weeks of treatment, and patients’ cognitive functions were evaluated at the time of admission and the end of the 6th week.
  • Treatment response was assessed by two attending psychiatrists who had been rigorously trained, respectively evaluated the individuals in the two groups and tested their consistency on their scale evaluations (Kappa=0.86).

Device Application Protocol
Patients were instructed to (1) clean their earlobes with a wet cotton pad, (2) apply the conductive solution, and (3) gently clamp the electrodes around the base of their earlobes. Patients were advised to relax and lay down in a location where they would not be disturbed. Instructions to set the Alpha-Stim CES device to a frequency of 0.5 Hz and intensity between 10-500 μA were given to patients. Each patient had the ability to self-calibrated the minimum threshold of intensity by gradually increasing it until they experienced a mild tingling sensation. The course of treatment was 20-minutes over a five-day period.  Each course was started two days after completion of the former one, and each patient received four courses of treatment, 20 treatments in total.

Statistical Analysis Plan

  • The reduction of HAM-D scores was used as the evaluation indicator of efficacy (i.e., HAM-D score ≤7 indicating clinical recovery, and HAM-D reduction ≥50% indicating effectiveness).
  • Significance testing using t-tests, chi-square, and repeated measures Analysis of Variance (ANOVA) at a statistically significant level of p<0.05.
  • SPSS 17.0 statistical software was used to analyze the data.

Results

Subjects

  • The TAU+CES condition included 40 patients, 15 males, and 25 females, with a mean (SD) age of 36.36±13.53 years, and a depression diagnosis with a mean (SD) of 18.74±16.25 weeks; with six patients having a family history of depression. The mean (SD) total HAM-D score at baseline was 25.32±5.24.
  • The TAU group included 12 males and 28 females, a total of 40 subjects with a mean (SD) age of 34.72±12.48 years, and a diagnosis of depression of with a mean (SD) of 71±15.52 weeks; of which seven subjects reported a family history of depression. The mean (SD) total HAM-D score at baseline was 25.89±4.67.
  • The dose of each antidepressant drug was adjusted to the therapeutic dose within 1-2 weeks according to individual tolerance. The difference in type, composition and mean dose of antidepressant drugs between the two groups was not significant (p>0.05).
  • No significant differences between groups in cognitive impairment as measured by WCST scores were reported at baseline.
  • No significant changes in hemogram, ECG, liver, and kidney functions were found between the two groups.
  • A total of five patients across the two groups did not complete or were withdrawn from the study. The difference in withdrawal rate between the two groups was not statistically significant (x2=0.213, p>0.05).

Data Analysis
After the treatment the HAM-D and HAM-A scores in the two groups were significantly lower than before treatment (p<0.01). In the sixth week, the assisted efficiency and curative rates between the two groups showed no significant difference (p>0.05). In the 4th week, the efficiency in the TAU+CES group was significantly higher than in TAU group (p< 0.05).

Mean HAM-D Score Baseline Through Week 6 of Treatment

Mean HAM-A Score at Baseline Through Week 6 of Treatment.

Efficacy: The efficacy of treatment was assessed at Weeks 2, 4, and 6, and shown in the table below.  The efficacy and curability rate of the TAU+CES condition was significantly higher (p<0.05) at the 4th week of treatment than the TAU condition. No significant difference in efficacy or curability between the two con