Acupuncture combined with cranial electrotherapy stimulation on generalized anxiety disorder: A randomized controlled trial

 

Liu, E., Zhang, W., Wang, J., Zhao, F., & Bai, Y. Acupuncture combined with cranial electrotherapy stimulation on generalized anxiety disorder: A randomized controlled trial. Chinese Acupuncture & Moxibustion. 2020; 40(11).

Funding Source, Location of Study or Author’s Affiliation
Department of TCM, First Hospital of Hebei Medical University, Shijiazhuang, China

Device
Alpha-Stim® SCS

Key Variables
Anxiety and Quality of Life.

Objective
To observe the therapeutic effect of acupuncture combined with cranial electrotherapy stimulation (CES) on generalized anxiety disorder (GAD).

Design
A randomized controlled study comparing the effectiveness of four (K=4) different treatment groups (1) medication only (MED), (2) acupuncture only (ACU), (3) cranial electrotherapy stimulation only (CES), and (4) acupuncture plus CES (ACU + CES) for the treatment of generalized anxiety disorder (GAD). The medication only (MED) group was considered the control group as it received treatment-as-usual (TAU), and the acupuncture only (ACU) and CES only (CES) and acupuncture plus CES (ACU+CES) are the experimental groups.

Baseline and post-treatment anxiety scores were measured using the Hamilton Anxiety Rating (HAM-A) scale. Similarly, baseline and end of treatment quality of life were assessed using the World Health Organization Quality of Life Questionnaire-Brief Version (WHOQOL-BREF). Adverse events were measured using the Treatment Emergent Symptom Scale (TESS). Patients were assessed at the end of the study and relapse rates reassessed 12 months after the end of treatment.

Primary Outcome Measure

  • Anxiety
    • Assessed using the Hamilton Anxiety Rating Scale (HAM-A).
    • The HAM-A includes a severity scale for each item from 0 “Not present” to 4 “Severe”
    • Scores range from 0–56 with <17 indicating “Mild severity”; 18–24 “Mild to moderate severity”, and 25–30 “Moderate to severe”.
  • Quality of Life
  • Measured by the World Health Organization’s Quality of Life Questionnaire Brief Version (WHOQOL-BREF)
  • The WHOQOL-BREF is a 26-item instrument consisting of four domains: physical health (7 items), psychological health (6 items), social relationships (3 items), and environmental health (8 items), and other general health items.
  • Each item in the WHOQOL-BREF is scored from 1 to 5 on a response scale.

Secondary Outcome Measure

  • Side Effects
  • Measured by the Treatment Emergent Symptom Scale (TESS).
  • The TESS scale is used to assess adverse events that first occurred or worsened in severity after initiation of treatment or therapy.
  • The scale includes measures of behavioral toxicity, laboratory abnormalities, cardiovascular, autonomic, and nervous system reactions, body weight, headache, and appetite changes.
  • Scores range from 0 to 4, with a higher score indicative of more serious adverse reactions.

Key Inclusion Criteria

  • Met criteria for Generalized Anxiety Disorder (GAD) according to the Chinese Classification of Mental Disorder, 3rd edition (CCMD-3). The clinical manifestations of GAD include restlessness, insomnia, a sense of dread, feeling constantly “on edge”, dizziness, irritability, difficulty concentrating, and muscular tension or pain.
  • Diagnosis of GAD ≥6 months
  • Hamilton Anxiety Rating (HAM-A) scale ≥14
  • Age <80 years
  • Provide informed consent
  • Be willing to be randomized into one of the treatment groups
  • Follow the study protocol

Key Exclusion Criteria

  • Chronic medical conditions such as severe heart, brain, liver, kidney, hematopoietic system, etc.
  • Not a good candidate or unfit for CES or acupuncture treatment.
  • Use of anxiolytic medication in the last two weeks or discontinued medication within the last two weeks.
  • Other psychiatric disorders.

Protocol Summary
Patients in all four groups (K=4) received treatment for sixty (60) days irrespective of group assignment.

  • Medication only (MED): in the medication (MED) only TAU group patients were treated with oral tandospirone citrate (brand name Sediel) an anxiolytic and antidepressant drug used in China and Japan. The dosage was 10mg after breakfast, lunch, and dinner.
  • CES only (CES): the CES only (CES) group received treatment using the Alpha-Stim® SCS device daily for 60 minutes each time.
  • Acupuncture only (ACU): the acupuncture only (ACU) group received traditional acupuncture applied daily for 30 minutes to (1) Baihui (GV 20), (2) Sishencong (EX-HN 1), (3) Yintang (GV 29),(4) Shenting (GV 24), etc.
  • Acupuncture plus CES (ACU+CES): the acupuncture plus CES (ACU+CES) group received CES treatment before acupuncture. The treatment protocol for the acupuncture and CES were the same as the acupuncture only (ACU) and CES only (CES) group.

Device Application Protocol
CES was administered using the Alpha-Stim® SCS, and patients were instructed to lay supine or sit comfortably, saturate the electrode pad with conducting liquid, then clamp the electrode at the base of both earlobes. Once the device was attached patients were instructed to turn the power switch on and adjust the intensity from level 0-5 until a slight feeling of dizziness or a sensation of tingling on the earlobes occurred. Treatment was daily, for 60 minutes each time, for 60 continuous days of the treatment trial.

Statistical Analysis Plan
Changes in HAM-A and WHOQOL were observed, the clinical effect was evaluated, and the anxiety relapse rate was measured in all four groups at follow-up one year after treatment ended. The relapse rate was set at a HAM-A score ≥14.

The therapeutic effect was evaluated by comparing the change in HAM-A scores. HAMA score indicator = [(HAM-A score before treatment – HAM-A score after treatment)/HAM-A score before treatment] ×100%. The results were interpreted as HAM-A score (1) ≥75% “Cured”, (2) 50%≤ HAM-A score indicator <75% “Excellent”, (3) 25%≤ HAM-A score indicator <50% “Effective”, (4) <25% HAM-A score indicator “Ineffective”.

SPSS 18.0 software was used for statistical analysis, and the measurement data were described by mean ± standard deviation (SD). The comparison among groups is used with single-factor analysis of variance (ANOVA), and the comparison between two groups is checked by Least Significant Difference (LSD); the enumeration data is checked by χ2. A significance level of p<.05 is used to determine a statistically significant difference.

Results

Subjects
A total of 200 patients with GAD were randomly allocated into four groups (K=4) using a random number table, with 50 cases per group (n=50). Comparison of subjects’ general characteristics at baseline across all groups, including gender, age, and course of the disease were not statistically significant (p>.05). The groups can be considered comparable.

The MED only (MED) group included 22 males and 28 females, aged 27-70 years, representing a mean age 38±3 years, and a course of disease between 6-40 months, equating to a mean course of 13.6±2.6 months.

In the CES only (CES) group  22 males and 28 females aged 25-69 years were enrolled, with a mean age of 37±3 years, and a course of disease between 7-39 months, reflecting a mean of 13.0±3.1 months since disease onset.

The acupuncture only (ACU) group enrolled 20 males and 30 females, aged 25-71 years, reflecting a mean age of 38±3 years, and a course of disease ranging from 6-41 months, with a mean onset of 14.0±2.4 months.

The acupuncture plus CES group (ACU+CES) enrolled 21 males and 29 females aged from 27-72 years old and having a mean age of 38±2 years, and a disease course of 7-42 months, and a mean of 13.5±2.7 months since onset.

Data Analysis
Across all four groups, patients reported benefitting from the treatment they received. The level of anxiety was significantly reduced as evidenced by the lower HAM-A scores (p<.05). Furthermore, quality of life as measured by the WHOQOL- BREF significantly improved following treatment as indicated by the higher scores post-treatment (p<.05).

Anxiety:

No statistically significant difference in the level of anxiety between the four groups was reported before treatment (p>.05). Following treatment, the HAM-A score of all four groups decreased significantly (p<.05). The acupuncture plus CES (ACU+CES) group rep