Treatment of Sleep Disorder with Cranial Electrotherapy Stimulation Combined with Psychological Counseling in Postmenopausal Women: A Randomized Study

 

Kong, J., Wu, J., Jiang, X., et al. Treatment of Sleep Disorder with Cranial Electrotherapy Stimulation Combined with Psychological Counseling in Postmenopausal Women: A Randomized Study. Chinese Journal of Medicinal Guide. 2014; 921, 16(6):(Serial No.128).

Funding Source, Location of Study, or Author’s Affiliation
Women Health Care, Nanjing Maternity and Child Health Care Hospital, Nanjing, China

Device
Alpha-Stim®

Key Variables
Menopausal symptoms, sleep, depression, and anxiety.

Objective
To compare the effects of Cranial Electrotherapy Stimulation (CES) combined with psychological counseling for the treatment of disordered sleep in post-menopausal women.

Design
Investigate the occurrence of insomnia and its frequently secondary impact on depression, anxiety, and quality of life in peri- and post-menopausal women. Assess the efficacy of CES, a non-pharmacological FDA cleared treatment for insomnia in conjunction with psychological counseling and compare it to psychological counselling alone. Measure changes in symptom profile at baseline, 4, and 8 weeks after treatment.

Primary Outcome Measure

  • Menopausal symptoms as measured by the Kupperman Index (KI) based on the grade of 0-3. The KI items include
    • Vasomotor symptoms (hectic fever and sweating)
    • Sensory disturbance
    • Insomnia
    • Depression
    • Dizziness
    • Fatigue
    • Joint and muscle pain
    • Headache
    • Palpitation
    • Skin formication
    • Hyposexuality
    • Urinary tract infection
  • Sleep as measured by the Pittsburg Sleep Quality Index (PSQI) based on the grading score of 0-3 on the 18 scoring items divided into the 7 components of sleep:
    • Quality
    • Latency
    • Duration
    • Efficiency
    • Disturbance
    • Daytime dysfunction
    • Medication use

Secondary Outcome Measure

  • Anxiety indicated by the Self-Rating Anxiety Scale (SAS) based on the grade scoring of 1-4
  • Depression assessed by the Self-Rating Depression Scale (SDS) based on the scoring grade of 1-4

Key Inclusion Criteria

  • Pittsburgh Sleep Quality Index (PSQI) score ≥7
  • Women aged ≥40 and ≤60 years old amenorrhea for ≥3 and ≤12 months
  • Perimenopausal symptoms as indicated by a score of ≥15 in the modified KI
  • Aged ≥40 years old with inconsistent menstrual cycles not attributed to pregnancy
  • Follicle Stimulating Hormone (FSH) levels ≥10U/L
  • Women who have undergone artificial menopause or ovarian ablation ≥ 6 weeks with FSH ≥10U/L
  • Intact uterus and bilateral ovaries

Key Exclusion Criteria

  • Non-perimenopausal women
  • Sex hormone treatment in preceding three months
  • Diagnosis of
    • Hyperthyroidism
    • Coronary atherosclerotic heart disease
    • Hypertension or pheochromocytoma
    • Neurasthenia
    • Psychosis
    • Other diseases closely associated with primary symptoms
  • Taking medication for insomnia, anxiety, or depression
  • Men

Protocol Summary
A randomized Intent-to-Treat (ITT) study of women aged 35-40 years presenting with disordered sleep and meeting full eligibility criteria were enrolled in the study. A total of 139 women were randomly allocated into two groups. Group A received psychological counseling and CES (CES+PSY). Group B received weekly psychological counseling (PSY). Peri- and post-menopausal symptoms were assessed following the Technical Guidelines for Clinical Research on Treatment of Menopausal Syndrome with Traditional Chinese Medicine (TCM) and Natural Medicines issued by the China Food and Drug Administration. FSH levels were taken on the 3rd day of menstruation for peri-menopausal women. Women in the PSY + CES condition received treatment using the Alpha-Stim daily for 60 minutes over eight weeks and psychological counseling once a week. Patients receive supervision for the first three treatment sessions and then self-administered CES at home for the remainder of the study. The comparator group received psychological counseling once a week for eight weeks.

Device Application Protocol
Alpha-Stim was used to administer CES to Group A (CES+PSY). Patients were instructed to turn on the power, coat the bilateral earclips with conductive fluid and attach them to each earlobe. During self-administration, patients were instructed to gradually increase the current intensity from 10-500 μA, and to calibrate the maximum dosage at a level that was comfortable for them or when they felt a tingling sensation. The duration of each treatment cycle was 60 minutes and occurred daily over eight weeks.

Statistical Analysis Plan
Using prevalence rates for insomnia among peri- and post-menopausal women, a power calculation estimated a sample size of 60 cases, with the margin for a withdrawal rate of 20%, the total cases were determined as 72. The ratio of the experimental group to the control group was 1:1, and the random coding table followed the order in which the cases were selected. Software was used to obtain random numbers and to generate random grouping. Data analysis was conducted using SPSS 17.0 and Excel 2010. Statistical analysis included t-test, chi-square test, and analysis of variance (ANOVA). Higher scores are indicative of greater impairment (e.g., high KI indicative of multiple menopausal symptoms or high PSQI score suggestive of poorer sleep quality) and taken at baseline, followed by 4- and 8-weeks post-treatment.

Results

Subjects
A total of 139 peri- and post-menopausal women aged 35-40 years were recruited to the study as they attended the Nanjing Maternity and Child Health Care Hospital, in China. The rate of subject attrition was 12.2% (N=17), with eight patients lost to follow up or withdrawn from the study before or at baseline, resulting in 131 patients considered in the ITT analysis. A further nine patients withdrew from during treatment, resulting in 122 patients completing the 8-week study, with 63 cases in Group A and 59 cases in Group B. The mean (SD) age of Group A was 47±4 years and 46±4 years in Group B. The difference in age distribution between conditions was not statistically significant (p=0.52). The difference in marital status, education level, etc. was also not statistically significant (p=0.38, p=0.20).

Data Analysis
Menopausal Symptoms: The KI scores at baseline between the two groups were not significantly different (p=0.67) with a mean (SD) of 22.5±7.1 for the CES+PSY group and 23.3±6.2 for the PSY group. The reduction in KI scores in the CES+PSY group after four weeks was more than 7, suggesting an improvement in peri-menopausal symptoms, and after 8 weeks, the reduction was 12.4, suggesting a greater reduction in symptoms with prolonged CES treatment. In comparison, for the PSY group, at 4 weeks the reduction in KI scores was 4 and 5.6 at 8 weeks (p=0.00). Further details are shown in the following table.

Comparison of mean and standard deviation of peri-menopausal symptoms and sleep quality before and after treatment in both groups.

Anxiety & Depression Symptoms: Patients in both groups showed symptoms of moderate to severe depression and anxiety at baseline, but no significant difference between the groups was reported (p>0.05). After eight weeks of psychological counseling and the addition of CES in Group A, depression and anxiety symptoms of both groups were significantly lower, with a symptom reduction rate of over 50%. The mean improvement rate of depression and anxiety symptoms in CES+PSY was 7%-10% higher than that of PSY the group, a statistical