Bie, H., Ren, L., & Li, X. A control study of a hypnotic drug plus cranial electrotherapy stimulation in the treatment of insomnia. Journal Clinical Psychosomatic Disorders. 2016; Vol 22, No. 3:17-20.

Funding Source, Location of Study or Author’s Affiliation
Tianjin Occupational Diseases Precaution and Therapeutic Hospital, Tianjin, China

Device
Alpha-Stim^®

Key Variables
Insomnia

Objective
To explore the efficacy of a hypnotic drug plus cranial electrotherapy stimulation (CES) in the treatment of insomnia.

Design
Using a random number table, 152 insomnia patients were assigned to three groups: CES group (n=50), drug (n=51), and combination (n=51). The CES group was treated with CES, the drug group with zopiclone, and the combination group with CES plus zopiclone; for 4 weeks. The degree of disordered sleep was assessed using the Athens Insomnia Scale (AIS) before and after treatment.

Primary Outcome Measure
Insomnia

• Disordered sleep was assessed using the Athens Insomnia Scale (AIS) before treatment, at the end of the 2^nd, and 4^th
• The AIS is an internationally recognized self-report sleep quality assessment scale. Self-reported perceptions, feelings, and opinions about individual changes to sleep quality are used as the assessment of the treatment’s efficacy.
• The AIS scale is a total of 8 questions, scored on 4 levels, reflective of the level of sleep quality.
• The total score for all items in the AIS scale is classified as (i) <4 “No sleep disorder”; (ii) ≥4 as “Probable insomnia”, (iii) >6 “Insomnia”. The higher the AIS total score is, the worse the sleep quality is

Secondary Outcome Measure
None reported.

Key Inclusion Criteria

• Meet diagnostic criteria for non-organic insomnia as per the Diagnostic and Statistical Manual of Mental Disorders in the US Edition 5 (DSM-5).
• Agreement to not use any other drugs that act on the central nervous system during the study or use any measure which has a hypnotic effect or may cause disordered sleep. 

Key Exclusion Criteria

• Organic brain disease.
• Serious physical disease.
• Substance abuse or dependence.
• History of psychiatric disorder.
• Pregnant or breastfeeding.

Protocol Summary
The CES only group received only CES treatment as described below. The medication only group was prescribed a once nightly dose of 7.5mg of zopiclone. The combination group received the same CES treatment protocol as the CES only group and the same medication regiment as the MED only group.

Device Application Protocol
The Alpha-Stim device was used to administer CES treatment. Patients were instructed to remain seated during CES treatment, check that the CES device and leads were connected, apply conducting solution to both electrode pads, and then clamp them bilaterally to each earlobe, and turn the device on. The current intensity was self-adjusted ranged between 10-500 μA, and the frequency was 1.5 Hz. Patients were then instructed to adjust the intensity from the lowest setting until they felt a mild tingling but comfortable sensation. The mild tingling or mild dizziness of patients is considered a normal phenomenon during treatment. The treatment time was once a day, for 60 minutes each time.

Statistical Analysis Plan
Change in insomnia symptoms from baseline to posttreatment in the AIS scale was used as a measure of treatment efficacy. All data were processed by SPSS15.0 statistical package, the measurement data tested by t-test, and the enumeration data tested by χ².

Results

Subjects
A total of 152 patients were enrolled in the study, (i) fifty (n=50) in the CES group, (ii) fifty-one (n=51) in the MED group, and (iii) fifty-one (n=51) in the MED+CES group.

There were 23 males and 27 females in CES group, aged 27-66 years, mean age of 51.5±3.0 years, and a disease course of 3-40 months, and a mean of 12.3±2.5 months on average.

The MED group included 24 males and 27 females, aged 28-69 years, mean age of 47.5±6.2 years and disease course of 3-37 months, 13.1±2.7 months on average.

There were 24 males and 27 females in the MED+CES group aged 29-67 years, and 48.5±5.2 years on average, with disease course of between 3-36 months, on average 13.3±2.3 months.

There were no significant differences in gender, age, and course of disease of the three groups (p>.05).

Data Analysis
The effective rate of the CES group was 76.0%, MED group was 76.5%, and MED+CES group was 84.3% at the end of the 4^th week. The results confirmed an effective rate of the combination group (MED+CES) as being higher than that of the CES only group (CES), and the drug group (MED). The effective rate between the three groups is different but not significantly so (χ²=0.23, p>.05).

The AIS total scores of the three groups after treatment were significantly lower than pretreatment (p<.01). The AIS total scores of the MED+CES group at the end of the 2^nd and 4^th week were significantly lower than those of the CES group and MED group (p<.01 and p<.05 respectively).

The AIS total score of the MED group at the end of the 2^nd week was significantly lower compared with that of the CES group (p<.01) and was not significantly (p>.05) different from the CES group at the end of the 4^th week.

Comparison of AIS scores of three groups before and after treatment 

Mean changes in AIS total scores for MED, CES, and MED+CES groups

Conclusion
The study shows that AIS total scores of the three groups after treatment were significantly reduced compared with pretreatment (p<.01), but AIS total scores for the drug group and combination group at the end of the 2^nd week were significantly lower than those of the CES only group. This finding is consistent with clinical use of Alpha-Stim to treat insomnia, as it can take four weeks for patients to achieve the full benefit in treating insomnia with CES. The results from this study suggest that the drug (MED) and the drug plus CES (MED+CES) treatment take effect more quickly than CES alone (CES). At the end of the 4^th week, the AIS total score of the combination group (MED+CES) was significantly lower than the CES only (CES) group and the drug only (MED) group. These results suggest CES and Zoplicone have equivalent efficacy in the treatment of insomnia, and have a cumulative effect over time, but the combination of the two has a synergistic or augmentative quality and can reinforce treatment effectiveness and improve sleep quality. In conclusion, CES and hypnotic medication have equivalent efficacy in the treatment of insomnia, and CES provides an effective means for a non-drug treatment of insomnia, but the combination of the two has a superior effect and can reinforce treatment effectiveness and improve sleep quality.

Limitations
This is a well-designed randomized controlled trial, but no blinding occurred. Therefore, according to the Cochrane Risk of Bias guidelines, it is possible for bias to be unintentionally introduced into the results of the study. The authors indicate a disadvantage of this study is that the AIS is a self-report sleep quality scale, that measures subjective feelings about sleep. The study did not have an objective indicator or assessment of sleep quality. Another disadvantage is the reported frequency (1.5 Hz) used for CES in this study. The patented Alpha-Stim waveform is designed for a frequency of 0.5 Hz, therefore higher frequencies are not as effective for CES treatment.

Study Quality: FAIR