Effects of Cranial Electrotherapy Stimulation on the Levels of HPA, BDNF and Clinical Symptoms in Patients with Mild Depression

Kong, S., Gao, C., & Yang, Z. Journal of International Psychiatry. 2021; 48(1).

Objective

To investigate the effects of cranial electrotherapy stimulation (CES) on the hypothalamic-pituitary-adrenal (HPA) axis, levels of brain-derived neurotrophic factor (BDNF), and clinical symptoms in patients with mild depression.

Design

A randomized sham-controlled study of eighty-six patients with mild depression divided into two groups. Blood samples were collected before and after 8 weeks of treatment to measure cortisol (COR), adrenocorticotropic hormone (ACTH), and brain-derived neurotrophic factor (BDNF). Accompanying depression, anxiety, and sleep measures were taken pre and post-treatment. Depression was measured using the Hamilton Depression (HAM-D) and anxiety using the Hamilton Anxiety (HAM-A) rating scales. Insomnia was assessed using the Insomnia Severity Index (ISI). Patients received either active or sham CES for 20 minutes per session, 3 times per week, over 8 weeks.

Primary Outcome Measure

Blood serum levels of:

• COR
• ACTH
• BDNF

Secondary Outcome Measure

• Depression, as evaluated using the 17 items HAM-D rating scale.
• Anxiety, as evaluated using the 14 item HAM-A rating scale.
• Sleep as measured by the ISI and indicative of the quality of sleep in the previous two weeks.

Key Inclusion Criteria

• Depression – meet diagnostic criteria as per the International Classification of Diseases (ICD-10) for mild depression or a HAM-D score of 17-24.
• Anxiety – a HAM-A score of 7-20.
• Age – between 18-60 years.
• Body Mass Index (BMI) lower than 30kg/m2.
• No antidepressant medication, electric convulsive treatment (ECT), or other psychiatric treatments in the past four weeks.

Protocol Summary

A total of 86 patients with mild depression were enrolled in the study. Subjects were randomly assigned to the study group and control group using a random number table. All subjects were diagnosed with mild depression and underwent a weekly psychological evaluation and were withdrawn from the study if their symptoms worsened or they developed suicidal ideation or intent.

Device Application Protocol

Patients in the active and sham conditions received CES treatment using the Alpha-Stim® SCS device. The treatment protocol was 3 times every week, for 20 minutes, over 8 weeks. The clamp electrodes in the CES device were attached bilaterally to the earlobes and the electrodes connected to the device. The intensity was set to 10-500 μA and the frequency to 0.5Hz. Patients were able to gradually increase the intensity until they felt a mild tingling sensation. The device used in the sham condition was applied in the same way, but the power of the device was turned off.

Results

After treatment, the HAM-A and ISI scores in the active CES group decreased significantly and were significantly lower than the sham CES group. The change in HAM-D from baseline to post-treatment was significant, however, the difference between the active and sham conditions was not statistically significant.

After treatment, the concentration of COR in the active CES group decreased and was significantly lower than that of the sham condition. The change in ACTH and BDNF levels from baseline to post-treatment was not significant.

Conclusion

The results from the study demonstrated CES treatment resulted in changes to COR plasma concentrations in patients with mild depression but did not cause significant changes to levels of ACTH and BDNF. The authors concluded that CES treatment plays a positive role in improving anxiety and insomnia symptoms in patients with mild depression, but its effect on depression was poor. Stating that the observable changes in hormone levels of patients with mild depression following CES treatment are likely associated with stimulation of the HPA axis, and the reason for the accompanying reduction in symptoms of anxiety and insomnia, but not depression. The authors proposed that stimulation of the HPA axis is likely one of the possible mechanisms of action CES.

Study Quality: FAIR