Introduction

Anxiety, depression, and insomnia are considered to be among the alterations that generate disturbance in people who suffer them¹,². It is estimated that these changes may be present even in one-third of the world's population³-⁵, and in Mexico, they can reach similar numbers⁶-⁸. These disorders are associated with the pathophysiology of the brain. Insomnia and anxiety include an increase of emotional, cognitive, somatic, and cortical excitability⁹,¹⁰ while depression is associated with the decrease of cortical activity in prefrontal areas and the anterior cingulate gyrus¹¹. Many interventions focus on drug treatments¹²-¹⁴, but they often have certain limitations, such as cost, side effects, and a decrease of its efficiency and the quality of patient's lifestyles¹⁵-¹⁷. The non-pharmacological approaches for the treatment of these disorders are diverse and its effectiveness is still in research¹⁸,¹⁹. Non-invasive brain stimulation techniques are used as an alternative to pharmacological treatment and they have shown a notable upturn in recent decades²⁰.

Cranial electrical stimulation (CES) is a non-invasive neurophysiological technique that works through low-intensity pulses of electric current of ≤ 4 milliamperes (mA) in frequencies from 0.5 to 15,000 Hz, through two electrodes placed on the scalp²¹. The CES is safe²² and it has been employed on different disorders such as major depression, anxiety, post-traumatic stress disorder, and insomnia²³. Brain stimulation with alternating current (AC) such as CES has important approaches in the treatment of anxiety, depression, and insomnia²⁴, however, it requires greater attention on its mechanism of action, especially in clinical research.

The mechanism of the CES on clinical symptoms has been explained at different levels on the nervous system. On the one hand, it is believed that the CES affects subcortical structures such as the reticular activating system, the thalamus, hypothalamus, and limbic system¹⁶,²¹. Brain imaging studies suggest a cortical deactivation in the prefrontal and parietal midline of the brain after 20 min of CES²⁵. In addition, it is proposed that the effects of CES include both cortical and subcortical areas producing changes similar to the use of anti-anxiety medications²⁶. At the electrophysiological level, it is observed an increase in alpha activity and a decrease in delta and beta activity²⁷. At a biochemical level, it is suggested an increase in endorphins, adrenocorticotropic hormone, serotonin, melatonin, norepinephrine, cholinesterase, and reduction of cortisol²¹.

Given that the electrodes are placed over the scalp, this technique is considered a form of peripheral nerve stimulation. Although the positive effects of the CES have been observed in different levels of the nervous system, its efficacy on clinical symptoms is not yet conclusive. However, the use of the CES in the clinical practice has increased steadily in recent decades, so it is required the application of empirical studies which can be distinguished from the placebo effect.

Method

Participants

Twenty-six cases that covered the insomnia symptoms based on the International Classification of Sleep Disorders (ICSD) were considered initially². The inclusion criteria were to be over 18 years old and the exclusion criteria were having antecedents of epilepsy, receive treatment for insomnia or drug use with effects on the central nervous system or metallic implants and/or pacemakers. Of the 26 cases, two were eliminated from the control group, for failing to comply with the age of majority and the second report of phosphenes as a side effect in the first session of the treatment of CES (Fig. 1 shows the eligibility diagram). The final sample included 24 subjects with an average age of 32.10 (± 14. 24) years old (58% women), with a diagnosis of insomnia. Participants were randomized between the control (n = 11) and experimental groups (n = 13) in the order, in which they arrived at the sleep laboratory. No differences in sex and age were observed between the groups.

Figure 1 Flow diagram. 

Results

A difference was found in relation to the sleep habits (p < 0.01) in the experimental group, which reported one more hour of sleep after the intervention (Table 1). There was a significant reduction of four symptoms of insomnia in both groups. In addition, the psychophysiological insomnia symptoms decreased in the control group (p = 0.026) and severity of insomnia in the experimental group (p = 0.002).

In the report of anxiety symptoms, there were no differences between groups, but in depression symptoms, there was a reduction of four points in the control group (p = 0.018) and five points in the experimental (p = 0.016), as shown in table 2.

Based on the analysis of the effect size (Cohen's d), both CES and placebo had a positive effect in reducing the symptoms, but at different levels. For the insomnia index the effect was strong in the CES group (d = 0.88) and moderated in the placebo group (d = 0.52). For symptoms of anxiety, the effect was modest with the CES (d = 0.54) and moderated with placebo (d = 0.35). In both groups the effect size of depression was moderated (d = 0.69, and d = 0.58, respectively).

Discussion

It is suggested that the CES can have positive effects over the symptoms of anxiety, insomnia, and depression due to its influence on the limbic system and the autonomic nervous system, interconnected with the hypothalamic-pituitary-adrenal-immune axis³². However, our results, after low-voltage CES, suggest a variety on the effects on the symptoms of anxiety, depression, and insomnia. In this sense, the increase of an hour of sleep and decrease the severity of insomnia as a result of the CES are observed, but psychophysiological insomnia symptoms reduced as the result of a placebo effect. Symptoms of anxiety and depression decreased in CES group, but they were not superior to placebo group.

The increase in the time dedicated to sleep during the week supports the hypothesis that the CES changed the perception of sleep. However, there are no changes in bedtime schedules and get up to match this increase. Reporting sleeping an extra hour as the effect of the CES was consistent with the results previously obtained¹⁶. It is noteworthy that even with an increase of an hour of sleep (from 5 to 6 h), they are below recommended hours of sleep time³³. Possibly, these results can increase by extending the number of sessions of CES. In addition, it is proposed to consider that the application of the CES should be accompanied by strategies such as hygiene of sleep and therapy cognitive behavior to improve the effectiveness of the CES and maintain longer the positive effects on sleep³⁴.

In relation with insomnia, our results are similar to the results of a meta-analysis study that suggests that the CES is effective for the treatment of insomnia severity³⁵. However, we recommend to obtain objective sleep measurements to establish the physiological mechanism associated with clinical changes. Our results indicate that some types of insomnia such as the psychophysiological may improve as a result of the placebo effect. Psychophysiological insomnia is characterized by concerns over not being able to sleep, occurring particularly at the time of going to bed². Furthermore, it is possible that placebo shifted the focus of attention: the concern to the concentration in the sense of the device, providing relaxation to fall asleep.

In relation to anxiety, some authors have suggested that the CES technique should not be used in the treatment of their symptoms unless that is used for its value as placebo³⁶. In our study, the effect of CES improved the symptoms of anxiety, as it has been reported in the previous studies, but the effect was similar to the placebo's when analyzed the results considering the statistical significance, no statistical differences were observed. Similar results in different studies are discussed based on statistical significance, however, analysis with an alternative statistic as the d Cohen³¹ may be useful to clarify the effect size of intervention with CES and placebo in an independent way.

Whereas the analysis of the effect size, the effect of the CES in the reduction of the severity of insomnia is large and medium in the placebo group. It is confirmed that both statistical significance and effect size had a higher effect of the CES over the placebo. It is possible that CES decreases the cortical hyperarousal, which is characteristic on insomnia; also, CES may increase the alpha activity, facilitating the induction of sleep³⁷.

Furthermore, you can see that the size of the effect on the symptoms of anxiety is medium for the CES and small for placebo which may suggest a reappraisal of the effects of the intervention of the CES to be considered superior to placebo in the treatment of anxiety.

In relation to depression, with the effect size analysis, CES and placebo had moderate effects. Some studies indicate that CES is efficient in an equal or better way than the pharmacological treatment for depression³⁸, but meta-analysis studies indicate that they are scarce systematized double-blind studies³⁹, in this regard, one of them meet this experimental approach, but it did not find differences between CES treatment and placebo⁴⁰. In this sense, our results are consistent with the study that employed the same device of stimulation, both by the statistical significance and effect size calculations; the CES was not superior to placebo in depression symptoms.

The study has some limitations that can focus on two aspects: (1) the size of the sample, to allow extending the statistical analyses, including the segmentation of the sample for analysis by sex and between different levels of severity of symptoms, (2) objective measurements at different levels of analysis both insomnia, anxiety, and depression symptoms (12). Separately, it was analyzed the effect of sleep hygiene and the combination with CES. It is proposed to compare the efficacy of the CES, other treatments, and their combination.

Conclusions

CES is a safe and efficient treatment for insomnia. The analysis of the effect suggests that this treatment can be clinically encouraging for anxiety, but its effect on depression is not superior to placebo.