Clinical effects of nonconvulsive electrotherapy combined with mindfulness-based stress reduction and changes of serum inflammatory factors in depression

Abstract

BACKGROUND

Depression is a common and serious psychological condition, which seriously affects individual well-being and functional ability. Traditional treatment methods include drug therapy and psychological counseling; however, these methods have different degrees of side effects and limitations. In recent years, nonconvulsive electrotherapy (NET) has attracted increasing attention as a noninvasive treatment method. However, the clinical efficacy and potential mechanism of NET on depression are still unclear. We hypothesized that NET has a positive clinical effect in the treatment of depression, and may have a regulatory effect on serum inflammatory factors during treatment.

AIM

To assess the effects of NET on depression and analyze changes in serum inflammatory factors.

METHODS

This retrospective study enrolled 140 patients undergoing treatment for depression between May 2017 and June 2022, the observation group that received a combination of mindfulness-based stress reduction (MBSR) and NET treatment (n = 70) and the control group that only received MBSR therapy (n = 70). The clinical effectiveness of the treatment was evaluated by assessing various factors, including the Hamilton Depression Scale (HAMD)-17, self-rating idea of suicide scale (SSIOS), Pittsburgh Sleep Quality Index (PSQI), and levels of serum inflammatory factors before and after 8 wk of treatment. The quality of life scores between the two groups were compared. Comparisons were made using t and χ² tests.

RESULTS

After 8 wk of treatment, the observation group exhibited a 91.43% overall effectiveness rate which was higher than that of the control group which was 74.29% (64 vs 52, χ² = 7.241; P < 0.05). The HAMD, SSIOS, and PSQI scores showed a significant decrease in both groups. Moreover, the observation group had lower scores than the control group (10.37 ± 2.04 vs 14.02 ± 2.16, t = 10.280; 1.67 ±0.28 vs 0.87 ± 0.12, t = 21.970; 5.29 ± 1.33 vs 7.94 ± 1.35, t = 11.700; P both < 0.001). Additionally, there was a notable decrease in the IL-2, IL-1β, and IL-6 in both groups after treatment. Furthermore, the observation group exhibited superior serum inflammatory factors compared to the control group (70.12 ± 10.32 vs 102.24 ± 20.21, t = 11.840; 19.35 ± 2.46 vs 22.27 ± 2.13, t = 7.508; 32.25 ± 4.6 vs 39.42 ± 4.23, t = 9.565; P both < 0.001). Moreover, the observation group exhibited significantly improved quality of life scores compared to the control group (Social function: 19.25 ± 2.76 vs 16.23 ± 2.34; Emotions: 18.54 ± 2.83 vs 12.28 ± 2.16; Environment: 18.49 ± 2.48 vs 16.56 ± 3.44; Physical health: 19.53 ± 2.39 vs 16.62 ± 3.46; P both < 0.001) after treatment.

CONCLUSION

MBSR combined with NET effectively alleviates depression, lowers inflammation (IL-2, IL-1β, and IL-6), reduces suicidal thoughts, enhances sleep, and improves the quality of life of individuals with depression.

Key Words: Depression; Nonconvulsive electrotherapy; Mindfulness-based stress reduction; Serum inflammatory factors; Clinical effect; Hamilton Depression Scale

Core Tip: Nonconvulsive electrotherapy (NET) is a promising therapy for depression; however, its clinical effects and underlying mechanisms remain unclear. We conducted a retrospective analysis of data from 140 patients with depression. The control group received mindfulness-based stress reduction (MBSR) therapy, whereas the observation group received a combination of MBSR therapy and NET. Alterations in serum inflammatory factor levels have been observed, suggesting that NET exerts a therapeutic effect by modulating inflammatory levels. This study provides valuable insights for future investigations of the mechanisms underlying the role of NET in depression.

INTRODUCTION

Depression is a common mental health disorder. Its clinical features mainly include continuous and long-term low mood, reduced interest, and decreased energy. The lifetime prevalence rate is 4.9%. It has a high incidence, repeated attacks, high disability rate, and low cure rate[1]. According to one survey, the prevalence of depression in China is approximately 6.8%. The prevalence of major depressive disorder (MDD) is 3.4%[2]. The annual prevalence of depression is increasing, accompanied by an increase in the complexity of treatment[3]. Studies have predicted that, by 2030, the burden of disease caused by depression will top the global list of mental illnesses[4]. Currently, drugs and psychotherapy are the main treatment methods; however, some limitations remain. Therefore, the identification of additional safe and effective treatment methods has become an important global concern.

Mindfulness-based stress reduction (MBSR) is a type of psychotherapy, which focuses on guiding patients consciously and without judgment to perceive the present to alleviate and release negative emotions, enhance psychological well-being, and facilitate patient rehabilitation. To date, satisfactory results have been achieved in clinical applications[5]. Nonconvulsive electrotherapy (NET) is a novel method to improve nonconvulsive electroconvulsive therapy that aims to stimulate brain neurons without causing systemic convulsions[6]. The stimulation intensity of NET is between those of nonconvulsive electroconvulsive therapy and transcranial magnetic stimulation, and the side effects of the treatment are greatly reduced. Studies have shown that subthreshold stimulation without convulsions can achieve the same therapeutic effect as nonconvulsive electroconvulsive therapy[7]. However, there are relatively few studies from China on the use of NET for the treatment of depression. Accordingly, this study aimed to analyze the clinical effects of NET in the treatment of depression and observe the changes in serum inflammatory factors during treatment to provide a new treatment strategy for the clinical practice and enhance patient outcomes.

MATERIALS AND METHODS

General data

In this study, 140 patients with depression were enrolled from the Guangzhou HuiAi Hospital treatment program between May 2017 and June 2022. Based on the treatment method, the patients were divided into an observation group (n = 70) and a control group (n = 70). Criteria for inclusion were: (1) Individuals who fulfilled the clinical diagnostic criteria for depression according to Chinese Classification and Diagnostic Criteria of Mental Disorders-3; (2) age ≥ 18 years; (3) Hamilton Depression Scale (HAMD)-17 score >17; and (4) only MDD without other chronic diseases that affect mood and inflammatory factors. The exclusion criteria were as follows: (1) Previous history of epilepsy; (2) alcohol dependence or drug abuse; (3) serious physical illness; (4) modified electroconvulsive therapy treatment in the past 2 months; and (5) obvious risk of suicide.

Treatment methods

Both groups of patients were administered 10–20 mg escitalopram oxalate qd and did not take any other anti-anxiety, anti-depression, or other drugs. Based on drug treatment, the control group received MBSR treatment, whereas the observation group received mindfulness decompression combined with NET.

MBSR: One psychological consultant with secondary qualifications was the group leader, two third-level psychological consultants were deputy group leaders, and four experienced nursing staff cooperated. (1) Training time: the training time was 8 wk of centralized training. From the first week of admission, the patients chose to undergo treatment at any time of the day; (2) Training environment: A quiet and undisturbed health education room that met the requirements according to the quality control of MBSR, where the therapist introduced the relevant knowledge of MBSR; and (3) Training method: The patients were divided into seven groups according to the time of admission, with 10 patients per group. Each group underwent collective training for 180 min per session. The first 30 min were taught and explained by the doctor, the next 90 min were self-practice sessions, and the last 30 min were group discussions and summaries. The first week mainly comprised mindfulness eating raisins training; body sensation scanning was performed in the second week; the third week comprised mindfulness awareness breathing training; the fourth week included mindfulness stretching exercises; the fifth week comprised 3 min breathing spaces; the sixth week focused on the mindfulness-awareness idea; the seventh week included autonomous mindfulness awareness and experience, and mindful eating; and in the eighth week, all previous exercises were reviewed, summarized, and shared.

NET: Certain parameters were set to control the intensity of the electrical stimulation. The pulse width was 0.5 ms. Current, frequency, and duration were fixed at 0.9 A, 20 Hz, and 0.5-6.0 s, respectively. The setting of the current study was determined according to the age of the patient and was set to 1/8 of the patient’s age. Through a pre-experiment to observe the patient's right lower limb motor convulsions and EEG signals, the current was adjusted to avoid convulsions.

The treatment duration of both groups was 8 wk, and 1-2 times of MBSR were performed every week for 3 h. NET was performed for 30 min, three times a week, with a time interval of less than 2 d.

Observation indicators and evaluation criteria

(1) Comparison of clinical effectiveness and HAMD-17 scores between the groups. Efficacy evaluation: Treatment outcomes for depression were assessed using the HAMD after an 8 wk period[8]. Cured: HAMD score 95%; markedly effective: HAMD score ≥ 8 points, decreased by 70%–95% compared with that before treatment; improvement: HAMD score ≥ 8 points, decreased by 50%–60% compared with that before treatment; ineffective: HAMD score decreased by < 50% compared with that before treatment. The total effective rate was calculated as follows: (cured + markedly effective + improvement )/total number of cases × 100%. A total of 17 items were included in the HAMD scale using a 5-level scoring method of 0 (none) to 4 (extremely severe) points or 0 to 2 points (0: None; 1: Mild-to-moderate; 2: Severe). The severity of the condition increased as the score increased; (2) We used the Pittsburgh Sleep Quality Index (PSQI)[9] to assess the sleep quality of patients before and after treatment. It consisted of 19 self-inspections and five other people's assessments, of which 18 items were categorized into seven factors: Sleep quality, sleep duration, sleep efficiency, sleep disturbances, use of sleep medication, and daytime functioning. Each factor was scored between 0 to 3 points. '0' refers to no difficulty, '3' refers to very difficult, and 21 points is the highest score. A total score ≥ 7 points indicated a sleep disorder. Sleep quality worsened as the score increased and vice versa; (3) The self-rating idea of suicide scale (SSIOS)[10] was employed to assess suicidal thoughts in both study groups prior to and following the intervention. There were 26 items, including four dimensions: optimism, sleep, despair, and cover-up. Possible answers are ‘yes‘ and ‘no.’ Higher scores indicate stronger suicidal ideation. If the total score on the scale is greater than or equal to 12 points, an individual can be considered to have suicidal ideation; (4) We compared alterations in serum inflammatory factors before and after therapy between the two groups. We collected 5 mL of fasting venous blood from all patients before and after eight weeks of treatment. The collected blood samples were then analyzed using ELISA kits to determine the serum IL-1β, IL-6, and IL-2 Levels. The detection steps were conducted meticulously following the instructions provided by the manufacturer (Xinxie Biological XinBio); and (5) Patients’ quality of life was assessed using the World Health Organization Quality of Life-BREF scale[11], which encompasses various aspects of life, including physiological, social, environmental, and emotional fields. The total score is 100 points, with higher scores indicating a better quality of life.

Statistical methods

SPSS software (version 20.0) was used to analyze descriptive variables, including age, HAMD scores, inflammatory factors, and other measurement data. to the data are presented as mean and standard deviation (mean ± SD) t-tests were conducted to compare the groups. The treatment effect, sex, and other count data are presented as [n (%)], and comparisons between groups were performed using the χ² test. Asymptotic significance was determined when the P value was < 0.05.

RESULTS

Comparison of baseline data between the two patient groups

There were no significant differences in baseline data between the two groups (all P > 0.05; Table 1).

Table 1 Comparison of baseline data.

Baseline information	Observer group (n = 70)	Control group (n = 70)	χ2/t value	P value
Sexuality [n (%)]			0.029	0.866
Males	37 (52.86)	36 (51.43)
Females	33 (47.14)	34 (48.57)
Age (mean ± SD/yr)	44.62 ± 9.58	46.37 ± 9.42	1.090	0.278
Course of disease (mean ± SD/yr)	4.39 ± 0.44	4.31 ± 0.65	0.853	0.395
HAMD (mean ± SD/score)	30.88 ± 4.16	29.65 ± 3.72	1.844	0.067

HAMD: Hamilton Depression Scale.

Comparison of HAMD scores before and after treatment

There was no significant difference in HAMD scores between the observation and control groups before treatment (all P > 0.05). After treatment, we compared the HAMD scores between the two groups and found that the observation group exhibited lower scores than the control group (t = 10.280, P < 0.05; Figure 1).

Figure 1 Hamilton Depression Scale score. ^aP < 0.05. HAMD: Hamilton Depression Scale.

Comparison of the clinical efficacy in the two groups

After undergoing treatment for a period of 8 wk, the observation group achieved a significantly higher effective rate of 91.43% in comparison with the control group's rate of 74.29% (t = 21.970, t = 11.700; P < 0.05; Table 2).

Table 2 Comparison of clinical efficacy between the two groups [n (%)].

Groups	Recovery	Effectual	Improvement	Null and void	Total effective rates
Control group (n = 70)	7 (10.00)	14 (20.00)	31 (44.29)	18 (25.71)	52 (74.29)
Observer group (n = 70)	12 (17.14)	20 (28.57)	32 (45.72)	6 (8.57)	64 (91.43)
χ2/t value	8.390				7.241
P value	0.039				0.007

Comparison of SSIOS and PSQI scores in the two groups before and after treatment

Table 3 shows the SSIOS and PSQI scores for both groups which decreased after treatment compared to those before treatment. Additionally, the observation group had significantly lower scores than the control group (P < 0.05).

Table 3 Comparison of self-rating idea of suicide scale and Pittsburgh Sleep Quality Index scores between the two groups before and after treatment (mean ± SD).

Groups	Times	SSIOS/score	PSQI/score
Control group (n = 70)	Before treatment	18.55 ± 4.02	15.83 ± 1.76
	After treatment	0.87 ± 0.12	7.94 ± 1.35
t		36.780	29.760
P value		< 0.001	< 0.001
Observer group (n = 70)	Before treatment	18.88 ± 4.06	15.36 ± 2.54
	After treatment	1.67 ± 0.28a	5.29 ± 1.33a
t value		35.380	29.390
P value		< 0.001	< 0.001

^aP < 0.05 vs the control group after treatment; n = 70.

SSIOS: Self-rating idea of suicide scale; PSQI: Pittsburgh Sleep Quality Index.

Comparison of serum inflammatory factors

After 8 wk of treatment, IL-2, IL-1β, and IL-6 were noticeably reduced in both groups. Moreover, the observation group displayed enhanced levels of serum inflammatory factors compared to the control group (t = 11.840, t = 7.508, t = 9.565; all P < 0.05; Figure 2).

Figure 2 Changes of serum inflammatory factors in two groups of patients. ^aP < 0.05.

Comparison of quality of life between the two groups

After undergoing treatment for 8 wk, the observation group showed a considerably enhanced quality of life compared to that of the control group (P < 0.05; Table 4).

Table 4 Comparison of quality of life between the two groups (mean ± SD).

Groups	Social function	Emotions	Environment	Physical health
Control group (n = 70)	16.23 ± 2.34	12.28 ± 2.16	16.56 ± 3.44	16.62 ± 3.46
Observer group (n = 70)	19.25 ± 2.76	18.54 ± 2.83	18.49 ± 2.48	19.53 ± 2.39
t value	6.983	14.710	3.808	5.790
P value	< 0.001	< 0.001	< 0.001	< 0.001

DISCUSSION

As a prevalent mental disorder, depression is characterized by high recurrence and disability, which greatly hampers patients’ social interaction, body health, and professional ability, consequently burdening society as a whole[12]. Therefore, providing timely and suitable medical interventions for individuals with depression is of immense importance[13,14]. In this study, by observing and comparing the clinical effects of mindfulness decompression alone and mindfulness decompression combined with NET for the treatment of depression, we revealed that the overall effectiveness rate in the observation group was higher than that in the control group, suggesting that the integration of NET with simple mindfulness relaxation techniques could greatly enhance therapeutic outcomes for individuals with depression and further alleviate their clinical symptoms.

The results showed a decrease in the HAMD, SSIOS, and PSQI scores in both groups following treatment, with the observation group exhibiting better outcomes than the control group. After undergoing treatment for 8 wk, the observation group showed a noticeable improvement in their quality of life score compared to the control group. This is because mindfulness decompression therapy enables patients to better deal with negative emotions and stress, and reduces the impact of depression on sleep by cultivating patients’ awareness and acceptance. Additionally, NET treatment improves the metabolic function of brain tissue, helps patients re-evaluate and adjust negative thinking patterns, and promotes sleep. The combination of these can more effectively alleviate depressive symptoms, reduce suicidal ideation, improve sleep quality and quality of life, and help patients recover.

In addition, research has discovered that inflammatory factors influence pathophysiological alterations associated with depression[15]. During the onset of depression, the levels of IL-6, IL-1β, and IL-2 increase, and the activation of immune-inflammatory pathways may affect monoamine and glutamatergic neurotransmission and contribute to the pathogenesis of severe depression in some patients[16-18]. Therefore, inflammatory factors can be used as a reflective index in patients with depression[19,20]. Research has indicated that the upregulation of IL-1β can energize and amplify the central inflammatory response, cause microglial pyroptosis, affect the plasticity of hippocampal synaptic cells, and induce and aggravate depressive symptoms[21]. IL-6 can lead to excessive hypothalamic-pituitary-adrenal activity, which in turn causes fatigue, depression, and neurological symptoms[22]. The findings of this research indicated that the serum IL-1β, IL-6, and IL-2 Levels decreased following treatment in both groups. Additionally, the observation group exhibited notably improved levels of inflammatory factors compared with the control group. This indicates that mindfulness decompression combined with NET has a substantial impact on decreasing serum inflammatory factor levels in individuals with depression. This is because MBSR is a form of psychotherapy that can help patients reduce anxiety and stress and improve their mental state. Reducing psychological stress and negative emotions may reduce the production and release of inflammatory factors. In addition, NET stimulates neuronal activity by transmitting a weak current to the brain, regulates the release of neurotransmitters and the function of the neuroimmune system, and decreases the levels of pro-inflammatory substances.

This study has some limitations. We recruited a small sample of 140 individuals with depression. The selection of participants was limited, and no long-term follow-ups were conducted. In the future, the number of patients should be expanded, and a multicenter and large-sample survey should be conducted through a longitudinal study to further verify the results of this study.

CONCLUSION

Mindfulness decompression combined with NET can ameliorate depressive symptoms and improve sleep quality, effectively alleviate suicidal ideation, reduce inflammatory responses, and improve the quality of life of patients with depression. This combination exhibits remarkable clinical efficacy and deserves widespread clinical adoption.