Comparing pharmacotherapy and transcranial magnetic stimulation for the treatment of anxiety and depression after aortic dissection surgery

Abstract

BACKGROUND

Aortic coarctation is a potentially fatal condition that is primarily treated surgically. Despite successful procedures, patients frequently experience postoperative anxiety and depression, which can hinder recovery and worsen outcomes. Pharmacological interventions, such as 5-hydroxytryptamine (5-HT) and norepinephrine reuptake inhibitors, are commonly prescribed; however, their efficacy alone or in combination with non-invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation (TMS), remains unclear.

AIM

To assess the effect of medications and TMS on post-aortic surgery anxiety and depression.

METHODS

We analyzed the outcomes of 151 patients with anxiety and depression who were hospitalized for aortic dissection between January 2020 and September 2022. Using the random number table method, 75 and 76 patients were allocated to the normal control and study groups, respectively. All the patients were treated using routine procedures. The control group was administered anti-anxiety and anti-depression drugs, whereas the study group was treated with TMS in addition to these medications. The patients in both groups showed improvement after two courses of treatment. The Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) were used to assess anxiety and depression, respectively. The serum levels of brain-derived neurotrophic factor (BDNF) and 5-HT were determined using enzyme-linked immunosorbent assay. The Pittsburgh Sleep Quality Index (PSQI) was used to estimate sleep quality, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function.

RESULTS

The HAMD and HAMA scores reduced in 2 groups, with the study group achieving a lower level than control (P < 0.05). In the control group, 43 patients recovered, 17 showed improvement, and 15 were deemed invalid. In the study group, 52 recovered, 20 improved, and four were invalid. The efficacy rate in study group was 94.74% compared to 80.00% in control (P < 0.05). The BDNF and 5-HT levels increased in both groups, with higher levels observed in the experimental group (P < 0.05). Moreover, the PSQI scores decreased in 2 groups, but were lower in the intervention group than control (P < 0.05). The scores of the RBANS items increased, with the study group scoring higher than control (P < 0.05).

CONCLUSION

Combining anti-anxiety and anti-depressive drugs with repetitive TMS after aortic surgery may enhance mood and treatment outcomes, offering a promising clinical approach.

Key Words: Aortic dissection, Anxiety and depression, Simple anti-anxiety and depression medications, Repetitive transcranial magnetic stimulation, Curative effect

Core Tip: Our study of 151 patients with post-aortic dissection surgery anxiety and depression found that adding repetitive transcranial magnetic stimulation to standard drug therapy significantly improved outcomes, as measured by anxiety and depression scales, serum brain-derived neurotrophic factor and 5-hydroxytryptamine levels, sleep quality, and cognitive function. This combination therapy represents a potent clinical strategy for optimizing postoperative emotional and functional recovery.

INTRODUCTION

Aortic coarctation is a serious condition that can result in mortality in the absence of timely treatment[1]. Although surgery is the primary treatment method for aortic coarctation, patients often experience anxiety and depression to varying degrees after surgery, which can interfere with postoperative recovery and increase postoperative complications, thereby worsening the prognosis[2,3]. Therefore, the timely and effective relief of patients’ negative emotions is extremely important for improving their prognosis. Drugs, including 5-hydroxytryptamine (5-HT) and norepinephrine reuptake inhibitors, are widely used to treat anxiety and depression, among which venlafaxine and duloxetine have proven efficacy[4].

Repetitive transcranial magnetic stimulation (TMS) is a painless and non-invasive treatment modality that involves the stimulation of neurons in the cerebral cortex to regulate emotions. TMS is effective in the clinical management of depression[5,6]. However, few studies have reported the treatment of anxiety and depression using a combination of drug therapy and repetitive TMS. Therefore, this study compared the effects of anti-anxiety and anti-depression drug therapies alone and in combination with repetitive TMS in patients who experienced anxiety and depression following aortic dissection surgery with the aim of providing a new treatment option for this patient population.

MATERIALS AND METHODS

Patients

A total of 151 patients with anxiety and depression who underwent aortic dissection surgery at our hospital between January 2020 and September 2022 were included in this study. The inclusion criteria were as follows: (1) Patients who underwent physical examination, electrocardiography, or computed tomography examination, with surgical indications in line with the Chinese expert consensus on standardized diagnosis and treatment for aortic dissection[7]; (2) patients who met the diagnostic criteria for anxiety and depression in the expert consensus on the diagnosis and treatment of anxiety and depression in general hospitals' postoperatively[8]; and (3) patients who provided informed consent. The exclusion criteria were as follows: (1) Contraindications for surgery; (2) history of mental illness, anxiety, or depression; (3) severe physical illness, organ dysfunction, or other diseases; and (4) refusal to follow the treatment regimen.

Methods

The control group was treated with anti-anxiety and anti-depression drugs as follows: Duloxetine Hydrochloride Enteric Capsules (60 mg) (YaoPharma Co., Ltd.; SFDA approval No: H20213039), starting at an initial dose of 30 mg/day, gradually increasing according to each individual patient’s condition until reaching a maximum dose of 60 mg/day. Sustained-release venlafaxine hydrochloride capsules (150 mg) (Wyeth Pharmaceutical Co., Ltd.; SFDA approval No: J20060016) were administered at an initial dose of 75 mg/day, gradually increasing to a maximum dose of 140 mg/day, in accordance with disease progression.

The study group was provided with the same drug therapy as the controls, in addition to repetitive TMS treatment, which was administered as follows: A transcranial magnetic stimulator (Yiruide) was used, with the center of the coil placed on the dorsolateral side of the left prefrontal lobe of the patient tangential to the scalp. The frequency was set to 10 Hz and the intensity was set to 90% of the exercise threshold. Twenty sequences were performed per day, each lasting 4 s with an interval of 20 second. The treatment course comprised five days of treatment, followed by two days of rest, repeated twice.

Observed indexes

Patients’ anxiety and depression levels were estimated using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD). Both scales were scored on a five-point scale from 0-4, as follows: 0, no symptoms; 1, mild symptoms; 2, moderate symptoms; 3, severe symptoms; 4, very severe symptoms. Higher scores indicated worse anxiety and depression.

The treatment efficacy was evaluated using the HAMA and HAMD scales[9]. Treatment was classified as ‘effectual’ if symptoms disappeared, HAMA and HAMD scores decreased by > 50%, and no adverse reactions occurred. Treatment was classified as ‘improved’ if symptoms improved, HAMA and HAMD scores decreased by 25%-50%, and mild adverse reactions developed. The protocol was considered ineffective if there was no significant improvement in symptoms or if it required adjustment.

Fasting venous blood samples were collected from the patients to allow for the measurement of the serum levels of brain-derived neurotrophic factor (BDNF) and 5-HT using enzyme-linked immunosorbent assays. Sleep quality was estimated using the Pittsburgh Sleep Quality Index (PSQI)[10], which comprises seven items and 18 entries. A higher total score indicated a lower quality of sleep.

Cognitive function was appraised by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)[11]. The Chinese version of the RBANS consists of 12 items: vocabulary memory, story memory, graphic description, line angle, image naming, language fluency, numerical breadth, coding, vocabulary recall, vocabulary recognition, story recall, and graphic recall. The scores were proportional to cognitive function.

Statistical analysis

SPSS20.0 software was used for data analysis. The HAMA and HAMD scores are expressed as the mean ± SD, and Student’s t-test was employed for comparisons. The efficacy rates of treatment are expressed as percentages, and comparisons were made using the χ² test. Statistical significance was set at P < 0.05.

RESULTS

Data comparison

After grouping using the random number table method, 75 cases were classified as controls, of whom male (49 cases) and female (26 cases), the average age was 66.12 ± 6.13 years (range, 48-76 years). The course of the illness lasted for 1–7 days (mean, 3.31 ± 0.68 days). This group included 39 stanford type A and 36 stanford type A and B cases, respectively. A further 76 patients (51 men and 25 women) were classified into study group. The average age was 66.37 ± 6.45 years (range, 46-77 years). The course of illness varied from 1 to 7 days, with a mean of 3.49 ± 0.72 days. There were 36 stanford type A and 40 stanford type A and B cases, respectively. No significant differences in the baseline characteristics were observed between the two groups (P > 0.05).

Analysis of anxiety and depression

There were no appreciable differences in the pre-treatment levels of anxiety and depression between the groups (P > 0.05). The HAMA and HAMD scores declined in both groups post-treatment, with the scores of the intervention group decreasing less than control (P < 0.05; Table 1).

Table 1 Analysis of anxiety and depression in both groups (mean ± SD, points).

Group	n	HAMA		HAMD
		Before treatment	After treatment	Before treatment	After treatment
Control group	75	26.95 ± 3.14	16.99 ± 3.07	27.08 ± 7.03	19.53 ± 4.95
Study group	76	26.63 ± 3.86	14.53 ± 2.11	28.13 ± 7.01	17.21 ± 5.34
t value		0.549	5.744	0.919	2.770
P value		0.584	< 0.001	0.360	0.006

Curative effect analysis

In the control group, 43 cases were deemed effectual, 17 improved, and 15 ineffective. In the study group, 52 cases were deemed effectual, 20 were improved, and 4 were ineffective. The efficacy rate was 94.74% (72/76) in study group, which was higher than control (80.00%, 60/75; P < 0.05) (Table 2).

Table 2 Curative effect analysis in both groups.

Groups	n	Effectual	Improved	Ineffective	Effective rate (%)
Control group	75	43	17	15	80.00
Study group	76	52	20	4	94.74
χ2					7.453
P value					0.006

Serum index analysis for both groups

Before therapy, the differences in the BDNF and 5-HT levels between 2 groups were not statistically obvious (P > 0.05). After therapy, BDNF and 5-HT levels were elevated in 2 groups; however, the levels in study group were higher than control (P < 0.05; Table 3).

Table 3 Serum index analysis for both groups (mean ± SD, ng/mL).

Group	n	BDNF		5-HT
		Before treatment	After treatment	Before treatment	After treatment
Control group	75	23.46 ± 4.26	29.17 ± 3.29	44.16 ± 6.40	68.21 ± 10.57
Study group	76	23.43 ± 4.17	31.27 ± 3.41	44.08 ± 6.48	78.56 ± 11.28
t value		0.044	3.850	0.076	5.816
P value		0.965	< 0.001	0.939	< 0.001

5-HT: 5-hydroxytryptamine.

Sleep quality analysis

Before therapy, no significant differences were observed in sleep quality between the 2 groups (P > 0.05). Post-treatment, the PSQI scores declined in 2 groups, with scores in study group being lower than comparison group (P < 0.05; Table 4).

Table 4 Sleep quality analysis in both groups (mean ± SD, point).

Group	n	Before treatment	After treatment
Control group	75	13.28 ± 1.74	9.39 ± 1.27
Study group	76	13.26 ± 1.67	7.20 ± 1.03
t value		0.061	11.615
P value		0.952	< 0.001

Cognitive function analysis

No apparent discrepancy was observed in pre-therapy cognitive function between the two groups (P > 0.05). After treatment, the RBANS scores increased, with the intervention group showing higher scores than the control group (P < 0.05; Table 5).

Table 5 Cognitive function analysis for both groups (mean ± SD, point).

Group	n	Attention		Immediate memory		Delayed memory		Visuospatial		Language		Aggregate score
		Before treatment	After treatment	Before treatment	After treatment	Before treatment	After treatment	Before treatment	After treatment	Before treatment	After treatment	Before treatment	After treatment
Control group	75	93.36 ± 2.64	94.75 ± 1.73	81.35 ± 6.63	90.75 ± 2.36	88.61 ± 5.73	95.12 ± 2.13	90.15 ± 1.34	92.53 ± 1.35	87.63 ± 3.63	93.41 ± 2.15	441.09 ± 10.09	466.56 ± 4.71
Study group	76	93.42 ± 2.71	97.28 ± 0.69	81.28 ± 6.57	96.58 ± 1.47	88.57 ± 5.62	99.25 ± 0.66	90.18 ± 1.26	95.49 ± 1.61	87.61 ± 3.53	96.07 ± 2.04	441.05 ± 8.88	484.66 ± 3.01
t value		0.14	11.825	0.066	18.245	0.051	16.142	0.177	12.2	0.037	7.774	0.026	28.194
P value		0.889	< 0.001	0.948	< 0.001	0.959	< 0.001	0.86	< 0.001	0.971	< 0.001	0.979	< 0.001

DISCUSSION

Aortic dissection occurs after the tearing of the aortic intima, leading to the flow of blood in the aortic cavity into the aortic media, causing the media to separate and expand. If treatment is not performed rapidly, this condition can affect the circulatory system, seriously affecting other important organs and even proving fatal[12,13]. The occurrence of aortic dissection is related to several factors, including arteriosclerosis and connective tissue diseases. This condition is most common in middle-aged and elderly populations (50-70 years), with a predominance among males[14]. Currently, the primary clinical treatment for aortic dissection is surgery, which can efficiently improve the patients' symptoms and enhance their quality of life. However, patients have been found to be prone to developing anxiety and depression post-surgery, which can hinder their postoperative recovery. Although depression is known to be associated with several factors, there are currently no clear clinical conclusions regarding its pathogenesis. Nevertheless, at present, the predominant theory is that which proposes monoamine neurotransmitter disorders as causative factors. In this context, the majority of researchers believe that central neurotransmitters, such as 5-HT, are related to dopamine expression levels. Therefore, at present, drug therapy is the primary treatment option for anxiety and depression.

Venlafaxine and duloxetine are commonly used for the clinical treatment of anxiety and depression. The anti-anxiety mechanism of these drugs involves the activation of the 5-HT receptor, while their antidepressant effect involves the reduction of the 5-HT receptor. These drugs bind to 5-HT receptors in the middle lateral suture zone of the brain, resulting in significant clinical effects[15,16].

Repetitive TMS is a biological stimulation technology that can alter brain function. Its mechanism of action primarily involves effects on the cerebral cortex, the formation of induced currents, and the fulfillment of its role in the action potential of cortical nerve cells. Furthermore, the combination of drug treatment with repetitive TMS has been shown to have a significant clinical effect, effectively reducing the severity of anxiety symptoms in patients[17,18].

In the present study, the HAM-A and HAM-D scores markedly decreased post-treatment in both groups, with the scores in study group being lower than control. Furthermore, the efficacy rate was higher in experimental group than control, indicating that combined treatment with drugs and repetitive TMS can successfully mitigate negative emotions and improve clinical symptoms.

BDNF primarily plays a role in neuronal synthesis and axoplasmic transport and can repair and protect neurons. Furthermore, in accordance with the monoamine neurotransmitter disorder theory, 5-HT levels can also be used as an indicator to evaluate depression rehabilitation. In our study, we found that the BDNF and 5-HT levels were elevated in 2 groups post-treatment, indicating the effective anti-anxiety and anti-depressive effects of the two treatment modalities. However, the levels of BDNF and 5-HT in study group were higher than control, suggesting that drug therapy combined with repetitive TMS was superior to drug treatment alone. The current induced by the pulsed magnetic field was used to stimulate the patient’s cerebral neurons to improve the functionality of the cerebral cortex.

Anxiety and depression are associated with a wide range of symptoms, including insomnia. In this study, we found that sleep disorders in an elderly population were associated with the risk of depression. Indeed, the sleep quality of the patients in both groups was found to be poor. However, after drug treatment, the sleep quality of patients improved, suggesting that anti-anxiety and anti-depression drugs can enhance sleep quality. However, the PSQI score of patients after drug therapy combined with repetitive TMS treatment was even better, indicating that stimulating the cerebral cortex can also promote sleep[19]. Following the implementation of repetitive TMS, the cognitive function score of study group was higher than control, indicating that the combined therapy improved cognitive function, possibly because TMS can excite or inhibit the cerebral cortex function through the application of different frequencies, thus exerting a two-way regulatory function in the brain. The use of repetitive TMS has also been shown to significantly improve cognitive function through intensive treatment of different regions of the brain, in a manner dependent on treatment intensity, frequency, and coil direction[20]. Our study had some limitations. The sample size of participants was insufficient which may cause bias of the results. And future studies should consider increasing the sample size.

CONCLUSION

To summarize, our findings suggest that anti-anxiety and anti-depressive drugs combined with repetitive TMS treatment may improve sleep quality and cognitive function and alleviate negative mood in patients with anxiety and depression following aortic dissection surgery. Therefore, these results highlight this therapeutic combination as a promising option for the clinical treatment of depression and anxiety.