Anxiety and depression are the most common combined psychological disorders in patients with epilepsy, especially in patients with long-term uncontrolled seizures. Anxiety and depression are also one of the main causes of decreased quality of life in patients with epilepsy.
1. Incidence of epilepsy combined with anxiety and depression
In recent years, several large-scale population-based and clinical epidemiological studies of epilepsy in foreign countries have shown that the incidence of combined depression in epileptic patients (10%-60%) is significantly higher than that in the general population, especially in patients with intractable epilepsy with uncontrollable long-term seizures. Delay found suicidal attempts in 112 (34.56%) of 324 hospitalized patients with epilepsy.
In a survey of 909 randomly selected patients with epilepsy, Janz showed that 11 died of suicide without convulsive seizures for a short period of time before suicide, and Bruns showed that 6 patients had severe suicide attempts in 220 patients. In contrast, 81% to 100% of epileptic patients who committed suicide had a comorbid psychological disorder, the majority being comorbid depression.
Although the incidence of comorbid anxiety in patients with epilepsy is also high, epidemiological data on large models of comorbid anxiety in epilepsy are scarce.
In China, no large-scale population-based and hospital-based clinical epidemiological surveys on anxiety and depression in epilepsy have been conducted. In a survey of 50 patients with epilepsy by Xiang Daiqun et al. using a depression self-rating scale, the incidence of depressive disorder was 20%. Li Yumei et al. scored HDRS in 60 patients and 15 cases, accounting for 25% of the total number of patients, met the diagnosis of depression.
In a hospital-based study, a survey of 80 patients with long-term uncontrolled seizures showed that about 45% had depressive mood and 25% had anxiety, and 90% of them had anxiety with depressive mood. This result is similar to that reported in foreign literature. Both findings suggest that the prevalence of comorbid anxiety-depression disorders in patients with epilepsy is quite high.
Studies have shown that depressive mood is a major cause of suicide in patients with epilepsy more than three times higher than in the general population. Therefore, psychological disorders in patients with epilepsy should be identified in a timely manner, and patients with psychological problems should be given early and active treatment.
2. Etiology and pathogenesis of epilepsy combined with anxiety and depression
Recent studies have confirmed that there is a significant correlation between epilepsy and anxiety and depression, but so far, the etiology and pathogenesis of epilepsy combined with anxiety and depression are not fully understood. The long-held belief that anxiety and depression may be a “normal” response in patients with epilepsy has recently shifted to the belief that epilepsy combined with anxiety and depression may be related to a variety of factors, including genetic, neurological, and medical factors.
The incidence of comorbid depression is higher in patients with epilepsy who have a family history of depression. All of these studies suggest that there may be a genetic relationship between epilepsy comorbid depression.
There may be a common neurobiological pathogenesis of epilepsy and anxious depression. Studies suggest that structural abnormalities in the frontal and temporal lobes and reduced secretion of neurotransmitters (gamma-aminobutyric acid, 5-hydroxytryptamine, norepinephrine and dopamine) in the brain are jointly involved in the development of epilepsy and anxiety depression. Many regions of the brain that cause seizures are involved in the expression of fear, in which the amygdala is thought to play a key role, and anxiety depression is thought to be based on a conditioned emotional association with the amygdala.
And this overreaction may be related to a failure of inhibitory regulation in the amygdala. Further structural and functional neuroimaging studies in humans confirm that anxiety or panic disorders are closely related to abnormalities in the amygdala, and more than 50% of epileptic patients with MRI showing amygdala atrophy exhibit fear. Experimental animal studies have shown that γ-aminobutyric acid, 5-hydroxytryptamine, norepinephrine and dopamine are involved in the ignition of epileptic foci and exacerbate seizures. γ-aminobutyric acid is the major depressive neurotransmitter in the central nervous system and is balanced by the excitatory effects of glutamatergic neurotransmission.
Glutamatergic hyperexcitability appears in seizures and is also thought to play a role in pathological anxiety and may be manifested through the conditioned fear-associated overreaction described above.
In addition, clinical pharmacology studies have found that γ-aminobutyric acidergic antiepileptic drugs have concomitant anxiolytic-depressive effects. All of these findings support the possibility that epilepsy and anxiety-depression share a common pathogenesis and that the two may contribute to each other, with one condition exacerbating the other and exacerbating the other.
Medical factors may also contribute to the development of anxiety-depression disorders in patients with epilepsy. Medication effects are an important risk factor for depression in combination with epilepsy. Antidepressant medications can lower the seizure threshold. As a result, physicians are reluctant to choose antidepressants for patients with epilepsy who are depressed, which can worsen their depression. Some drugs, including antiepileptic drugs, can also cause depression, such as phenobarbital, which is closely related to behavioral changes and depression, and other antiepileptic drugs that can reduce the level of folate in the body, which can also lead to the occurrence of depression.
3, epilepsy combined with the influence of anxiety and depression factors
Hermann et al. divided the potential influencing factors into four categories, namely neurological (age of onset, lesion location, duration, etiology, and seizure type), psychosocial (epilepsy awareness, distress, discrimination, and stress), pharmacological (monotherapy, polypharmacy, and plasma drug concentration levels), and sociodemographic (age, gender, and education).
Frequency and severity of episodes had a significant impact on patients’ anxiety and depression. Seizure frequency was the most important predictor of psychological disorders and correlated significantly with psychological disorders .Bake et al. A comparative study of two groups of patients with controlled and uncontrolled seizures (>1 seizure/month) found that anxiety-depressive symptoms were significantly higher in the uncontrolled group than in the controlled group.
Domestic literature reported that after 3 months of standardized treatment in 80 patients with irregularly treated and long-term uncontrolled seizures, the frequency of seizures was significantly improved, as well as the anxiety and depression. Meanwhile, multifactorial regression analysis suggested that seizure severity was an independent risk factor for combined anxiety and depression in epilepsy patients, suggesting that seizure control is one of the key factors to improve psychological disorders in epilepsy patients.
In a study of 20 patients with epilepsy combined with depression, Mendez et al. showed that 16 of them had complex partial seizures, and 10 of the 11 cases with abnormal EEG discharges were located on the left side. . However, there are different reports that suggest that the relationship between anxiety and depression and site is not obvious. In conclusion, the relationship between the site of discharge and the site of organic brain damage, etc. and anxiety-depression has been reported differently in the literature and may be related to a variety of factors, which needs to be confirmed by further studies.
The effect of antiepileptic drugs on anxiety and depression is biphasic. Some antiepileptic drugs can exacerbate anxiety-depression in patients (e.g., phenobarbital), while patients with epilepsy who have a history of mood disorders can exacerbate some of the side effects of antiepileptic drug mood disorders, but the mechanism of action is unclear. Other antiepileptic drugs can improve anxiety and depression, such as sodium valproate, gabapentin, and tiagabine all have varying degrees of improvement on mental disorders.
Currently, these antiepileptic drugs with ameliorating effects on anxiety and depression have been widely used in the treatment of mood disorders and have become the first-line therapeutic agents for bipolar disorder. The mechanism of action may be based on recently developed concepts regarding the fear circuitry in the brain. These antiepileptic drugs regulate the levels of γ-aminobutyric acid and glutamate in the central nervous system, restoring the dynamic balance between the two transmitters and thus reducing the hyperexcitability of neurons (especially the amygdala).
The exact mechanism of the anxiolytic action of sodium valproate is unclear, and it is speculated that it may be related to increasing the level of γ-aminobutyric acid in the brain. Gabapentin promotes the secretion of nonsynaptic γ-aminobutyric acid from glial cells, thereby decreasing neuronal excitability. Carbamazepine blocks voltage-gated sodium channels in neuronal cell membranes, which in turn prevents the release of excitatory neurotransmitters from neural uncircumstances.
Topiramate has multiple mechanisms of action, enhances γ-aminobutyric acid activity, antagonizes glutamate, and blocks voltage-gated sodium channels, and is also a weak depressant of carbonic anhydrase isoenzymes. Tiagabine is the only selective γ-aminobutyric acid reuptake inhibitor currently on the market. Lamotrigine exerts its efficacy through the action on voltage-sensitive sodium channels and the subsequent inhibition of glutamate and aspartate. Aminoglutethimide is a specific γ-aminobutyric acid conversion acid inhibitor.
Studies have shown that age and gender may have an effect on anxiety, with anxiety becoming more pronounced in adults the later the age of onset. There are differences in the literature on the effect of gender on anxiety and depression in patients with epilepsy; Souza et al [4] reported no significant effect of gender on anxiety and depression in patients with epilepsy, while a study by domestic scholars showed that anxiety was more pronounced in men with epilepsy than in women and became one of the independent risk factors affecting anxiety in men, while there was no significant gender difference in depression.
The analysis suggests that this difference may be related to the perception of men’s status in society, as men believe that they are the main body of society, and once they have epilepsy, their social function will be limited to a certain extent, so their anxiety is greater than that of women.
In addition, some domestic scholars’ research results show that education, economic status, disease duration, marriage, and residence have some influence on patients’ anxiety and depression, and those with high education, good economic status, unmarried and living in cities have relatively light anxiety and depression. The longer the duration of the disease and the more severe the attack, the more pronounced the patient’s anxiety and depression.
The results of this study are different from those of foreign countries. The analysis suggests that the different national and cultural backgrounds have led to different perceptions of epilepsy and treatment in different populations, resulting in different levels of anxiety and depression in different populations of epileptic patients.
4. The impact of anxiety and depression on the quality of life of epilepsy patients
Due to the effects of epilepsy itself, long-term medication side effects and seizures, the quality of life of people with epilepsy is significantly reduced and the incidence of anxiety and depression is significantly increased. In a study of 435 outpatients with epilepsy, Tracy et al. showed that the lower the anxiety-depression score, the higher the patient’s quality of life score, and that anxiety-depression directly affects the patient’s quality of life, independent of other factors.
Meldolesi et al. The results of a study of 106 patients with refractory temporal lobe epilepsy showed that anxiety and depression affected multiple aspects of quality of life, and the severity of anxiety and depression was closely related to low scores in all aspects of quality of life, making it the most powerful predictor of good or bad quality of life in epilepsy patients.
5. Treatment of epilepsy combined with anxiety and depression
For a long time, the diagnosis and treatment of epilepsy combined with anxiety and depression have not received sufficient attention. Anxiety and depression, like epilepsy, is a chronic process with an unpromising long-term prognosis and the possibility of recurrence. Although it is believed that epilepsy puts patients at significantly increased risk for anxiety and depression, many studies have confirmed that anxiety and depression are a risk factor for seizures and that early diagnosis and aggressive treatment of epilepsy combined with anxiety and depression is important.
Some studies have shown that without treatment, the duration of depression typically lasts 6-13 months, while the duration of depression can be reduced to 3 months in patients who receive active treatment.
In patients with epilepsy combined with anxiety and depression, it is important to first explain the condition, gain the patient’s understanding, be able to actively cooperate with antiepileptic treatment, and if necessary, give anti-anxiety and depression treatment. Although there are many ways to treat anxiety and depression, the most critical treatment for patients with epilepsy combined with anxiety and depression is to control the seizures first.
Otherwise, the effectiveness of treatment for anxiety and depression is minimal. In addition to seizure control, the treatment for anxiety and depression mainly includes medication and psychotherapy. Anti-anxiety-depression medications are available for patients with significant anxiety-depression. Selective 5-hydroxytryptamine reuptake inhibitors (SSRI) (such as paroxetine, sertraline, fluoxetine, fluvoxamine, etc.) are the first-line medications for anxiety depression, and other medications such as benzodiazepines and buspirone can also be used.
However, it has been found that not all patients with anxiety and depression can be cured after receiving medication. The recovery rate of depressed patients after antidepressant treatment is about 60% to 70%, but if the treatment is not maintained afterwards, more than half of the patients will relapse in the next 5 years. Therefore, exploring new treatment methods to improve the effectiveness of anxiety and depression treatment has become a concern for researchers. Current research suggests that the efficacy of psychotherapy for anxiety and depression is positive, especially cognitive psychotherapy.
Ninan et al. concluded that cognitive-behavioral therapy (CBT) is more effective than medication in treating anxiety and depression because psychotherapy can prevent recurrence of depression.
In conclusion, the incidence of combined anxiety and depression in patients with epilepsy is high, and there are many potential factors that affect anxiety and depression in patients with epilepsy.