At the recent ILAE Europe Epilepsy Congress 2022, Professor Kette Valente delivered a presentation on recommendations for the diagnosis and treatment of depression for children with epilepsy, and Dr. Marco Mula presented on the possibility of taking antidepressants, as recommended by healthcare providers, in treating adults with epilepsy.

 

Background

Approximately 1 in 8 children have mental disorders at any given time.¹ According to Prof. Valente, “the prevalence of pediatric epilepsy is 5-6 times higher than the average population [of any depressive disorder].”² Meanwhile, Dr. Mula also highlighted that “1 in 4 adults with epilepsy have active depression (referring to actively symptomatic in the last 12 months), which is about 3 times higher than that in general population.”³

 

Case study

Prof. Valente began the presentation with a case study of a 10-year-old girl with typical absence seizures and prescribed ethosuximide with complete seizure control in the past 2 years. Her mother reported that her daughter has lately remained emotionally sad, quiet and careless about her appearance. Healthcare providers then suggested the following options: referring the girl to a mental healthcare provider, screening for behavioral disorders to compare to her baseline state, screening for depression since the patient has a complaint, and/or replacing ethosuximide with valproate.  

 

The process of screening for mental disorders

Screening for mental disorders is an assessment process which involves conducting clinical interviews with various sources at the right time. Depression (23%) and suicidality (14%) have been demonstrated in children and adolescents with epilepsy.⁴ Therefore, children should be screened systematically and routinely in their first appointment. Variables such as previous and family history of psychiatric disorders, frequency of somatic complaints, suicide-related behaviors, substance abuse, trauma and psychosocial stressors should be factored into the assessment.⁵

A child’s functioning and psychosocial well-being are highly dependent on the environment of the home and school.⁶ Obtaining a full and accurate diagnostic picture of a child will require collection of information from diverse sources, ranging from the child themselves, their family, school, and other agencies involved with the child.⁶ It is also advised to interview the child’s parents at least, if possible.

In the psychiatric interviews, a formal screening questionnaire is recommended as the first-level screening to assess for symptoms of depression in children and adolescents with epilepsy. A global behavioral assessment helps give an overview of a child’s condition. The most frequently used checklist is the Child Behavioral Checklist (CBCL). Please see the pros and cons of clinical psychiatric interviews in table 1.⁷

Table 1. Pros and cons of clinical psychiatric interviews

DSM: Diagnostic and Statistical Manual of Mental Disorders; ICD: International Classification of Diseases
 

Rating scales may also be used for assessment as they are more specific for depression and anxiety. The most frequently used scale in pediatric epilepsy is the Children’s Depression Inventory (CDI), which addresses emotional problems and functionality. However, given the high risk of bias, the scales provide a very low strength of evidence.^8-12

Noting that the child being assessed has epilepsy, it is important to determine if the child is in the pre-ictal, ictus, post-ictal or inter-ictal phase of a seizure.¹³ A spectrum of behaviors and psychiatric disturbances can occur throughout the phases of a seizure (figure 1).¹³

 

Figure 1. The spectrum of behavioral and psychiatric disturbances that can occur throughout different phases of a seizure

 

Continuing the case study

After screening the patient, mild depressive symptoms with an impact on sleep and functionality impairment (e.g. academic performance and peer interaction) were detected. The healthcare provider then suggested the following options: referring the patient to a mental healthcare provider, providing psychoeducational treatment, starting a pharmacological treatment, and/or referring the patient for psychotherapy.

To determine an appropriate therapy, the treatment should be considered as part of a staged approach, which includes a pragmatic treatment plan, watchful monitoring, active treatment and referral. During the pragmatic planning stage, a therapeutic alliance among the children/adolescents with epilepsy, their family members and the healthcare providers should be established so that the goals and plans can be set appropriately. Watchful monitoring is conducted every week for 6-8 weeks in cases of mild depression, and behavioral activation techniques (e.g., exercise and leisure activities) may be employed. The non-pharmacological treatment includes psychotherapy in the form of cognitive behavior therapy (CBT), while therapeutic supportive measures under CBT include family therapy, psychoeducational intervention and physical activity.^14-17 Pharmacological treatment options for children with epilepsy include sertraline and fluoxetine.¹⁷ Of note, these treatments have not been observed to increase seizure frequency.¹⁸

For moderate and severe depressive disorders, active treatment is immediate without watchful monitoring. A combination of selective serotonin reuptake inhibitors (SSRIs) and psychotherapy is recommended by mental healthcare providers.

Intervention pathways for depression in epilepsy

Dr. Mula then continued the symposium, diving deep into depression and its treatment with antidepressants in adult patients with epilepsy. He discussed the practical points of developing intervention pathways for depression in epilepsy.

The first step is to have a plan for identification, risk assessment and active monitoring (e.g., residual symptoms, relapse and recurrence prevention). Currently, there are several screening instruments that can be used and have been validated in patients with epilepsy. The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) scale, which is specifically developed for people with epilepsy, is the most frequently adopted assessment tool and the quickest one to provide results (table 2).^19,20

Table 2. Depression-screening tools validated in adults with epilepsy and psychometric properties

BDI-II: Beck Depression Inventory-Second Edition; HADS-D: Hospital Anxiety and Depression Scale-depression Subscale; HRSD-17: Hamilton Rating Scale for Depression 17-item Version; NDDIE-E: Neurological Disorder Depression Inventory for Epilepsy; NPV: Negative predictive value; PHQ-9: Patient Health Questionnaire 9; PPV: Positive predictive value

 

The second step is to advise on sleep hygiene and physical activity (low intensity), in addition to   the recommended low-intensity psychological interventions (e.g., psychoeducational groups, self-help, and computerized CBT). The third and fourth steps involve high-intensity psychological interventions (e.g., CBT, in-patient therapy, counseling) and prescribing antidepressants.

 

Barriers to the treatment of depression in epilepsy

There are barriers to the treatment of depression in adult with epilepsy, like double stigma, inadequate resources in mental health, the lack of training of neurologists and psychiatrists, misconceptions about the seizure risks with antidepressants, and the lack of guidelines.²¹

Guidelines for the treatment of depression in epilepsy vary from country to country, and notably there is an absence of guidelines in some countries. Against this backdrop, a commission developed a very basic ILAE clinical practice recommendations document for the medical treatment of depression in adults with epilepsy, providing a worldwide theoretical framework on how to approach the pharmacological treatment of depression in epilepsy.²² This framework should be adapted to the local guidelines to champion access to care for people with epilepsy and depression. 

 

The ILAE clinical practice recommendations for the medical treatment of depression in adults with epilepsy

Dr. Mula focused on 4 areas of the recommendations, namely first-line treatment, special precautions, treatment duration, and other treatments.²² SSRIs are noted as the first-line treatment class, on the basis that they offer a balance between efficacy and tolerability (i.e., side effects). SSRIs act not only on serotonin receptors, but are also partially dopaminergic, noradrenergic, or antihistaminergic. Since SSRIs can interact with a variety of receptors, they may display a variety of side effects.

When treating severe depression, special precautions with consideration of the risk of overdosing and suicide attempts should be taken into account.^22,23 Additionally, SSRIs are not associated with seizure worsening in people with epilepsy, unlike some drugs like clomipramine which may increase the risk of seizures.²²

Guidelines for the treatment of depression maintain that antidepressant treatment should be continued for 6 months after the first depressive episode, and 9 months in patients experiencing the second or third episode, or until the patient’s residual symptoms have subsided.²²

Other treatments include vagal nerve stimulation (VNS) and transcranial magnetic stimulation (TMS), with an alternative treatment option being hypericum (St. John’s Wort).²² Hypericum may be perceived as an appealing natural remedy; however, seizures are a potential side effect, and hypericum may interact with other anti-epileptic medications, and so it is not included in the recommendations.²²

 

Conclusion

Prof. Valente concluded with a message supporting the child patient with epilepsy, “minimizing extra burden and the double stigma, ensure acceptance, and assure adherence to treatment and counseling. ” In the question and answer session, Dr. Mula furthered that “We should not ignore the complexity and complex need of people with epilepsy. We need to continuously make improvements”.