Dr Mula is Consultant in Neurology and Epileptology at the Atkinson Morley Regional Neuroscience Centre, St George’s University Hospital NHS Foundation Trust and Senior Lecturer at St George’s University, London, UK.
Studies consistently show that depression and mood disorders are comorbid with epilepsy. Data from community-based studies report prevalence rates for mood disorders in 20% to 22% of patients with epilepsy. In selected populations, such as tertiary referral centers or surgery programs, the prevalence is even higher and ranges between 30% and 50%. The wide prevalence ranges seem to be associated with the severity of the seizure disorder. For instance, in patients who are seizure-free, it is estimated only 4% experience depression.1
A complicated relationship
The relationship between depression and epilepsy is complex. A number of epidemiologic studies have suggested that the relationship is not necessarily unilateral but rather bidirectional, with some patients presenting with a psychiatric disorder before the emergence of seizures.2 Such a bidirectional relationship has been noted in other chronic medical conditions such as Parkinson disease, stroke, dementia, diabetes, and cardiovascular disease, which suggests that depression is interlinked with a number of chronic medical conditions.
In the case of epilepsy, various neurobiological and psychosocial variables play a role in this complex relationship. On the psychosocial side, the burden of stigma, social limitations, and the discrimination associated with epilepsy can lead to demoralization and poor self-esteem. On the neurobiological side, the pathophysiology of epilepsy is interlinked with mood problems. Similarly, the involvement of the temporal lobes and the psychotropic effects of antiepileptic drugs seem to be relevant contributors to the increased rates of mood problems in epilepsy.
Children, depression, and epilepsy
Depression has been historically studied and investigated in the context of adult epilepsies, and epidemiological studies of depression in children with epilepsy are limited in comparison. Still, the rates show an increased risk for depression. For instance, a prospective study with a 9-year follow-up of newly diagnosed children with epilepsy reported a 13% prevalence of depression. A large US nationwide survey found depression in 8% of children with current epilepsy, 7% of children with a previous history of seizures, and 2% in control patients.
Similar figures were reported by a UK community-based study of children with epilepsy aged 5 to 15 years who attended schools in Sussex. In addition, 50% of adults with depression usually have a history of an anxiety disorder during childhood.3 For all these reasons it is important to have more data from children with epilepsy.
Getting to the diagnosis
Mood disorders in epilepsy represent a relevant prognostic marker. Depression is not only associated with poor quality of life but also increased rates of adverse effects from medication, increased risk of drug-resistant epilepsy, poor outcomes after surgery, more severe seizures, prolonged post-ictal states, and increased risk of injuries. For this reason, the early detection of mood disorders in epilepsy has considerable implications in the final management of the individual epileptic syndrome.
The phenomenology of depression in patients with epilepsy represented a matter of debate for many years. This point is crucial from a clinical perspective as it implies the need for different clinical instruments to make a diagnosis, different response rates to treatment, the need for different treatment strategies, and ultimately a different prognosis. Although patients with epilepsy develop mood disorders that are identical to those seen outside epilepsy, an increasing number of researchers have pointed out that mood disorders in epilepsy can be characterized by atypical features that are poorly reflected by conventional classificatory systems such as DSM and ICD.
During the 20th century, Blumer coined the term interictal dysphoric disorder to refer to a subtype of somatoform-depressive disorder claimed as typical of patients with epilepsy.4 It was characterized by a component of mood instability associated with anxiety and somatic symptoms. Modern studies pointed out that such a condition is a mood disorder probably not specific to epilepsy, as it is also diagnosed in patients with other neurological problems.
There is also a significant component of comorbid anxiety (social phobia and/or generalized anxiety disorder) and quite evident mood instability. What seems to be typical of patients with epilepsy is the presence of a specific pattern of mood symptoms with dysphoria and mood swings mostly around the seizures. These seem to be responsible for the pleomorphic features of the so-called interictal dysphoric disorder.
All patients with epilepsy should be routinely screened for mood disorders for early identification of any relevant clinical problem. Psychiatric problems are, more often than not, ignored and go untreated, unless they are severe enough to cause major disability. This may be due to the unfamiliarity of neurologists with screening instruments and psychotropic medications used to treat mood disorders.
1. Baker GA, Jacoby A, Chadwick DW. The associations of psychopathology in epilepsy: a community study. Epilepsy Res. 1996;25:29-39.
2. Mula M. Depression in epilepsy. Curr Opin Neurol. 2017;30:180-186.
3. Kim-Cohen J, Caspi A, Moffitt TE, et al. Prior juvenile diagnoses in adults with mental disorder: developmental follow-back of a prospective-longitudinal cohort. Arch Gen Psychiatry. 2003; 60:709-717.
4. Mula M. The interictal dysphoric disorder of epilepsy: a still open debate. Curr Neurol Neurosci Rep. 2013;13:355.
5. Mula M. The pharmacological management of psychiatric comorbidities in patients with epilepsy. Pharmacol Res. 2016;107:147-153.
6. Alper K, Schwartz KA, Kolts RL, Khan A. Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports. Biol Psychiatry. 2007;62:345-54.
Mula M. Neuropsychiatric Symptoms of Epilepsy. New York: Springer; 2016.
Mula M. Depression in epilepsy. Curr Opin Neurol. 2017;30:180-186.
Mula M. The pharmacological management of psychiatric comorbidities in patients with epilepsy. Pharmacol Res. 2016;107:147-153.
Mula M, Kanner AM. Treatment of psychiatric disorders in adults with epilepsy. Epilepsia. 2013;54(Suppl 1):1,2.