Epilepsy and Depression – A Bi-directional Relationship
Assessing the prevalence of depression from selected clinical samples of patients with epilepsy shows a bias towards the more severely affected subjects. A better understanding of co-morbid psychopathology comes from community studies. Edeh and Toone³ carried out a general practice study in the UK and reported that 22% of unselected patients with epilepsy were diagnosed as having a depressive disorder. A Canadian Community Health Survey (CCHS) examined 253 people with epilepsy using a rating scale to identify a history of depression. The authors noted a 22% lifetime prevalence of depression that was much higher than the 12% prevalence rate reported in the general population.⁴

More recently, Ettinger et al.⁵ assessed depression in 775 subjects with epilepsy and compared the prevalence rates with those of patients with asthma and with healthy controls. In this study a rating scale assessment was also used (the Center For Epidemiological Studies – Depression Scale [CESD]). Symptoms of depression were significantly more frequent in the epilepsy group (36.5%) compared with those with asthma (27.8%) and controls (11.8%).

Several studies have noted a correlation between depression and seizure frequency. In an epidemiological study, Jacoby et al.⁶ noted that depression occurred in 4% of seizure-free patients and in 10% of patients suffering less than one seizure a month, but at a rate of 21% in patients with higher seizure frequency. O’Donoghue et al.⁷ noted that patients with epilepsy and continuing seizures were significantly more likely to suffer from depression than those in remission (33 versus 6%).

There are a number of studies from selected patient groups that noted an even higher frequency of depression in these populations. Victoroff et al.⁸ evaluated 60 patients with intractable complex partial seizures using a structured clinical interview from the Diagnostic and Statistical Manual of Mental Disorders 3rd Edition (DSM-IIIR), and observed that 58% had a lifetime diagnosis of depressive disorders. Jones et al.⁹ examined 199 patients from five epilepsy centres, again using a structured clinical interview, the Mini International Neurophychiatric Interview (MINI), and noted that 34% met diagnostic criteria for a mood or anxiety disorder and 19% met criteria for major depression. Ring et al.¹⁰ examined 60 patients awaiting temporal lobe epilepsy surgery, and reported at pre-operative assessment that a major depressive disorder was present in 21%. Taken together, these data suggest that epilepsy and depression are frequently linked, and that the association is more common than in some other chronic medical conditions. Moreover, this relationship seems to be stronger in those with higher seizure frequencies and with continuing seizures. Thus, the presence of depression can be said to be even higher in selected populations, in particular in patients with difficult-to-treat or drugresistant seizures.

A verified finding is the association between depressive symptoms and quality of life (QOL) in people with epilepsy. Gilliam et al.¹¹ noted depression to be the most important predictor of QOL, being a more powerful predictor than the actual seizure frequency. Perrine et al.¹² and Boylan et al.¹³ have reported similar findings.

An interesting finding is that the relationship between epilepsy and depression is not necessarily unidirectional. Patients with co-morbidity do not always present with the seizure disorder before the emergence of the depression. In fact, it has been noted in epidemiological studies that having a prior mood disorder can be associated with an increased risk of epilepsy.^14,15 There may be a number of reasons for this, including the use of proconvulsive antidepressants and the development of epilepsy following suicidal attempts, drug abuse or some other trauma (e.g. head trauma). However, these findings may reflect on an underlying common pathogenesis, which may relate to an as yet unknown genetic factor or a link with neuro-transmitter function. Certain transmitters, such as serotonine, glutamate and γ-amino butyric acid (GABA), are known to play a role in both epilepsy and depression.

The Relationship of Epilepsy Syndromes to Depression
There has been considerable debate as to the association between any particular epilepsy syndrome and depression. People with lesional temporal lobe epilepsy are more likely to have intractable seizures and to be taking more extensive medication than those with non-temporal lobe epilepsy. Therefore, they may be at an increased risk of developing depression. Thus, some studies have shown patients with temporal lobe epilepsy to be more prone to depression than other groups, but other investigations have failed to confirm this observation.