Depressive disorder is a frequent comorbid psychiatric condition in patients with epilepsy. It is more common in patients with temporal lobe epilepsy and frontal lobe seizures. Research has revealed a strong correlation between these two conditions. The early recognition of depressive symptoms in an epileptic patient is a predictor to improve quality of life. Besides treating epilepsy, antiepileptics have a role in treating nonepileptic conditions like mood disorders and pain syndromes. However, it is to be considered that certain antiepileptics decrease seizure threshold and increase seizure frequency.
Over the years, a significant amount of research has been conducted showing relationship between epilepsy and depression. Epilepsy and depression are common conditions and often they occur together. Approximately, 40-60% people with epilepsy are affected with depressive symptoms . This is a review article highlighting a strong association between two entities. The main idea behind this review article is to encourage practitioners to keep a close eye on symptoms of depression in people with epilepsy and to treat them accordingly which can impact positively on their quality of life.
what is epilepsy? It is important to understand epilepsy on individual basis before moving on further. Epilepsy or a “seizure disorder” is a neurological condition affecting people of all ages. It involves a spectrum of various kinds of seizures, each presenting in a unique way in person to person. The two terms Epilepsy and seizure are used interchangeably; however, these are different in a context of frequency of occurrence as seizure is a single occurrence and epilepsy is two or more unprovoked seizures. According to Epilepsy foundation there are about 3.4 million people in United states who have epilepsy and there are 150,000 of new cases of epilepsy in the United States each year. It is also evident from a systemic review and meta-analysis research by A. K Ngugi, et al that median incidence of epilepsy as almost twice as high in low income countries than of high
income countries . The cause of epilepsy could be familial or could be secondary to stroke, brain infection, traumatic brain injury or idiopathic. Diagnosis requires a multidisciplinary approach including clinical presentation along with EEG, CT scan head, MRI, Neuropsychological testing, blood work. There are some seizures which present with normal finding on EEG. These are called pseudo-seizures and require a detail evaluation by a psychiatrist.
Epilepsy tend to impact a person on physical and psychological grounds as the occurrence of seizure is often uncertain. This could lead to an increase risk of mood disorders, physical trauma, cognitive issues, behavioral disturbances, depression, hospitalizations and mortality . It is evident from a survey in UK that people with epilepsy tend to suffer from anxiety and sleep disorders more than the people without epilepsy . This sleep disturbances and anxiety can significantly affect the quality of life in a negative way predisposing a person to develop depression.
As the focus of medicine has transitioned to research, we are now able to uncover that depression and epilepsy often coexist together. It is approximated that life time prevalence of depression in correlation with epilepsy is about 55% . The exact cause of this association is still debatable as various mechanisms explain this link. People with depression have sleep deprivation which can decrease seizure threshold and increase seizure frequency. Preictal psychiatric symptoms usually
consists of a constellation of symptoms preceding seizure and
can last from minutes to days including prodromal symptom of
depressed mood and irritability which is relieved after the onset
of seizure or in some cases after few days of seizure activity .
Inter Ictal depression or dysphoria consist of brief episodes of
crying spells, feeling of worthlessness, anhedonia, helplessness,
hopelessness which usually last less than 30sec. In addition,
inter ictal depression is also manifested by agitation, psychotic
disturbances and impulse control issues which can ultimately
predispose to increased suicidal tendencies [5,7]. It is important
to recognize all these phases as their prompt recognition and
their immediate treatment can lead to prevention of a seizure
activity and would also improve quality of life.
It is stated that Depression affects some parts of limbic
system of brain which includes amygdala which is a center
for emotional/stress responses and hippocampus which has a
role in cognition. This results in reduced hippocampal volume
and functional or physical alteration of amygdala. Research
publication have demonstrated increased risk of depression in
patients with temporal epilepsy .
This is supported by the temporal lobe epilepsy refractory
to antiepileptic medications that could lead to hippocampal
sclerosis . Studies have shown some correlation showing that
people who have hippocampal sclerosis had a history of febrile
convulsant seizure in childhood. Also, there is a study on infants
with complex febrile seizures validating that sometimes complex
prolonged febrile seizures can lead to acute hippocampal
injury which later evolves to hippocampal atrophy . This
phenomenon could also explain an association between epilepsy
and depressive symptoms secondary to reduced hippocampal
Antiepileptics also have a significant role in various
psychiatric disorders where they are primarily used for mood
stabilization and for treating anxiety. However, effects of
antiepileptics in terms of their therapeutic benefits and side
effect profile varies from person to person. It is important
to consider that studies performed on one group of people
on AEDs should not be implied to another group. This is even
more of significance in patients with epilepsy where there
is a considerable variation in response to these drugs based
on different reactions. Research has shown that people with
epilepsy on antiepileptics are more predisposed to increased
risk of depression as compared to the other populations .
According to Siddhartha, certain antiepileptics are notorious
for this behavior which includes levetiracetam, ethosuximide,
phenytoin, topiramate etc., which may precipitate underlying
depression or anxiety. However, it is interesting to note that some
AEDs like lamotrigine have beneficial effects of antidepressants
[10,11]. It is stated in publications that each of AEDs act through
unique mechanisms which alters the electrochemical gradient
resulting in positive or negative behavioral changes. These
mechanisms include GABAergic modulation either through
stimulating chloride channels or inhibiting GABA uptake and
inhibition of voltage gated sodium channels . Landolt
hypothesis of forced normalization should also be taken into
consideration regarding behavioral manifestation of AEDs which
states possibility of depressive symptoms after diminution of
epilepsy either through surgery or use of AEDs .
There is evidence suggesting that tricyclic antidepressants
and MAOI have a dose- dependent potential to decrease seizure
threshold. Bupropion has also shown to decrease seizure
threshold at all doses. Now there are cases reported in which
Bupropion has led to seizure activity even at its extended release
formulation. Alternatively, second generation antidepressants
SSRI like sertraline, paroxetine, escitalopram does not lower
seizure threshold and can be safely used for treating depression
in epileptic patient [13,14]. There could also be a strong
connection among depression, epilepsy and suicide as a people
with MDD harm themselves by over ingesting antidepressants
which could be lethal causing seizures or on the other hand, a
people with epilepsy can become depressed over time with their
illness and try to commit suicide.
In the light of above review article, it is concluded that
epilepsy and depression share a unique bidirectional relationship
as depression is a most frequent comorbidity in patients with
epilepsy. Given their strong correlation a clinician should use a
holistic approach to identify depressive symptoms in epileptic
patients. There is also a need to investigate about any history
of seizure disorder as there is evidence suggesting hippocampal
changes in these patients predisposing to depression in later
life. It is imperative for practitioners to obtain a through drug
history, monitor their drug levels and to make correct choice
of antidepressants if treating epilepsy. This also necessitates a
need of collaboration between a neurologist and a psychiatrist
to manage these conditions.