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Depression in Epilepsy – Mechanisms and Therapeutic Approaches
The Relationship of Epilepsy Syndromes to Depression
Table 1: Psychotropic Properties of Antiepileptic Drugs
There has been considerable debate as to the association between any
particular epilepsy syndrome and depression. People with lesional
Antiepileptic Drug Negative Positive
temporal lobe epilepsy are more likely to have intractable seizures and to
Barbiturates Depression, hyperactivity Anxiolytic, hypnotic
be taking more extensive medication than those with non-temporal lobe
Carbamazepine Irritability Mood-stabilising,
Oxcarbazepine antimanic
epilepsy. Therefore, they may be at an increased risk of developing
Ethosuximide Behavioural abnormalities, –
depression. Thus, some studies have shown patients with temporal lobe
psychosis
epilepsy to be more prone to depression than other groups, but other
Felbamate Depression, anxiety, Increased attention
investigations have failed to confirm this observation. irritability and concentration
Gabapentin Behavioural problems Anxiolytic
Examining the relationship between depression and type of temporal
in children
lobe epilepsy, Quiske et al.
16
found that patients with temporal lobe
Lamotrigine Insomnia, agitation Mood-stabilising,
antidepressant
epilepsy and mesial temporal sclerosis were more likely to report
Levetiracetam Irritability, emotional lability Antimanic?
symptoms of depression than patients with neocortical temporal lobe
Phenytoin Encephalopathy Antimanic?
pathology. In general terms, it seems that patients with complex
Pregabalin ? Anxiolytic
partial seizures are more likely to have a depressive disorder.
17
With Tiagabine Depression (non-convulsive Antianxiety?
regards to the temporal lobe association with depression, it is of status epilepticus)
interest that there are a number of studies outside the field of epilepsy
Topiramate Depression, psychomotor Mood-stabilising
in the psychiatric literature that suggest an association between
slowing, psychosis
Valproate Encephalopathy Mood-stabilising,
hippocampal volume loss and affective disturbances.
18,19
Thus,
antimanic, anxiolytic
although further research in this area is needed, neuroimaging studies
Vigabatrin Depression, aggression, –
are revealing an underlying brain network of depression in psychiatric
psychosis
patients without a neurological disorder, in keeping with the findings
Zonisamide Agitation, depression, Antimanic?
in patients with epilepsy. psychosis
There are studies linking frontal lobe dysfunction to depression in epilepsy.
The latter have emerged from investigations using brain imaging (positron vigabatrin. As in psychiatric practice it is known that benzodiazepines and
emission tomography [PET] or single-photon emission computed other GABA agonists are clinically associated with depression, and that
tomography [SPECT]) and neuropsychological batteries. Hermann et al.
20
abnormalities of cerebrospinal fluid GABA have been reported in patients
noted that patients with temporal lobe epilepsy and depression were more with depression,
26
the link between sudden cessation of seizures,
likely to perform poorly on frontal lobe neuropsychological tasks, GABAergic agents and the onset of depression seems reasonably secure.
especially with a left-sided seizure focus. Schmitz et al.
21
noted similar Furthermore, these studies have revealed that patients with epilepsy and
frontal changes and localisations using SPECT, and, using PET, Bromfield a prior history of an affective disorder are more likely to develop
et al.
22
reported that patients with temporal lobe epilepsy and associated depression in these circumstances.
depression revealed bilateral reductions of frontal lobe metabolism, a
phenomenon also called ‘hypo-frontality’. Although these studies were on Treatment Strategies for Depression in Epilepsy
a limited number of patients, concordance between the findings supports It is important to state that there has been only one controlled trial of
an anatomical association between temporal lobe epilepsy, depression the effects of an intervention for mood disorders in epilepsy, and the
and frontal lobe dysfunction. evidence for treatment strategies relies heavily on clinical experience.
Psychiatric symptoms that are temporally related to the occurrence of
The Relationship of Antiepileptic Drugs and Depression seizures do not need any specific psychotropic treatment, and a better
The association between barbiturates and depression is well-known, but control of seizures is often the most effective solution.
more recent data suggest that it is possible to distinguish between
antiepileptic drugs (AEDs) with the potential to have positive effects on In the case of a mood disorder characterised by symptoms occurring
mood, such as carbamazepine and valproic acid, and others likely to have independently of seizures, psychopharmacotherapy may be required,
detrimental effects (see Table 1). but evidence in favour of a particular drug is lacking. The only
published controlled trial involved nomifensine, an antidepressant that
The role of AEDs in precipitating depression is of considerable interest is no longer available.
27
Selective serotonin re-uptake inhibitors (SSRIs)
following the introduction of a spectrum of compounds referred to as have become the first-line drug treatment for primary major
‘new AEDs’.
2
Within the literature, the concept of forced normalisation depression and dysthymic disorder in psychiatric practice. However,
has been revived. This phenomenon describes the sudden switching off studies about efficacy and safety in epilepsy are lacking. During recent
of seizures in people with long-lasting epilepsy, followed by the years, a number of authors have approached the clinical problem of
development of an alternative psychiatric syndrome. Very often this is a treating mood disorders in epilepsy from different points of view.
28–30
psychotic disorder, but affective symptoms have been also reported.
23–25
A few open studies have been published about the efficacy of
sertraline,
31,32
citalopram,
33–35
reboxetine,
34
mirtazapine
34
and
The AEDs most often associated with the occurrence of depressive fluoxetine.
32
The study by Thomè-Souza et al.
32
is of particular interest
symptoms seem to be those that act at the benzodiazepine-GABA because it is the only published paper involving children and
receptor complex, and include barbiturates, tiagabine, topiramate and adolescents with epilepsy and depression.
EUROPEAN NEUROLOGICAL DISEASE 2007 59
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