Managing psychiatric illness in patients with epilepsy

• absence of confusion or autonomic dysfunction
• presence of more organized thinking
• absence of EEG changes.³³

Alteration of an AED regimen can induce post-ictal psychosis. Iatrogenic psychosis sometimes is observed after right-sided temporal lobe surgery.³⁴

Interictal psychoses probably occur as a result of aberrant nerve regeneration, with an increased concentration of dopa­mine in the brain after long-term seizure control. Epileptic psychosis is distin­guished from schizophrenia by the pre­dominance of visual hallucinations, no alteration of personality or affect, and glial proliferation.35 Some patients exhibit “forced normalization,” in which psy­chotic features appear after epilepsy has been treated successfully and EEG find­ings are normalized.³⁶

Management of psychosis in epilepsy includes ensuring the patient’s safety, rul­ing out medical causes of psychosis, and preventing relapse. Prescribe antipsychotics with caution because many of these agents have epileptogenic potential or can inter­fere with the hepatic metabolism of AEDs. Quetiapine, risperidone, and haloperi­dol have low potential for seizure induc­tion; chlorpromazine and clozapine are more likely to precipitate an ictal event.³⁷ Ziprasidone, quetiapine, and aripiprazole often are prescribed for post-ictal and inter-ictal psychoses.³⁸

Sleep disorders
Epilepsy patients often complain about dif­ficulty sleeping, namely:

• 10% to 33% exhibit restless leg syndrome or periodic limb movement disorder
• 10% to 65% have obstructive sleep apnea
• 11% to 28% report excessive daytime sleepiness.³

Convulsive activity and the rate of gen­eralization of partial seizures are increased by sleep, especially non-rapid eye move­ment sleep. Rapid eye movement (REM) sleep suppresses ictal activity, but the pat­tern of REM sleep is disrupted in epilepsy. Seizures and some sleep disorders present with similar symptoms, such as confusion and amnesia (Table 2).39

Management of comorbid sleep prob­lems includes:

• effective control of seizures
• avoidance of polypharmacy
• assuring sleep hygiene.

Disordered sleep resulting from an AED might be relieved by switching to another medication.39

Substance abuse
Abuse of substances is a significant risk factor for recurrence of seizures.

Alcohol, at a low dose, has antiepileptic properties; intoxication rarely induces a seizure, although seizures often accom­pany alcohol withdrawal.⁴⁰

Acute alcohol abuse increases the free level of AEDs by inhibiting 1) microsomal enzyme systems and 2) binding of albumin by metabolites, such as acetaldehyde. These effects can lead to the dangerous outcome of respiratory depression, especially with drugs like phenobarbital.

Chronic alcohol use induces hepatic enzymes, which augments clearance of AEDs, except benzodiazepines. Metabolism of AEDs is decreased because of reduced hepatic blood flow.

Moderate drinking does not increase the incidence of seizures in medication-adherent patients. People who have recur­rent alcohol-withdrawal seizures do not have a heightened risk of epilepsy.41

Cannabis. Animal studies have docu­mented the anticonvulsant effect of Cannabis in partial and generalized epi­lepsy and a proconvulsant effect in absence (petit mal) seizures.⁴²

Tramadol, caffeine. Patients who abuse tramadol or who have an excessive intake of caffeine have a decreased seizure threshold.⁴³

Opiates can exert a proconvulsant or anti­convulsant action, depending on the type of endorphin receptors involved.⁴⁴

Cocaine decreases the seizure threshold by 1) blocking cerebral GABA receptors and 2) inhibiting dopamine reuptake, thus elevating excitatory neurotransmitters. Cocaine can cause a generalized or focal seizure; the latter is caused by intracere­bral stroke or hemorrhage.45

The AEDs topiramate and lamotrigine tend to decrease the desire to abuse alcohol by enhancing inhibitory control by way of decreasing dopamine activity in the meso­corticolimbic system.⁴⁶

Memory deficits
The relative risk of dementia among epi­lepsy patients is greater compared with the general population. Recurrent seizures can result in cognitive deficits; epilepsy has been documented in 2% to 64% of Alzheimer’s disease patients.⁴⁷

Progressive amnesia, with an associated decline in cognition in epilepsy patients despite AED therapy, warrants a dementia workup.⁴⁸ Patients with an ictal disorder often have difficulty with memory, espe­cially if the hippocampus is affected, such as in temporal lobe epilepsy. Seizures are a common manifestation of several neu­rodegenerative conditions, and may be associated with a treatable dementia or psychosis in patients with cyanocobalamin deficiency.⁴⁹

Several memory deficits are associated with seizure disorders:

• Transient epileptic amnesia can be ictal or post-ictal, or can be a manifestation of an underlying seizure disorder. The con­dition is associated with isolated memory deficits; other cognitive functions usually are intact.
• Accelerated long-term memory deficit occurs when patients forget skills acquired over the past few days or weeks. The problem can be reduced with sleep.⁵⁰
• Remote memory impairment is characterized by inability to recall personal information from the past.⁵¹

When considering a diagnosis of a mem­ory deficit as a manifestation of dementia, keep in mind that cognitive impairment also can develop after epilepsy treat­ment—although most newer medications cause relatively few such problems.^52,53

2-pronged management. It is difficult to establish a temporal association between epilepsy and dementia. When the condi­tions coexist, appropriate treatment of both is important, because inadequate control of seizures can heighten release of amyloid toxins in the hippocampus. This results in rapidly progressive cognitive decline.⁵⁴