Influence of common drugs on the EEG and on seizure threshold

Anti-Depressants

Tricyclic anti-depressants such as imipramine, amitriptyline, doxepin, desipramine, and nortriptyline usually increase the amount of beta activity, as well as theta activity in the record. The frequency of the PDR is usually decreased. Paroxysmal slow waves or even spikes may be seen. In patients with epilepsy, seizure frequency could be increased. With high doses, seizures have been reported in patients without a history of epilepsy. Acute intoxication may produce widespread poorly reactive alpha-range activity and spikes. Absence status can be seen with tricyclic anti-depressants.

Of the newer anti-depressants, bupropion stands out as lowering the seizure threshold with a rate of seizures of about 1.5%. There are no definite effects on the EEG of the newer anti-depressants.

Of note, selective serotonin reuptake inhibitors (SSRI) and other anti-depressants can cause serotonin syndrome with mental status changes, autonomic instability, myoclonus, and tremor. The EEG in serotonin syndrome can show diffuse slowing, spikes, and generalized periodic discharges with a triphasic morphology.

With the exception of trazodone, nearly all anti-depressants have been noted to decrease REM sleep with variable effects on stage I, II, and slow wave sleep.

Anti-Epileptic Drugs

Phenytoin, unlike barbiturates and benzodiazepines, does not produce prominent beta activity. Rather, it tends to cause an increase in the degree of diffuse slow waves in the theta range. With chronic use there is usually a decline in the frequency of the PDR. At toxic levels, diffuse irregular delta activity may be recorded along with paroxysmal rhythmic delta activity.

Carbamazepine and oxcarbazepine usually have little effect on the EEG at therapeutic levels. An increase in diffuse slowing may occur. Epileptiform activity is usually not materially altered, although an increase in focal spikes has been reported. Rarely, generalized epileptiform potentials develop. Vigabatrin is also associated with the development of generalized epileptiform potentials occasionally with absence of myoclonic seizures.

Valproic acid at therapeutic levels produces little or no change in the EEG background. Its principal effect is a reduction in generalized epileptiform discharges, particularly 3 Hz generalized spike and wave discharges. At toxic levels, valproate may produce an encephalopathy characterized by lethargy with a recording dominated by diffuse delta waves.

Lamotrigine decreases the frequency of interictal spikes and sharp waves and is not associated with either increased beta activity or increased slowing. Lamotrigine can worsen (or ameliorate) myoclonic seizures. Levetiracetam decreases interictal epileptiform potentials typically without other effects on the EEG. Ethosuximide decreases generalized spike and wave and absence seizures.

As of this writing, there are a multitude of other AEDs whose effect on the EEG is either minor and/or not fully investigated.

Anti-Microbial Agents

β -lactam antibiotics, specifically penicillin, the cephalosporins and the carbapenems, are well known to be pro-convulsant, causing an altered mental status, jerks, generalized seizures and even status epilepticus. The β -lactam ring can bind to the GABA receptor making GABA a less effective inhibitory neurotransmitter. For all of these agents, risk factors in the development of seizures include high doses, renal failure, and meningitis. Of all of these agents, imipenum, a carbapenem, is the worst culprit, causing seizures in approximately one third of patients with meningitis. The EEG with β -lactam induced encephalopathy is usually slow with generalized epileptiform potentials, at times with a triphasic morphology. Isoniazid and the flouroquinolones are also known to lower the seizure threshold.

Barbiturates

Barbiturates produce an increase in the amount and amplitude of beta activity. The beta may reach high amplitudes and, although diffuse, is often most prominent in the frontal regions. As the blood level of the barbiturate rises, slower activity begins to invade the recording along with slowing of the PDR. Barbiturate intoxication leads to changes similar to those associated with general anesthesia. Diffuse, unreactive delta activity may be recorded, while beta activity disappears. Later stages lead to burst-suppression and ultimately an isopotential or flat record. Abrupt withdrawal after long-term treatment may lead to asynchronous slowing along with generalized epileptiform activity.