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Antiepileptic drugs and sleep?

Studies of anticonvulsant medications show an increase in sleep stability with anticonvulsant drugs, but it is hard to distinguish between the effects of these drugs on seizures and effects on sleep independent of this (as we know that seizures profoundly disrupt sleep). More recently, studies that carefully look at this, some by testing drugs in normal volunteers who do not have epilepsy, have clearly shown that anticonvulsants can either enhance or disrupt sleep independent of their effects on seizures.

Benzodiazepines (such as diazepam and lorazepam) and barbiturates( phenobarbital, primidone ) are used less commonly for chronic treatment of seizure disorders, but have the most convincing evidence for detrimental effects on sleep. Both of these classes of medications have been used as sleep promoting agents, although newer drugs have replaced these in recent years. They do decrease the time to fall asleep, but also decrease the amount of REM sleep and (in the case of benzodiazepines) slow wave sleep. Therefore, sleep quality can be adversely affected. The studies on the effects of other anticonvulsant drugs show somewhat variable results, but a few conclusions can be made. Phenytoin may increase light sleep and decrease sleep efficiency, and studies show decreased REM sleep. Findings for carbamazepine are more variable, but there also seems to be a reduction in sleep particularly with initial treatment.

Studies of newer AEDs suggest fewer detrimental effects on sleep. One study with lamotrigine showed decreases in slow wave sleep, but others have shown no change. Gabapentin has no detrimental effects on sleep, and in fact seems to enhance slow wave sleep in patients with epilepsy and in normal volunteers. Gabapentin also increases sleep continuity and decreases awakenings. Furthermore, limited studies suggest that gabapentin may be useful in the treatment of one common sleep disorder, restless legs syndrome, although carbamazepine and lamotrigine have also been used. Levetiracetam seems to have no detrimental effects on sleep. The effects of zonisamide, oxcarbazepine, and topiramate on sleep and sleep disorders are not known.

Overall, patients with sleep problems may need to adjust their anticonvulsant dosing or, rarely, change to another drug (see Table 1). Other conditions can sometimes contribute to sleep disruption in patients with epilepsy; these are described in more detail below but effects of AEDs are listed in Table 2.

Table 1: Summary of AED effects on sleep

AED Sleep latency Sleep efficiency Stage 1 SWS REM Daytime drowsiness
barbiturates + NE NE NE - -
benzodiazepines + NE NE - - -
carbamazepine NE NE NE NE - -
phenytoin + NE - NE - -
valproic acid NE NE - NE NE -
felbamate ? ? ? ? ? -
gabapentin NE NE NE + +/NE ?
lamotrigine NE NE NE - +/NE ?
levetiracetam ? ? NE NE + ?
tiagabine NE + NE + NE ?
topiramate ? ? ? ? ? ?
zonisamide ? ? ? ? ? ?

+: improves; -: worsen; NE: no effect; ?: unknown
note that some of these results represent small studies, and the effect may not occur in all patients

Table 2: Use of AEDs in sleep disorders and comorbid conditions which can effect sleep

Condition Potentially useful AED(s) Potentially harmful AED(s)
Insomnia barbiturates, benzodiazepines, gabapentin, tiagabine felbamate
Restless legs/PLMS gabapentin, carbamazepine, benzodiazepines  
Obstructive sleep apnea   benzodiazepines, barbiturates
Depression lamotrigine  
Anxiety benzodiazepines  
Migraine valproic acid, gabapentin, topiramate  
Neuropathic pain carbamazepine, gabapentin, lamotrigine, topiramate  

PLMS: periodic limb movements of sleep

Topic Editor: Carl Bazil, M.D.
Last Reviewed:10/01/05


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