al thoughts or behavior in patients taking these drugs for any indication. patients treated with any aed for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different aeds showed that patients randomized to one of the aeds had approximately twice the risk (adjusted relative risk 1.8, 95% ci: 1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. in these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 aed-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. there were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. the increased risk of suicidal thoughts or behavior with aeds was observed as early as one week after starting drug treatment with aeds and persisted for the duration of treatment assessed. because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. the risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. the finding of increased risk with aeds of varying mechanisms of action and across a range of indications suggests that the risk applies to all aeds used for any indication. the risk did not vary substantially by age (5 years to 100 years) in the clinical trials analyzed. table 1 shows absolute and relative risk by indication for all evaluated aeds. table 1: risk by indication for antiepileptic drugs in the pooled analysis indication placebo patients with events per 1,000 patients drug patients with events per 1,000 patients relative risk: incidence of events in drug patients/incidence in placebo patients risk difference: additional drug patients with events per 1,000 patients epilepsy 1.0 3.4 3.5 2.4 psychiatric 5.7 8.5 1.5 2.9 other 1.0 1.8 1.9 0.9 total 2.4 4.3 1.8 1.9 the relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. anyone considering prescribing ethosuximide or any other aed must balance the risk of suicidal thoughts and behavior with the risk of untreated illness. epilepsy and many other illnesses for which aeds are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. patients, their caregivers, and families should be informed that aeds increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. behaviors of concern should be reported immediately to healthcare providers. serious dermatologic reactions serious dermatologic reactions, including stevens-johnson syndrome (sjs), have been reported with ethosuximide treatment. sjs can be fatal. the onset of symptoms is usually within 28 days but can occur later. ethosuximide should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. if signs or symptoms suggest sjs, use of this drug should not be resumed and alternative therapy should be considered. drug reaction with eosinophilia and systemic symptoms (dress) drug reaction with eosinophilia and systemic symptoms (dress), also known as multi organ hypersensitivity, has occurred with ethosuximide. some of these events have been fatal or life-threatening. dress typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. eosinophilia is often present. this disorder is variable in its expression, and other organ systems not noted here may be involved. it is important to note that early manifestations of hypersensitivity (e.g. fever, lymphadenopathy) may be present even though rash is not evident. if such signs or symptoms are present, the patient should be evaluated immediately. ethosuximide should be discontinued if an alternative etiology for the signs or symptoms cannot be established. usage in pregnancy ethosuximide crosses the placenta. reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women. data are more extensive with respect to phenytoin and phenobarbital, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs. cases of birth defects have been reported with ethosuximide. the reports suggesting an elevated incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause and effect relationship. there are intrinsic methodological problems in obtaining adequate data on drug teratogenicity in humans; the possibility also exists that other factors, e.g., genetic factors or the epileptic condition itself, may be more important than drug therapy in leading to birth defects. the great majority of mothers on anticonvulsant medication deliver normal infants. it is important to note that anticonvulsant drugs should not be discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. in individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus. the prescribing physician will wish to weigh these considerations in treating or counseling epileptic women of childbearing potential. ethosuximide is excreted in human breast milk. because the effects of ethosuximide on the nursing infant are unknown, caution should be exercised when ethosuximide is administered to a nursing mother. ethosuximide should be used in nursing mothers only if the benefits clearly outweigh the risks.

psy coexist with absence (petit mal). the optimal dose for most pediatric patients is 20 mg/kg/day.

hese effects may be noted particularly in patients who have previously exhibited psychological abnormalities. there have been rare reports of paranoid psychosis, increased libido, and increased state of depression with overt suicidal intentions. integumentary system: dermatologic manifestations which have occurred with the administration of ethosuximide have included urticaria, pruritic erythematous rashes, stevens-johnson syndrome, and hirsutism. special senses: myopia. genitourinary system: vaginal bleeding, microscopic hematuria.

symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. behaviors of concern should be reported immediately to healthcare providers. prior to initiation of treatment with ethosuximide, the patient should be instructed that a rash may herald a serious medical event and that the patient should report any such occurrence to a physician immediately. patients should be encouraged to enroll in the north american antiepileptic drug (naaed) pregnancy registry if they become pregnant. this registry is collecting information about the safety of antiepileptic drugs during pregnancy. to enroll, patients can call the toll-free number 1-888-233-2334 (see precautions: pregnancy section).