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 (5-100 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 1000 patients drug patients with events per 1000 patients relative risk: incidence of events in drug patients/ incidence in placebo patients risk difference: additional drug patients with events per 1000 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 primidone or any other aed must balance the risk of suicidal thoughts or 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. usage in pregnancy to provide information regarding the effects of in utero exposure to primidone, physicians are advised to recommend that pregnant patients taking primidone enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. information on the registry can also be found at the website http://www.aedpregnancyregistry.org/. the effects of primidone in human pregnancy and nursing infants are unknown. recent 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 diphenylhydantoin 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. 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 methodologic problems in obtaining adequate data on drug teratogenicity in humans; the possibility also exists that other factors leading to birth defects, e.g. , genetic factors or the epileptic condition itself, may be more important than drug therapy. 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 disorders 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. neonatal hemorrhage, with a coagulation defect resembling vitamin k deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. pregnant women under anticonvulsant therapy should receive prophylactic vitamin k 1 therapy for one month prior to, and during, delivery.

determinations of primidone may be necessary for optimal dosage adjustment. the clinically effective serum level for primidone is between 5 to 12 µg/ml. in patients already receiving other anticonvulsants primidone should be started at 100 to 125 mg at bedtime and gradually increased to maintenance level as the other drug is gradually decreased. this regimen should be continued until satisfactory dosage level is achieved for the combination, or the other medication is completely withdrawn. when therapy with primidone alone is the objective, the transition from concomitant therapy should not be completed in less than two weeks. pediatric dosage for children under 8 years of age, the following regimen may be used: days 1 to 3: 50 mg at bedtime. days 4 to 6: 50 mg b.i.d. days 7 to 9: 100 mg b.i.d. day 10 to maintenance: 125 mg t.i.d. to 250 mg t.i.d. for children under 8 years of age, the usual maintenance dosage is 125 to 250 mg three times daily or, 10 to 25 mg/kg/day in divided doses.