Primidone, sold under various brand names (including Mysoline), is a barbiturate medication that is used to treat partial and generalized seizures[7] and essential tremors.

[7] Its common side effects include sleepiness, poor coordination, nausea, and loss of appetite.

[9] Primidone is an anticonvulsant of the barbiturate class;[7] however, its long-term effect in raising the seizure threshold is likely due to its active metabolite, phenobarbital.

Other pharmacological agents include alprazolam, clonazepam, atenolol, sotalol, nadolol, clozapine, nimodipine, and botulinum toxin A.

[22] In 1965, Monroe and Wise reported using primidone along with a phenothiazine derivative antipsychotic and chlordiazepoxide in treatment-resistant psychosis.

[23] What is known is that 10 years later, Monroe went on to publish the results of a meta-analysis of two controlled clinical trials on people displaying out-of-character and situationally inappropriate aggression, who had abnormal EEG readings, and who responded poorly to antipsychotics; one of the studies was specifically mentioned as involving psychosis patients.

[25] Primidone can cause drowsiness, listlessness, ataxia, visual disturbances, nystagmus, headache, and dizziness.

[29] Dupuytren's contracture is almost exclusively found in Caucasians, especially those of Viking descent, and highest rates are reported in northern Scotland, Norway, Iceland, and Australia.

It has also been associated with alcoholism, heavy smoking, diabetes mellitus, physical trauma (either penetrating in nature or due to manual labor), tuberculosis, and HIV.

In 1981, phenobarbital, one of primidone's metabolites, was shown to only induced a significant porphyrin level at high concentrations in vitro.

Likewise, postmenopausal women taking anticonvulsants have a greater risk of fracture than their drug-naive counterparts.

[26] Granulocytopenia, agranulocytosis, red-cell hypoplasia and aplasia, and megaloblastic anemia are rarely associated with the use of primidone.

[36] Megaloblastic anemia is actually a group of related disorders with different causes that share morphological characteristics—enlarged red blood cells with abnormally high nuclear-cytoplasmic ratios resulting from delayed maturation of nuclei combined with normal maturation of cytoplasm, into abnormal megakaryocytes and sometimes hypersegmented neutrophils; regardless of etiology, all of the megaloblastic anemias involve impaired DNA replication.

[9] Epileptic women are generally advised to take folic acid,[40] but there is conflicting evidence regarding the effectiveness of vitamin supplementation in the prevention of such defects.

[9][41] Additionally, a coagulation defect resembling vitamin K deficiency has been observed in newborns of mothers taking primidone.

[43] Schaffer et al. 1999 reported that one of their treatment failures, a 45-year-old woman taking 50 mg a day along with lithium 600 mg/day, clozapine 12.5 mg/day, trazodone 50 mg/day, and alprazolam 4 mg/day for three and a half months experienced auditory hallucinations that led to discontinuation of primidone.

This syndrome consists of fever, rash, peripheral leukocytosis, lymphadenopathy, and occasionally hepatic necrosis.

[48] Hyperammonemic encephalopathy was reported by Katano Hiroyuki of the Nagoya City Higashi General Hospital in early 2002 in a patient who had been stable on primidone monotherapy for five years before undergoing surgery for astrocytoma, a type of brain tumor.

[49] A randomized, controlled trial w found that primidone was more likely to cause impotence than phenytoin, carbamazepine, or phenobarbital.

[26] The most common symptoms of primidone overdose are coma with loss of deep tendon reflexes, and during the recovery period, if the patient survives, disorientation, dysarthria, nystagmus, and ataxia,[51] lethargy, somnolence, vomiting, nausea, and occasionally, focal neurological deficits which lessen over time.

[59] Primidone and the other enzyme-inducing anticonvulsants can cut the half-life of antipyrine roughly in half (6.2 ± 1.9 h vs. 11.2 ± 4.2 h), and increases the clearance rate by almost 70%.

[66] It also interferes with the metabolism of dexamethasone, a synthetic steroid hormone, to the point where its withdrawal from the regimen of a 14-year-old living in the United Kingdom made her hypercortisolemic.

[67] Tempelhoff and colleagues at the Washington University School of Medicine's Department of Anesthesiology reported in 1990 that primidone and other anticonvulsant drugs increase the amount of fentanyl needed during craniotomy based on the patient's heart rate.

[69] It is believed to work via interactions with voltage-gated sodium channels that inhibit high-frequency repetitive firing of action potentials.

[71] The major metabolite, phenobarbital, is also a potent anticonvulsant in its own right and likely contributes to primidone's effects in many forms of epilepsy.

[77] Primidone, carbamazepine, phenobarbital, and phenytoin are among the most potent hepatic enzyme-inducing drugs in existence, which occurs at therapeutic doses.

[51] Primidone is a congener of phenobarbital, where the carbonyl oxygen of the urea moiety is replaced by two hydrogen atoms.

[86] It was brought to market a year later by the Imperial Chemical Industry, now known as AstraZeneca in the United Kingdom[56][87] and Germany.

[95] Primidone was seen by some as too valuable to withhold based on the slight possibility of this rare side effect[90] and by others as dangerous enough to be withheld unless phenobarbital or some other barbiturate failed to work for this and other reasons (i.e., reports of permanent psychosis).

[97] It is marketed as several different brands, including Mysoline (Canada,[98] Ireland,[99] Japan,[100] the United Kingdom,[101] the United States[98] and Turkey[102]), Prysoline (Israel, Rekah Pharmaceutical Products, Ltd.),[103] Apo-Primidone,[97][104] Liskantin (Germany, Desitin),[105] Resimatil (Germany, Sanofi-Synthélabo GmbH),[106] Mylepsinum (Germany, AWD.pharma GmbH & Co., KG).,[107] and Sertan (Hungary, 250 mg tablets, ICN Pharmaceuticals Inc.[1]) Primidone has veterinary uses, including the prevention of aggressive behavior and cannibalism in gilt pigs, and treatment of nervous disorders in dogs and other animals.