However, it has been suggested that bone demineralization is most pronounced in young people (25–44 years of age) and one 1987 study of institutionalized people found that the rate of osteomalacia in the ones taking anticonvulsants—one out of nineteen individuals taking an anticonvulsant (vs. none among the thirty-seven people taking none) —was similar to that expected in elderly people. The authors speculated that this was due to improvements in diet, sun exposure and exercise in response to earlier findings, and/or that this was because it was sunnier in London than in the Northern European countries which had earlier reported this effect. In any case, the use of more than one anticonvulsant has been associated with an increased prevalence of bone disease in institutionalized epilepsy patients versus institutionalized people who did not have epilepsy. Likewise, postmenopausal women taking anticonvulsants have a greater risk of fracture than their drug-naive counterparts.Anticonvulsants affect the bones in many ways. They cause hypophosphatemia, hypocalcemia, low Vitamin D levels, and increased parathyroid hormone. Anticonvulsants also contribute to the increased rate of fractures by causing somnolence, ataxia, and tremor which would cause gait disturbance, further increasing the risk of fractures on top of the increase due to seizures and the restrictions on activity placed on epileptic people. Increased fracture rate has also been reported for carbamazepine, valproate and clonazepam. The risk of fractures is higher for people taking enzyme-inducing anticonvulsants than for people taking non-enzyme-inducing anticonvulsants.
This syndrome consists of fever, rash, peripheral leukocytosis, lymphadenopathy, and occasionally hepatic necrosis.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. Additionally, her phenobarbital levels were inexplicably elevated post-surgery. This is much more common with the valproates than with any of the barbiturates. A randomized controlled trial whose results were published in the July 1985 issue of The New England Journal of Medicine found that primidone was more likely to cause impotence than phenytoin, carbamazepine, or phenobarbital. Like phenytoin, primidone is rarely associated with lymphadenopathy. Primidone can also cause vomiting; this happens in 1.0–0.1% of users. Overdose
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, lethargy, somnolence, vomiting, nausea, and occasionally, focal neurological deficits which lessen over time. Complete recovery comes within five to seven days of ingestion. The symptoms of primidone poisoning have generally been attributed to its biotransformation to phenobarbital; however, primidone has toxic effects independent of its metabolites in humans. The massive crystalluria that sometimes occurs sets its symptom profile apart from that of phenobarbital. The crystals are white, needle-like, shimmering, hexagonal plates consisting mainly of primidone.In the Netherlands alone, there were thirty-four cases of suspected primidone poisoning between 1978 and 1982.