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.
In terms of tremor amplitude reduction, it is just as effective as propranolol, reducing it by 50%. Both drugs are well studied for this condition, unlike other therapies, and are recommended for initial treatment. 250 mg/day (low-dose therapy) is just as good as 750 mg/day (high-dose therapy).Primidone is not the only anticonvulsant used for essential tremor; the others include topiramate and gabapentin. Other pharmacological agents include alprazolam, clonazepam, atenolol, sotalol, nadolol, clozapine, nimodipine, and botulinum toxin A. Many of these drugs were less effective (according to Table 1), but a few were not. Only propranolol has been compared to primidone in a clinical trial. Psychiatric disorders
In 1965, Monroe and Wise reported using primidone along with a phenothiazine derivative antipsychotic and chlordiazepoxide in treatment-resistant psychosis. What is known is that ten 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. When they were given various anticonvulsants not only did their EEGs improve, but so did the aggression.In March 1993, S.G. Hayes of the University of Southern California School of Medicine reported that nine out of twenty-seven people (33%) with either treatment-resistant depression or treatment-resistant bipolar disorder had a permanent positive response to primidone. A plurality of subjects were also given methylphenobarbital in addition to or instead of primidone.