Primidone, sold under various brand names (including Mysoline), is a barbiturate medication that is used to treat partial and generalized seizures and essential tremors. It is taken by mouth. Its common side effects include sleepiness, poor coordination, nausea, and loss of appetite. Severe side effects may include suicide and psychosis. Use during pregnancy may result in harm to the fetus. Primidone is an anticonvulsant of the barbiturate class; however, its long-term effect in raising the seizure threshold is likely due to its active metabolite, phenobarbital. The drug’s other active metabolite is Phenylethylmalonamide (PEMA). Primidone was approved for medical use in the United States in 1954. It is available as a generic medication. In 2023, it was the 239th most commonly prescribed medication in the United States, with more than 1 million prescriptions.
Medical uses
Epilepsy It is licensed for generalized tonic-clonic and complex partial seizures in the United Kingdom. In the United States, primidone is approved for adjunctive (in combination with other drugs) and monotherapy (by itself) use in generalized tonic-clonic seizures, simple partial seizures, complex partial seizures, and myoclonic seizures. In juvenile myoclonic epilepsy, it is a second-line therapy, reserved for when the valproates or lamotrigine do not work and when the other second-line therapy, acetazolamide, does not work. The usual dose for seizure disorder is titrated from 100–125 mg/day up to a maintenance dose of 750-1,500 mg/day (maximum daily dosage is 2 g). Open-label case series have suggested that primidone is effective in the treatment of epilepsy. Primidone has been compared to phenytoin, phenobarbital, mephobarbital, ethotoin, metharbital, and mephenytoin. In adult comparison trials, primidone has been found to be just as effective.
Essential tremor Primidone is not indicated for essential tremor but is often used as a first-line therapy for essential tremor, as is propranolol. In 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. A low-dose therapy (50 mg/day) is just as good as a high-dose therapy (750 mg/day). The usual dose range is 120 to 250 mg/day in two divided doses or as one single dose. 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 than primidone. 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 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. 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 9 out of 27 people (33%) with either treatment-resistant depression or treatment-resistant bipolar disorder had a permanent positive response to primidone. A plurality of subjects was also given methylphenobarbital in addition to or instead of primidone.
Adverse effects
Primidone can cause drowsiness, listlessness, ataxia, visual disturbances, nystagmus, headache, and dizziness. These side effects are the most common, reportedly occurring in more than 1% of users. Transient nausea and vomiting are also common side effects.
… excerpt ends here. Continue reading the full article.
