What is the use of Primidone (anticonvulsant medication)?

From the Guidelines

Primidone should not be used as a first-line treatment for simple febrile seizures due to its potential toxicities outweighing the relatively minor risks associated with the condition. According to the American Academy of Pediatrics practice guideline 1, continuous anticonvulsant therapy with phenobarbital, primidone, or valproic acid and intermittent therapy with diazepam are effective in reducing febrile-seizure recurrence, but the potential toxicities associated with these agents outweigh the relatively minor risks associated with simple febrile seizures.

Some key points to consider when using primidone include:

• The typical starting dose for adults is 125-250 mg daily, gradually increasing to an effective maintenance dose of 750-1500 mg daily divided into 3-4 doses.
• Common side effects include drowsiness, dizziness, fatigue, and nausea, which often improve with continued use.
• Primidone is metabolized in the body to phenobarbital, which contributes to its therapeutic effect but also its sedative properties.
• Patients should be aware that primidone may interact with other medications, particularly oral contraceptives, anticoagulants, and other anticonvulsants.
• Abrupt discontinuation should be avoided as it may precipitate seizures; dosage should be reduced gradually under medical supervision.

It's also important to note that the WHO recommendations 1 suggest that antiepileptic drugs should not be routinely prescribed to adults and children after a first unprovoked seizure, and that discontinuation of antiepileptic drug treatment should be considered after 2 seizure-free years. Additionally, the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO) practice guideline update 1 recommends that anticonvulsant medications are not effective as primary seizure prophylaxis in patients with newly diagnosed brain tumors, and that prophylactic anticonvulsants should not be used routinely in these patients.

In terms of specific patient populations, the WHO recommendations 1 suggest that women with epilepsy should have seizures controlled as well as possible with antiepileptic drug monotherapy at minimum effective dose, and that valproic acid should be avoided if possible. The SNO and EANO practice guideline update 1 also notes that some AEDs, such as valproate, have been suggested to have anti-tumor activity, but that the use of these agents should be individualized based on the specific patient population and clinical context.

Overall, while primidone can be an effective treatment for certain types of seizures, its use should be carefully considered and individualized based on the specific patient population and clinical context, taking into account the potential risks and benefits of treatment.

From the FDA Drug Label

Primidone, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. Primidone tablets are prescription medicine used alone or with other medicines to treat people with: generalized tonic-clonic (grand mal) seizures complex partial (psychomotor) seizures partial (focal) epileptic seizures The main use of primidone is to control grand mal, psychomotor, and focal epileptic seizures. It is used alone or with other anticonvulsants to treat people with:

• Generalized tonic-clonic (grand mal) seizures
• Complex partial (psychomotor) seizures
• Partial (focal) epileptic seizures 2, 2

From the Research

Mechanisms of Action

• Primidone exerts its therapeutic effects by blocking voltage-gated sodium channels and by modulating GABA-A and GABA-B intracortical circuits 3
• The exact mechanisms underlying the efficacy of primidone in essential tremor are not fully elucidated, but it has been shown to decrease corticospinal excitability, prolong the cortical silent period, increase long interval intracortical inhibition, increase short afferent inhibition, and decrease short interval intracortical inhibition 3

Efficacy in Essential Tremor

• Primidone has been shown to be effective in reducing the amplitude of essential tremor in both untreated and propranolol-treated patients 4
• Low doses of primidone were found to be as effective as high doses in reducing tremor 4
• Primidone decreased tremor more than propranolol in some studies 4, 5
• A double-blind, placebo-controlled trial found primidone to be significantly superior to placebo in reducing the magnitude of hand tremor, with efficacy comparable to that of propranolol 5

Side Effects and Tolerability

• Acute reactions to the initial dose and side effects of higher doses of primidone can cause drug intolerance 4
• An acute toxic reaction to an initial small dose of primidone was seen in six of 22 patients in one study 5
• Primidone has been found to cause more intolerable acute toxic effects, such as nausea, vomiting, dizziness, and sedation, compared to other antiepileptic drugs 6
• Decreased libido and impotence were more common in patients given primidone compared to other antiepileptic drugs 6