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Questions and Answers
Valproate is primarily metabolized in the kidneys.
Valproate is primarily metabolized in the kidneys.
False
Drugs that lower the seizure threshold can enhance the anticonvulsant effect of valproate.
Drugs that lower the seizure threshold can enhance the anticonvulsant effect of valproate.
False
Loading doses of valproate are not generally well tolerated.
Loading doses of valproate are not generally well tolerated.
False
The plasma levels of olanzapine can be significantly increased by the concurrent use of valproate.
The plasma levels of olanzapine can be significantly increased by the concurrent use of valproate.
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Weight should be monitored as part of the pre-valproate workup.
Weight should be monitored as part of the pre-valproate workup.
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Full Blood Count (FBC) and Liver Function Tests (LFTs) should be repeated every 6 months when on valproate.
Full Blood Count (FBC) and Liver Function Tests (LFTs) should be repeated every 6 months when on valproate.
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A small study suggests that abruptly discontinuing valproate has no negative effects on bipolar disorder.
A small study suggests that abruptly discontinuing valproate has no negative effects on bipolar disorder.
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Valproate is considered safe for use in women of childbearing age when treating bipolar disorder.
Valproate is considered safe for use in women of childbearing age when treating bipolar disorder.
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The Medicines and Healthcare products Regulatory Agency (MHRA) advises against initiating valproate in women of childbearing age without specialist advice.
The Medicines and Healthcare products Regulatory Agency (MHRA) advises against initiating valproate in women of childbearing age without specialist advice.
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Valproate has no known cognitive impairment risks for children exposed to it in utero.
Valproate has no known cognitive impairment risks for children exposed to it in utero.
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A minimum dose of 300mg of aspirin is required to inhibit the metabolism of valproate.
A minimum dose of 300mg of aspirin is required to inhibit the metabolism of valproate.
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Valproate should not be prescribed to women under 30 years of age.
Valproate should not be prescribed to women under 30 years of age.
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The teratogenic potential of valproate is well understood by most women of childbearing age.
The teratogenic potential of valproate is well understood by most women of childbearing age.
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Valproate plasma levels above 94 mg/L are consistently associated with a more robust response in acute mania.
Valproate plasma levels above 94 mg/L are consistently associated with a more robust response in acute mania.
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Weight gain is least likely to occur when valproate is taken alone without any other medications.
Weight gain is least likely to occur when valproate is taken alone without any other medications.
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Valproate activates the extracellular signal-regulated kinase (ERK) pathway.
Valproate activates the extracellular signal-regulated kinase (ERK) pathway.
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Valproate's pharmacokinetics are simplified and follow a one-compartment model.
Valproate's pharmacokinetics are simplified and follow a one-compartment model.
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Sodium valproate and semi-sodium valproate are equivalent in dosing.
Sodium valproate and semi-sodium valproate are equivalent in dosing.
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Valproate is a complex molecule with a well-understood mechanism of action.
Valproate is a complex molecule with a well-understood mechanism of action.
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Gastric irritation and hyperammonaemia can occur with doses of valproate above 750 mg/day.
Gastric irritation and hyperammonaemia can occur with doses of valproate above 750 mg/day.
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Children taking multiple antiseizure medications are at lower risk for adverse effects from valproate.
Children taking multiple antiseizure medications are at lower risk for adverse effects from valproate.
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The form of valproate used more commonly in the UK is valproic acid.
The form of valproate used more commonly in the UK is valproic acid.
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There is no evidence supporting the use of valproate in cancer treatments.
There is no evidence supporting the use of valproate in cancer treatments.
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The once-daily Chronoformulation of valproate leads to higher peak plasma levels compared to conventional formulations.
The once-daily Chronoformulation of valproate leads to higher peak plasma levels compared to conventional formulations.
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A full blood count (FBC) is not required as a pre-treatment test before starting valproate.
A full blood count (FBC) is not required as a pre-treatment test before starting valproate.
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Valproate has been shown to have a 50% response rate in treating mania.
Valproate has been shown to have a 50% response rate in treating mania.
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Semi-sodium valproate is primarily used in the US for treating affective disorders.
Semi-sodium valproate is primarily used in the US for treating affective disorders.
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Valproate is primarily eliminated through the liver and rarely causes hepatic failure.
Valproate is primarily eliminated through the liver and rarely causes hepatic failure.
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A large US study indicated that patients treated with semi-sodium valproate had shorter hospital stays than those treated with valproic acid.
A large US study indicated that patients treated with semi-sodium valproate had shorter hospital stays than those treated with valproic acid.
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Valproate is less effective than lithium in treating acute mania in patients who have not responded to lithium.
Valproate is less effective than lithium in treating acute mania in patients who have not responded to lithium.
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The 2020 meta-analysis placed valproate in the top three treatment options for bipolar depression.
The 2020 meta-analysis placed valproate in the top three treatment options for bipolar depression.
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Valproate is generally better tolerated than lithium.
Valproate is generally better tolerated than lithium.
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In the long-term treatment of rapid cycling illness, lithium outperforms valproate.
In the long-term treatment of rapid cycling illness, lithium outperforms valproate.
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Combining valproate with aripiprazole is shown to have poorer outcomes than valproate alone.
Combining valproate with aripiprazole is shown to have poorer outcomes than valproate alone.
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Valproate has been used to treat aggressive behaviors of variable etiology.
Valproate has been used to treat aggressive behaviors of variable etiology.
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There is substantial evidence supporting the efficacy of valproate in the prophylaxis of bipolar disorder.
There is substantial evidence supporting the efficacy of valproate in the prophylaxis of bipolar disorder.
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Valproate shows a sustained better response rate compared to olanzapine in patients with rapid cycling illness.
Valproate shows a sustained better response rate compared to olanzapine in patients with rapid cycling illness.
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Open-label studies are considered more rigorous evidence than double-blind, placebo-controlled trials.
Open-label studies are considered more rigorous evidence than double-blind, placebo-controlled trials.
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The National Institute for Health and Clinical Excellence (NICE) recommends valproate for use in women of child-bearing potential.
The National Institute for Health and Clinical Excellence (NICE) recommends valproate for use in women of child-bearing potential.
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Study Notes
Valproate
- Valproate is a simple branched-chain fatty acid
- Valproate inhibits the metabolism of y-aminobutyric acid (GABA), reducing the turnover of arachidonic acid
- Valproate activates the extracellular signal-regulated kinase (ERK) pathway and thus alters synaptic plasticity, interferes with intracellular signaling promotes BDNF expression
- Valproate alters the expression of multiple genes involved in transcription regulation, cytoskeletal modifications, and inositol depletion
- Valproate has indirect effects on non-GABA pathways
- Valproate is hepatically metabolised; drugs that inhibit CYP enzymes can increase valproate levels (e.g., erythromycin, fluoxetine and cimetidine)
- Valproate can increase the plasma levels of some drugs by inhibiting glucuronidation
- Valproate may also significantly lower plasma concentrations of some drugs
- The mechanism of the anticonvulsant effect of valproate is unknown
- Weight gain is a possible side effect
- Valproate can cause both gastric irritation and hyperammonemia
- Valproate is an established human teratogen, therefore alternative antiseizure medications are preferred in women of childbearing age
- Women who have mania are likely to be sexually disinhibited when unwell
- The risk of unplanned pregnancy is likely to above population norms(where 50% of pregnancies are unplanned).
- Valproate is highly protein bound and can be displaced by other protein-bound drugs such as aspirin
- Other less strongly protein bound drugs, such as warfarin, can be displaced by valproate, leading to higher free levels and toxicity
- Valproate is available in three forms: sodium valproate, valproic acid (licensed for the treatment of epilepsy) and semi-sodium valproate (licensed for the treatment of acute mania).
- Both semi-sodium and sodium valproate are metabolised to valproic acid, which is responsible for the pharmacological activity of all three preparations
- In the US, valproic acid is widely used in the treatment of bipolar illness, and in the UK sodium valproate is widely used.
- The doses of sodium valproate and semi-sodium valproate are not equivalent; a slightly higher (approximately 10%) dose is required if sodium valproate is used to allow for the extra sodium content
- It is unclear if there is any difference in efficacy between valproic acid, valproate, and semi-sodium valproate. A large US quasi-experimental study found that inpatients who initially received the semi-sodium preparation had a hospital stay that was a third longer than patients who initially received valproic acid.
- Valproate controlled release (Epilim Chrono) can be administered as a once daily dose, whereas other sodium and semi-sodium valproate preparations require at least twice daily administration
- Randomised controlled trials (RCTs) have shown valproate to be effective in the treatment of mania, with a response rate of 50%
Pre-valproate workup
- FBC and LFTs. Baseline measure of weight is desirable
Prescribing
- Titrate dose upwards against response and side effects. Loading doses can be used and are generally well tolerated.
- Note that CR sodium valproate (Epilim Chrono) can be given once daily. All other formulations must be administered at least twice daily
- monitor plasma levels to assure adequate dosing and treatment compliance
Monitoring
- FBC and LFTs if clinically indicated
- Weight (or BMI)
Stopping
- Reduce slowly over at least 1 month
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Description
This quiz covers essential clinical considerations regarding the use of valproate, particularly in the context of bipolar disorder and its interactions with other medications. Participants will learn about dosage recommendations, safety profiles, monitoring requirements, and specific precautions for women of childbearing age. It aims to enhance understanding of valproate's therapeutic implications and risks associated with its use.
