What is being tested?
This test measures the amount of valproate in the blood. Valproate is a drug that is used primarily to treat some types of seizure disorders (also called epilepsy), but is also prescribed to treat bipolar disease and to prevent migraine headaches. It may be prescribed in combination with other antiepileptic drugs such as phenytoin or phenobarb to control certain kinds of seizures.
Seizure disorders affect the brain’s ability to transmit electrical impulses and to regulate nerve activity. During a seizure, a patient may experience changes in consciousness, alterations in sight, smell and taste, and may experience convulsions. Seizures are associated with acute conditions, such as high fevers, head trauma, severe infections and exposure to toxins, and with chronic conditions such as metabolic disorders and brain tumours. In many cases the cause is not known. The frequency of seizures varies from a single episode, to occasional seizures, to recurrent. Rarely, a patient may have a seizure that does not stop without prompt medical intervention. People may experience some fatigue and a short period of confusion after a seizure. Muscle contractions during a seizure can lead to an injury and, in some cases, recurrent seizures can eventually lead to progressive brain damage. For most people there will be little or no residual damage.
Bipolar disorder is a mental condition that is characterised by cycles of depression and mania that may last for days, weeks, months, or years. During a depressive episode those affected may feel sad, hopeless, worthless and have thoughts of suicide. During a manic episode, those affected may be euphoric, irritable, use poor judgment and participate in risky behaviours. Valproate is prescribed to help even out the moods of the person with bipolar disorder, especially mania. It is also given to some patients with recurrent migraine headaches, not so much as to treat migraines but to help prevent their occurrence.
Valproate levels must be maintained within a narrow therapeutic range. Too little and the patient may experience a recurrence of symptoms (seizures, mania or migraines); too much and the patient may experience increased side effects. This balance is not always easily achieved. The drug is metabolised by the liver and is processed at a rate that varies from patient to patient and is affected by a patient’s age and the health of their liver. In addition, valproate levels are often affected by other drugs such as carbamazepine, phenytoin, lamotrigine, and phenobarb. They increase the rate of valproate metabolism, thus decreasing its concentration in the blood.
Dosages of valproate must be adjusted carefully until a steady concentration in the blood is reached. The actual amount of drug that it takes to reach this steady state will vary from person to person and may change over time.
How is it used?
The valproate test is ordered to measure and monitor the amount of valproate in the blood to determine whether drug concentrations are in the therapeutic range. The prescribed dose of the drug may be adjusted up or down depending on the results of the blood test. The test may then be ordered at regular intervals, and as needed, to ensure that therapeutic blood concentrations are maintained. One or more valproate tests may be ordered if a patient starts or stops taking additional medications (to judge their effect, if any, on valproate levels) and may be ordered if the patient has a recurrence of symptoms such as a seizure, a migraine or experiences bipolar mood swings. Doctors will also evaluate their patient for side effects and adverse reactions during initial dosage adjustments and over time. These side effects may include some or a combination of the following:
Very young and elderly patients are more likely to experience increased side effects. In some cases, the severity of side effects may cause the patient and doctor to seek another anti-seizure, bipolar, or migraine medication.
When is it requested?
A valproate level is ordered when a patient begins valproate treatment and when/if a patient’s medications change (other drugs are started, stopped or changed). Once stable blood concentrations in the therapeutic range have been achieved, valproate levels may then be monitored at regular intervals to ensure that it remains within this range.
The test may be ordered when a patient’s condition does not appear to be responding to valproate to determine whether concentrations are too low, the medication is ineffective, and/or to determine if the patient is complying with therapy (taking the valproate regularly). It may also be ordered when a patient experiences a troublesome level of side effects and/or develops complications.
Patients should talk to their doctor about the timing of the sample collection. Since dosage timing varies, and some formulations are time release, collection specifics may vary. Often, the recommended time for sample collection is just before the next dose is taken (trough level). This ensures that the minimum amount of drug to be effective is maintained in the blood.
What does the result mean?
The therapeutic range for valproate has been established at 50 - 120 µg/mL. Within this range, most people will respond to the drug without excessive side effects, however, response varies with each individual. Some people will experience seizures, mood swings or migraines at the low end of the therapeutic range while some people will experience excessive side effects at the upper end. Patients should work closely with their doctor to find the dosage and concentration that works the best for them.
In general, if valproate results are within the therapeutic range, the patient is not having recurrent seizures, mood swings or migraines, and the patient is not experiencing significant side effects, then the dosage of valproate a patient is receiving is considered adequate. Patients should not increase, decrease, or stop taking their medication without consulting with their doctor as it can increase their risk of having a seizure and may affect other medications that they are taking. Dosage determinations and adjustments must be evaluated on a case-by-case basis.
Is there anything else I should know?
Valproate inhibits the metabolism of other seizure medications such as carbamazepine, phenytoin, lamotrigine and phenobarbitone, increasing their concentrations in the blood. If a patient is on additional drugs such as these, they may also need to be monitored with blood tests.
While severe liver injury is rare, mild increases in liver-related enzymes (AST and ALT) occur in up to 20% of those taking valproate; these usually return to normal even if the drug is continued.
The fetus of women who use valproate during pregnancy are at an increased risk of developing several birth defects. Since this drug increases the risk of neural tube defects such as spina bifida, women of child-bearing age who want to become pregnant should talk to their doctors about this subject.
Common questions
Valproate is usually taken every day (sometimes several times a day) for a patient’s lifetime. An exception to this may be patients whose seizures are caused by a temporary condition; they may only need the medication for a short period of time.
It may be taken as a tablet, slow release tablet, a liquid, or sprinkled on a soft food. It is generally taken with food to minimise stomach upset and it is important that the solid forms be swallowed not chewed to avoid mouth and throat irritation.
No, it requires specialised equipment. Blood samples are collected from a vein in the arm and tested in the laboratory.
More information
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