Valproate semisodium (Depakote)

How does it work?

Depakote tablets contain the active ingredient valproate semisodium, which is is a type of medicine called a mood stabiliser. It is used to treat psychiatric illness known as bipolar affective disorder, or manic depression.

(NB. Valproate semisodium is another form of the antiepileptic medicine, sodium valproate. Sodium valproate is also used as a mood stabiliser, but most brands are unlicensed for this purpose. Valproate semisodium is a form of sodium valproate that is licensed for use as a mood stabiliser. Both can be known simply as valproate.)

People with bipolar affective disorder suffer from abnormal mood swings, which range from episodes of abnormally high mood (mania or hypomania) to episodes of abnormally low mood (depression). Valproate semisodium works as a mood stabiliser by increasing the amount of a natural nerve calming chemical in the brain called GABA.

The brain and nerves are made up of thousands of nerve cells that communicate with each other through electrical signals. These signals must be carefully regulated for the brain and nerves to function properly. When abnormally rapid and repetitive electrical signals are released in the brain, it becomes over-stimulated and normal function is disturbed.

The nerve activity is normally kept in balance by a natural chemical in the brain called GABA. When GABA is released in the brain it acts as a natural calming agent. Once GABA is broken down in the brain, it can no longer act on the nerves. When only small amounts of GABA are present, the brain may become 'overexcited'.

Valproate semisodium prevents the breakdown of GABA in the brain. This enables more GABA to be available to calm nerve cells for a longer period of time. By calming the nerve cells, valproate semisodium prevents excessively rapid and repetitive firing of electrical signals. This stabilises the electrical nerve activity in the brain and is thought to explain how valproate semisodium calms periods of mania.

In addition to treating manic episodes, valproate semisodium is prescribed by specialists as a maintenance treatment to help stabilise mood and prevent episodes of ill health.

What is it used for?

  • Treatment of manic episodes of bipolar affective disorder (manic depression).
  • As a mood stabiliser in bipolar affective disorder to help prevent episodes of mania in people whose manic episode responded to this medicine.


  • Depakote tablets should be swallowed whole with a drink of water and not broken, crushed or chewed.
  • This medicine may cause drowsiness. If affected do not drive or operate machinery.
  • This medicine can cause some people to put on weight. Talk to your doctor about this before you start treatment so that you can discuss strategies, such as diet and exercise, for minimising any weight gain.
  • This medicine may on rare occasions affect your liver, pancreas or blood cells. You should have blood tests to monitor your liver function, blood cells and blood clotting time before you start treatment. Your liver function should be monitored for the first six months of treatment, and your blood cell count should be checked before any surgery. Tell your doctor immediately if you experience any of the following symptoms during treatment, particularly if they come on suddenly or occur in the first six months of taking the medicine: lack of appetite and energy, weakness, feeling generally unwell, drowsiness, nausea, vomiting, severe abdominal pain, swelling of ankles, yellowing of the skin or whites of the eyes (jaundice), or unusual bruising or bleeding.
  • There may be a small increased risk of suicidal thoughts and behaviour in people taking antiepileptic medicines such as valproate for any condition. For this reason, it is very important to seek medical advice if you, or someone else taking this medicine, experience any changes in mood, distressing thoughts, or feelings about suicide or self-harm at any point while taking this medicine. For more information speak to your doctor or pharmacist.
  • This medicine may cause skin reactions. You should let your doctor know if you develop a rash, skin peeling, itching, or other unexplained skin reaction while taking this medicine.
  • Long-term treatment with valproate may decrease bone mineral density, which could increase the risk of breaking a bone. Your doctor might want you to take vitamin D supplements to avoid this if you are going to be immobilised for a long time, or if you don't get enough sunlight or calcium in your diet.
  • People with diabetes should be aware that valproate semisodium can cause false positive results in urine tests for ketones.
  • You should not suddenly stop taking this medicine unless your doctor tells you otherwise, as suddenly stopping treatment could make your symptoms return. When this medicine is stopped, it should normally be done gradually, under the supervision of your specialist.

Use with caution in

  • Decreased kidney function.
  • History of liver disease.
  • Disorders of urea production in the liver (urea cycle disorders).
  • Long-term inflammation of skin and some internal organs (systemic lupus erythematosus).
  • Diabetes.

Not to be used in

  • Active liver disease.
  • Personal or family history of severe liver problems, particularly if due to a medicine.
  • Hereditary blood disorders called porphyrias.
  • Depakote is not recommended for children and adolescents under 18 years of age, as its safety and effectiveness for treating mania have not been studied in this age group.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy. If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

  • Pregnant women taking valproate have a higher risk of carrying a baby with developmental problems and malformations. In view of this it is vital that women with bipolar disorder receive specialist psychiatric advice before starting treatment with valproate, so they are well informed of potential risks and benefits of treatment.
  • Valproate should not be used for bipolar disorder in women who are pregnant, unless your doctor considers it essential because other treatments are ineffective or not tolerated.
  • Women who decide to try for a baby while taking valproate should start taking folic acid 5mg daily as soon as contraception is stopped, as this may reduce risk of neural tube defects such as spina bifida in the baby.
  • Women who decide to continue taking valproate during a pregnancy should be prescribed valproate on its own, in the lowest effective dose, in doses that are split over the day, and if possible as a prolonged release brand. These measures can help minimise the risk to the baby. Specialist medical advice must be sought.
  • Valproate passes into breast milk in small amounts, but there have been no reports of harmful effects from this on nursing infants. Breastfeeding is considered acceptable for women taking this medicine. Seek further medical advice from your doctor.

Label warnings

  • This medication is to be swallowed whole, not chewed.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

  • Disturbances of the gut such as diarrhoea, nausea, vomiting or abdominal pain.
  • Increased appetite and weight gain.
  • Decrease in the number of platelets in the blood (thrombocytopenia).
  • Temporary hair loss -– regrowth may be curly.
  • Increased alertness.
  • Aggression.
  • Hyperactivity.
  • Shaky movements and unsteady walk (ataxia).
  • Tremor.
  • Inflammation of blood vessels (vasculitis).
  • Drowsiness.
  • Confusion.
  • Liver disorders.
  • Irregular or stopping of menstrual periods.
  • Skin rashes.
  • Decreased numbers of white blood cells in the blood (leucopenia).
  • Anaemia.
  • Acne.
  • Increased hair growth (hirsutism).
  • Inflammation of the pancreas (pancreatitis).

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer. For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.

Valproate semisodium may increase the blood levels of the following medicines. As this could increase the risk of their side effects, your doctor may need to reduce the dose of these medicines if you taken them in combination with valproate:

  • benzodiazepines such as lorazepam
  • bupropion
  • lamotrigine (valproate may also increase the risk of skin reactions associated with lamotrigine)
  • phenobarbital
  • phenytoin (phenytoin blood levels should be monitored if taken with valproate)
  • primidone
  • tricyclic antidepressants such as amitriptyline and nortriptyline
  • zidovudine.

There may be an increased risk of side effects on the liver if sodium valproate is taken with phenytoin or carbamazepine.

There may be an increased chance of side effects such as dizziness, tiredness, blurred vision and vomiting if valproate is taken with carbamazepine.

There may be increased drowsiness and sedation if valproate is taken with benzodiazepines, eg diazepam.

The following medicines may increase the blood level of valproate:

  • cimetidine
  • felbamate
  • large repeated doses of aspirin.

The following medicines may decrease the blood level of valproate semisodium:

  • carbapenem antibiotics, eg imipenem
  • carbamazepine
  • phenytoin
  • phenobarbital
  • primidone.

Colestyramine may reduce the absorption of valproate from the gut. This can be minimised by separating doses of these medicines by at least three hours.

There may be an increased risk of a drop in white blood cell count if olanzapine is taken with valproate. If you are taking olanzapine in combination with this medicine it is important to tell your doctor if you experience any of the following symptoms: sore throat, mouth ulcers, high temperature (fever), or general illness or infection. Your doctor may want to take a blood test to check your blood cells.

Other medicines containing the same active ingredient

There are currently no other medicines available in the UK that contain valproate semisodium as the active ingredient.