Sodium valproate
Encyclopedia
Sodium valproate or valproate sodium (USAN
) is the sodium salt of valproic acid
and is an anticonvulsant
used in the treatment of epilepsy
, anorexia nervosa
, panic attack
, anxiety disorder
, posttraumatic stress disorder, migraine
and bipolar disorder
, as well as other psychiatric conditions requiring the administration of a mood stabilizer
. Sodium valproate can be used to control acute episodes of mania
and acute stress reaction
. Side effects can include tiredness, tremors, nausea, vomiting and sedation. The intravenous
formulations are used when oral administration is not possible.
In pregnancy, valproate has the highest risk of birth defects of any of the commonly-used antiepilepsy drugs. However, some epilepsy can only be controlled by valproate, and seizures also pose grave risk to mother and child.
Some of the common adverse effects include: tiredness, tremor, sedation and gastrointestinal disturbances. In addition, about 10% of the users experience reversible hair loss.
All antiepileptic medications have been shown to be associated with higher risks of fetal abnormalities (mostly for spina bifida
) since at least 1983 with the risks being related to the strength of medication used and use of more than one drug
Valproate has also been recognised as sometimes causing a specific facial
changes ("facial phenotype
") termed "fetal valproate syndrome". Sodium valproate has been associated with the rare condition paroxysmal tonic upgaze of childhood, also known as Ouvrier-Billson syndrome, from childhood or fetal exposure (this condition resolved after discontinuing valproate therapy.
While developmental delay is usually associated with altered physical characteristics (dysmorphic feature
s), this is not always the case.
A 2005 study found rates of autism among children exposed to sodium valproate before birth in the cohort studied were 8.9%. The normal incidence for autism in the general population is estimated at less than one percent. It has been suggested that Valproate may best be avoided in women with localisation epilepsy, where there are more effective and less risky alternatives such as carbamazepine
. A 2008 study also suggested a correlation between higher rates of autism in children whose mothers were treated for seizure disorders during pregnancy using sodium valproate (less than 1% for children who didn't receive the drug in vitro vs. 6.3% for children who did). However, only 632 children were followed in this study, prompting criticism that this study was too small to rely on to say whether there was a definitive correlation between the use of sodium valproate in pregnant mothers and higher autism rates in their children, or whether other anti-seizure medications used during pregnancy don't cause this effect.
One multi-centre trial in the UK and US looked at cognitive function in 309 children born to mothers with epilepsy and found that sodium valproate-use was associated with an IQ level eight points lower in children born to mothers taking sodium valproate than mothers taking other anti-epileptic drugs. The authors of the study attempted to correct for confounding factors, but this is an observational study, and therefore cannot prove a causal link. It should be noted, however, that to prove a causal link requires a randomised-controlled trial, which is not possible to perform. It is therefore unlikely that any stronger evidence will become available.
A class action
is currently underway in the United Kingdom
regarding the claim that the drug used in pregnancy caused a range of problems in children, including autism
, learning and social difficulties, ADHD, spinal stenosis
, facial abnormalities, vision defects, dyslexia
, dyspraxia
, delayed speech and motor development.
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...
) is the sodium salt of valproic acid
Valproic acid
Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...
and is an anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
used in the treatment of epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
, anorexia nervosa
Anorexia nervosa
Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...
, panic attack
Panic attack
Panic attacks are periods of intense fear or apprehension that are of sudden onset and of relatively brief duration. Panic attacks usually begin abruptly, reach a peak within 10 minutes, and subside over the next several hours...
, anxiety disorder
Anxiety disorder
Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
, posttraumatic stress disorder, migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
and bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
, as well as other psychiatric conditions requiring the administration of a mood stabilizer
Mood stabilizer
A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, typically bipolar disorder.-Uses:...
. Sodium valproate can be used to control acute episodes of mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...
and acute stress reaction
Acute stress reaction
Acute stress reaction is a psychological condition arising in response to a terrifying or traumatic event...
. Side effects can include tiredness, tremors, nausea, vomiting and sedation. The intravenous
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
formulations are used when oral administration is not possible.
In pregnancy, valproate has the highest risk of birth defects of any of the commonly-used antiepilepsy drugs. However, some epilepsy can only be controlled by valproate, and seizures also pose grave risk to mother and child.
Some of the common adverse effects include: tiredness, tremor, sedation and gastrointestinal disturbances. In addition, about 10% of the users experience reversible hair loss.
U.S.
- Intravenous injection – Depacon by Abbott LaboratoriesAbbott LaboratoriesAbbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
. - Syrup – Depakene by Abbott LaboratoriesAbbott LaboratoriesAbbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
. (Note Depakene capsules are valproic acid). - Depakote tablets are a mixture of sodium valproate and valproic acid.
Australia
- Epilim Crushable Tablets Sanofi-AventisSanofi-AventisSanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
- Epilim Sugar Free Liquid Sanofi-AventisSanofi-AventisSanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
- Epilim Syrup Sanofi-AventisSanofi-AventisSanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
- Epilim Tablets Sanofi-AventisSanofi-AventisSanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
- Sodium Valproate Sandoz Tablets Sanofi-AventisSanofi-AventisSanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
- Valpro Tablets AlphapharmAlphapharmAlphapharm is a generic drug manufacturing company based in Australia. Alphapharm manufactures many different generic pharmaceutical medicines. It is an owned by Mylan Pharmaceuticals . Alphapharm's logo is a green circle with a white lowercase alpha enclosed. Alphapharm is the greatest sole...
- Valproate Winthrop Tablets Sanofi-AventisSanofi-AventisSanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
UK
- Tablets – Orlept by Wockhardt and Epilim by Sanofi-AventisSanofi-AventisSanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
. - Oral solution – Orlept Sugar Free by Wockhardt and Epilim by Sanofi-Aventis.
- Syrup – Epilim by Sanofi-Aventis.
- Intravenous injection – Epilim Intravenous by Sanofi-Aventis.
- Extended release tablets – Epilim Chrono by Sanofi-Aventis. A combination of sodium valproate and valproic acid in a 2.3:1 ratio.
- Enteric-coated tablets – Epilim EC200 by Sanofi-synthélabo. A 200 mg sodium valproate enteric-coatedEnteric coatingAn enteric coating is a barrier applied to oral medication that controls the location in the digestive system, where it is absorbed. Enteric refers to the small intestine, therefore enteric coatings prevent release of medication before it reaches the small intestine.Most enteric coatings work by...
tablet.
UK only
- Capsules – Episenta prolonged release by Beacon.
- Sachets – Episenta prolonged release by Beacon.
- Intravenous solution for injection – Episenta solution for injection by Beacon.
Germany, Switzerland, Norway, Finland
- Tablets – Orfiril by Desitin Pharmaceuticals
- Intravenous injection – Orfiril IV by Desitin Pharmaceuticals
South Africa
- Syrup – Convulex by Byk Madaus
- Tablets – Epilim by sanofi~synthelabo
Canada
- Intravenous injection – Epival or Epiject by Abbott LaboratoriesAbbott LaboratoriesAbbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
. - Syrup – Depakene by Abbott LaboratoriesAbbott LaboratoriesAbbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
. Generic formulations include Apo-Valproic and ratio-Valproic.
Japan
- Tablets – Depakene by Kyowa Hakko KirinKyowa Hakko Kirinis a Japanese pharmaceutical company, among the 50 largest in the world by revenue. The company is a member of the Nikkei 225.-External links:*...
. - Extended release tablets – Depakene-R by Kyowa Hakko Kogyo and Selenica-R by KowaKowaKōwa was a Japanese era name of the Southern Court during the Era of Northern and Southern Courts after Tenju and before Genchū. This period spanned the years from February 1381 to April 1384. The Southern Court emperors in Yoshino during this time-frame were and...
. - Syrup – Depakene by Kyowa Hakko Kogyo.
Europe
In much of Europe, Depakine and Depakine Chrono (tablets) are equivalent to Epilim and Epilim Chrono above.Taiwan
- Tablets (white round tablet) – Depakine by Sanofi Winthrop IndustrieSanofi-AventisSanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
(France).
Safety in pregnancy
The risk of birth defects with valproate is two to five times higher than other frequently-used anti-epileptic drugs (absolute rates of birth defects 6-11%). Children born to mothers using valproate have significantly lower I.Q. scores (9 points). However, some epilepsy can only be controlled by valproate, and seizures during pregnancy can have grave consequences for both mother and child. Doctors recommend that women who intend to become pregnant should be switched to a different drug using combined therapy if possible, which takes several months. Women who are already pregnant and taking a high dose of valproate should try to lower their dose.All antiepileptic medications have been shown to be associated with higher risks of fetal abnormalities (mostly for spina bifida
Spina bifida
Spina bifida is a developmental congenital disorder caused by the incomplete closing of the embryonic neural tube. Some vertebrae overlying the spinal cord are not fully formed and remain unfused and open. If the opening is large enough, this allows a portion of the spinal cord to protrude through...
) since at least 1983 with the risks being related to the strength of medication used and use of more than one drug
Valproate has also been recognised as sometimes causing a specific facial
Face
The face is a central sense organ complex, for those animals that have one, normally on the ventral surface of the head, and can, depending on the definition in the human case, include the hair, forehead, eyebrow, eyelashes, eyes, nose, ears, cheeks, mouth, lips, philtrum, temple, teeth, skin, and...
changes ("facial phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
") termed "fetal valproate syndrome". Sodium valproate has been associated with the rare condition paroxysmal tonic upgaze of childhood, also known as Ouvrier-Billson syndrome, from childhood or fetal exposure (this condition resolved after discontinuing valproate therapy.
While developmental delay is usually associated with altered physical characteristics (dysmorphic feature
Dysmorphic feature
Dysmorphic feature is a medical term referring to a difference of body structure that is suggestive of a congenital disorder, genetic syndrome, or birth defect. A dysmorphic feature can be a minor and isolated birth defect...
s), this is not always the case.
A 2005 study found rates of autism among children exposed to sodium valproate before birth in the cohort studied were 8.9%. The normal incidence for autism in the general population is estimated at less than one percent. It has been suggested that Valproate may best be avoided in women with localisation epilepsy, where there are more effective and less risky alternatives such as carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
. A 2008 study also suggested a correlation between higher rates of autism in children whose mothers were treated for seizure disorders during pregnancy using sodium valproate (less than 1% for children who didn't receive the drug in vitro vs. 6.3% for children who did). However, only 632 children were followed in this study, prompting criticism that this study was too small to rely on to say whether there was a definitive correlation between the use of sodium valproate in pregnant mothers and higher autism rates in their children, or whether other anti-seizure medications used during pregnancy don't cause this effect.
One multi-centre trial in the UK and US looked at cognitive function in 309 children born to mothers with epilepsy and found that sodium valproate-use was associated with an IQ level eight points lower in children born to mothers taking sodium valproate than mothers taking other anti-epileptic drugs. The authors of the study attempted to correct for confounding factors, but this is an observational study, and therefore cannot prove a causal link. It should be noted, however, that to prove a causal link requires a randomised-controlled trial, which is not possible to perform. It is therefore unlikely that any stronger evidence will become available.
A class action
Class action
In law, a class action, a class suit, or a representative action is a form of lawsuit in which a large group of people collectively bring a claim to court and/or in which a class of defendants is being sued...
is currently underway in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
regarding the claim that the drug used in pregnancy caused a range of problems in children, including autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
, learning and social difficulties, ADHD, spinal stenosis
Spinal stenosis
Lumbar spinal stenosis is a medical condition in which the spinal canal narrows and compresses the spinal cord and nerves at the level of the lumbar vertebra. This is usually due to the common occurrence of spinal degeneration that occurs with aging. It can also sometimes be caused by spinal disc...
, facial abnormalities, vision defects, dyslexia
Dyslexia
Dyslexia is a very broad term defining a learning disability that impairs a person's fluency or comprehension accuracy in being able to read, and which can manifest itself as a difficulty with phonological awareness, phonological decoding, orthographic coding, auditory short-term memory, or rapid...
, dyspraxia
Dyspraxia
Developmental dyspraxia is a motor learning difficulty that can affect planning of movements and co-ordination as a result of brain messages not being accurately transmitted to the body...
, delayed speech and motor development.