Introduction
Valproic acid, also known as valproate, is a drug for the treatment of epilepsy, also known as seizure disorders. Accordingly, it belongs to the group of drugs known as antiepileptic drugs. It is a very potent drug, but its mechanism of action has not yet been fully explained.
Why can valproic acid cause side effects?
Valproic acid probably attacks the neurotransmitter system in the brain by amplifying inhibitory signals. As with all medicines, side effects can occur when taking valproic acid, some of which are common, while others have been shown to occur only occasionally or very rarely in studies.
Possible side effects of valproic acid
Very often: Frequently: Occasionally: Rarely: Very rarely: Observed in individual cases:
- Thrombocytopenia (reduction of blood platelets)
- Leukopenia (reduction of white blood cells)
- Clinically not relevant increases of ammonia in serum
- Weight gain or loss
- Reduced or increased appetite
- Drowsiness and dizziness
- Trembling, sensory disturbances such as tingling or numbness of the skin
- Temporary hair loss
- Bleeding, headache, confusion
- Tensions, insecure gait, excessive activity
- Stupor (a physical numbness while awake)
- Organic brain disease, which can regress after weaning
- Diarrhea and excessive salivation,
- Severe, sometimes fatal liver dysfunction (children are at increased risk),
- Oedema (water retention in the tissue)
- Lupus erythematosus and vasculitis (immune reactions of the body)
- Renal dysfunction
- Disturbance of brain function including mental performance
- Irregular menstruation
- Cystic enlarged ovaries
- Disturbance of the bone marrow function
- Severe anaemia
- Hyponatremia (lowered sodium concentration in the blood)
- Damage to the pancreas with partially fatal outcome
- Hypersensitivity reactions,
- Eosinophilia
- Pleural effusion
- Sensory delusions, brain disorders, movement disorders
- Noise in the ear, temporary or permanent hearing loss
- Reduction of bone density (osteoporosis)
- Bedwetting in children
- Drop in body temperature
Possible side effects of taking valproic acid include increased appetite and resulting weight gain. Some studies report weight gain in between 20 and 70% of patients treated with the antiepileptic. There are many possible causes for the side effect of the therapy: Whether patients are affected by this side effect is influenced by many factors: weight gain leads to discontinuation of therapy with valproic acid in many patients, and overweight also increases the risk of metabolic syndrome and diabetes mellitus.
When introducing therapy with valproic acid, patients should be informed about the possible side effects and keep an eye on their body weight. Physical activity and a balanced diet can prevent weight gain. However, if the body weight increases significantly, a change in therapy to another anti-epileptic drug should be considered.
- A disorder of the so-called neuroendocrine regulatory system (i.e. a hormonal disorder)
- Insulin resistance induced by valproic acid, which increases blood sugar
- A reduced breakdown of fatty acids in the blood, which leads to the new synthesis of fat storage
- Reduced physical activity
- Weight gain resulting from excessive calorie intake due to these factors
- Gender (women are more often affected than men)
- Life phase (puberty as a critical time)
- Duration and dose of the treatment
- Initial weight
- Genetic predisposition
Valproic acid can have various side effects on the skin. A possible but rare side effect of valproic acid is skin rashes. The risk is relatively low in monotherapy, but increases especially in combination therapy with the antiepileptic drug lamotrigine.Although an allergic reaction is suspected, the mechanism behind the development of skin rashes is not fully explained.
The rash can affect smaller areas, but also the whole body. In addition, skin elevations such as pustules or wheals can occur, as well as itching. A rare side effect of valproate therapy is also the occurrence of lupus erythematosus, an immune disease.
This is accompanied by butterfly-shaped and scaly skin rashes, especially on the hands. Itching usually occurs as a side effect of rashes associated with valproate therapy. If skin reactions such as redness, rash or itching occur, a doctor should be consulted immediately.
If necessary, a doctor can stop treatment with valproic acid and prescribe an alternative anti-epileptic drug. Headaches may occasionally occur when taking valproic acid. Interestingly, the drug is used off-label but also for migraine prophylaxis or prevention of cluster headaches, which shows that headaches do not have to occur in every user.
If, in addition to headaches, other neurological symptoms such as dizziness, gait insecurity, visual disturbances, behavioral disorders or even delusions occur, a doctor should definitely be consulted. In the most severe cases, taking valproate can lead to a so-called encephalopathy (brain disease), which can manifest itself acutely or chronically. Dizziness is a non-specific symptom and occurs as a frequent side effect of valproic acid therapy.
Dizziness can often be prevented by slowly rising from a sitting or lying position, but if the dizziness persists for a long time and severely restricts everyday life, a doctor should be consulted. Another possible side effect of valproic acid therapy is visual disturbances, such as double vision. A nystagmus visible from the outside (a rapid eye twitch) can also occur.
These side effects can occur with practically all antiepileptic drugs and can affect the ability to drive and operate machines. In case of visual disturbances, the treating neurologist should be consulted. Tremor, medically known as tremor, often occurs as a side effect when taking valproic acid.
It can be an isolated symptom and does not necessarily require discontinuation of the medication, but tremor can also be an indication of valproate-induced acute or chronic encephalopathy. Other concomitant symptoms may reinforce the suspicion of encephalopathy: Acute valproate encephalopathy requires discontinuation of therapy and, like chronic valproate encephalopathy, usually recedes completely afterwards. If these or other neurological side effects occur, the patient should always consult a physician.
- Concentration disorders
- Disorientation, slowing down
- Incontinence
- Asterixis (a twitching fall of the stretched arms)
Temporary hair loss is another common side effect of valproic acid. This is known as diffuse hair loss, and therefore affects the entire head. A loss of axillary or pubic hair is less frequent.
The hair loss manifests itself at the earliest four days to two weeks after the beginning of the intake. However, the hair loss is only temporary, after about one to three months after the end of treatment, the hair grows back again. Sensitivities are medically called paraesthesias and can occur as frequent side effects of valproic acid.
The sensation is unpleasant to painful and patients describe various symptoms: The occurrence and intensity of the sensation is dose-dependent, i.e. it increases with an increased intake of the medication. If the sensation is unpleasant and painful, the neurologist treating the patient should be consulted.
- Tingling, numbness
- Falling asleep limbs
- Sensations of heat or cold without adequate stimuli
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