Valproic Acid

Valproic Acid

Valproic acid is an anticonvulsant medication that is primarily used to treat epilepsy, bipolar disorder, neuropathic pain, migraine, attention deficit hyperactivity disorder (ADHD), and other psychological disorders. It exerts its therapeutic effect by affecting certain brain chemicals or neurotransmitters, thus improving overall brain health.

How Valproic Acid Works?

Valproic acid achieves its desired effects through the following important mechanisms:

  1. It increases the levels of gamma-aminobutyric acid (GABA), a neurotransmitter that reduces overstimulation in the brain.
  2. It restores communication between neurons (nerve cells) by reducing overactivity and blocking certain pathways in the brain.
  3. It protects new brain cells by blocking certain enzymes responsible for gene alteration.

Proven Health Benefits of Valproic Acid

Reduces Seizures

Treating seizures is the earliest and most prominent use of this anticonvulsant medication, and it is still prescribed for this condition today. Numerous clinical trials support the safety and efficacy of valproic acid in reducing the prevalence of seizure attacks:

  1. In epileptic children, valproic acid exhibited similar effectiveness to ethosuximide, the current gold standard for treating epileptic seizures.[1]
  2. In patients with glioblastoma multiforme, a deadly brain cancer, valproic acid administration reduced seizure attacks and resulted in a 2-month longer survival.[2]
  3. In late-onset post-stroke epilepsy patients, valproic acid administration was associated with better seizure control.[3]
  4. In patients with chronic seizure, valproic acid was found to be effective at reducing the incidence of attacks.[4]
  5. In patients with idiopathic generalized epilepsies, valproic acid provided superior control of epileptic seizures and was associated with fewer hospitalizations and emergency department visits.[5]
  6. In patients with hemorrhagic stroke (caused by blood vessel rupture), valproic acid reduced the occurrence of seizures in the early period.[6]
  7. In patients with uncontrolled seizures of a generalized or partial type, valproic acid administration was associated with significant reduction in seizure frequency ranging from 25 to 100%.[7]
  8. In patients with poorly controlled complex partial seizures, valproic acid treatment significantly reduced seizure by 50%.[8]
  9. Valproic acid was found to be similar in efficacy with other antiepileptic drugs such as carbamazepine, phenytoin, phenobarbital, and ethosuximide in the treatment of generalized, partial, and absence seizures.[9-10]
  10. In patients with juvenile myoclonic epilepsy, valproic acid significantly reduced the incidence of seizure attacks.[11]
  11. In patients with generalized tonic-clonic seizures, valproic acid administration alone demonstrated greater efficacy at reducing attacks.[12]

Fights Hair Loss

Valproic acid is not just indicated for seizure disorders. Evidence suggests that it can help stimulate hair regeneration and treat the root cause of hair loss:

  1. In male patients with androgenetic alopecia, a type of hair loss common in both genders, valproic acid spray treatment for 24 weeks significantly increased total hair count compared to placebo spray.[13]
  2. In participants with hair baldness, treatment with 7.2% of valproic acid spray on scalp twice a day (morning and evening) for 24 weeks increased linear hair growth rate and final hair density.[14]
  3. In patients with alopecia, administration of valproic acid induced hair growth on bald areas.[15]
  4. A study found that implantation of valproic acid-encapsulated dissolving microneedles stimulated hair follicle regrowth.[16]
  5. A cell study also found that valproic acid has the ability to inhibit glycogen synthase kinase 3ß and activation of Wnt/βcatenin pathway, which in turn induce hair regeneration and hair growth phase (anagen).[17]
  6. In male patients with moderate androgenic alopecia, valproic acid spray treatment for 24 weeks significantly increased total hair count without any adverse side effects.[18]
  7. Treatment of human dermal papilla cells (hair follicles) with valproic acid induced hair regeneration.[19]
  8. Administration of valproic acid in patients with alopecia increased hair count by boosting the production of biotin, a protein that promotes hair growth.[20]

Treats Migraines

There’s also increasing evidence supporting the pain-relieving properties of valproic acid:

  1. In patients with chronic (recurring) migraines, valproic acid administration at daily doses of 500 to 600 mg reduced migraine frequency.[21]
  2. Larger clinical trials confirmed the benefit of valproic acid on migraine attacks and the FDA approved the use of this drug.[22-23]
  3. Valproic acid administration in patients with recurrent migraines was associated with better clinical response.[24]
  4. A study found that low dose of valproic acid (10 mg/kg) for 6 months may be helpful in preventing migraine in pediatric patients.[25]
  5. In patients with severe migraine headache, administration of intravenous valproic acid seems to be safe and rapidly effective at alleviating symptoms.[26]
  6. A study found that valproic acid treats migraine by increasing brain GABA levels.[27]
  7. In adult patients with episodic migraine, valproic acid reduced headache frequency and was reasonably well tolerated.[28]
  8. In patients with refractory migraine, a type of migraine not relieved or prevented by acute migraine therapies, valproic acid administration at a dose of 1,250 mg daily reduced headache severity.[29]
  9. In migraine sufferers, valproic acid administration at a dose of 100–600 mg/day was consistent in alleviating symptoms.[30]
  10. Administration of 400 mg valproic acid twice daily for 8 weeks in patients with migraine was effective in reducing the frequency, severity and duration of the attacks.[31]
  11. Administration of 70 to 120 mg/L of valproic acid in patients with migraine headaches was associated with significantly lesser functional restriction and symptoms.[32]
  12. Valproic acid appeared to be equivalent in efficacy and safety to topiramate, an anti-epileptic drug, in reducing the duration, monthly frequency, and intensity of headache.[33]

Improves Mood

There’s also a good amount of evidence demonstrating the safety and efficacy of valproic acid in stabilizing the mood of patients with various psychological disorders:

  1. In patients with neurosis, a mild mental illness characterized by stress, depression, anxiety, and obsessive behavior, valproic acid significantly improved scores in various tests assessing symptoms such as Clinical Global Impression Scale for panic severity, the Hamilton Psychiatric Rating Scale for Anxiety, and the panic factor of the SCL-90.[34-35]
  2. In patients with panic disorder who failed to respond to conventional treatment, valproic acid reduced symptoms of anxiety and improved low and unstable mood.[36]
  3. In patients with social anxiety disorder, valproic acid administration at 500-2500 mg for 12 weeks improved scores in Liebowitz Social Anxiety Scale (LSAS), a measure of anxiety symptoms.[37]
  4. In patients with generalized anxiety disorder that is resistant to antidepressants, valproic acid improved symptoms by increasing the efficiency of gamma-aminobutyric acid.[38]
  5. In human model of anxiety behavior, valproic acid treatment reduced subjective ratings of anxiety.[39]
  6. In bipolar patients, valproic acid administration at a dose range of 50-300 mg/day for 8 weeks appears to reduce anxiety.[40]
  7. In patients with major depressive disorder, valproic acid significantly improved scores in the Hamilton Rating Scale for Depression (HRSD).[41]
  8. In patients with major depressive disorder who are resistant to antidepressant medications, valproic acid administration provided substantial clinical improvement.[42]
  9. In patients with long-lasting depressive and anxiety symptoms, valproic acid administration at 100–1250 mg/day significantly reduced symptoms.[43-45]
  10. In patients with acute bipolar depression, valproic acid administration significantly reduced symptoms without any adverse effects.[46-50]
  11. In patients with acute mania, a mental illness characterized by great excitement, delusions, and overactivity, valproic acid was similar in efficacy to the antipsychotic drug haloperidol in treating manic episodes.[51]
  12. In patients with schizophrenia, a mental disorder characterized by cognitive impairment and detachment from reality, short-term valproic acid treatment improved psychotic symptoms.[52-55]
  13. In patients with schizoaffective disorder, a mental condition like schizophrenia but with depression and mania symptoms, valproic acid reduced symptoms and was found to be effective than other antipsychotic drugs such as lithium.[56-57]
  14. Valproic acid treatment was also associated with reduced length and intensity of symptoms as well as fewer and shorter hospital stays.[58]

Improves Cognitive Function

Studies also support that valproic acid has positive impact on cognitive health:

  1. In patients with epilepsy, valproic acid treatment was associated with better scores on memory tasks.[59]
  2. In young patients with epilepsy, administration of valproic acid improved attention and memory.[60]
  3. In elderly patients, valproic acid treatment improved attention, concentration, psychomotor speed, and memory.[61]
  4. Valproic acid treatment was also associated with improved attention, memory and visuomotor function among epileptic patients.[62]
  5. In patients with juvenile myoclonic epilepsy, valproic acid improved neuropsychological performance on different cognitive functions such as attention, short-term memory, processing speed, and verbal fluency.[63]
  6. In HIV-infected individuals with cognitive impairment, valproic acid improved mental performance.[64]
  7. In a rat model of convulsive status epilepticus, valproic acid significantly improved spatial cognitive dysfunction.[65]
  8. In rats, valproic acid administration after traumatic brain injury improved cognitive function by protecting brain nerve cells.[66]
  9. In a rat model of Parkinson’s disease, valproic acid prevented death of brain neurons.[67]
  10. Animal and cell studies found that valproic acid may help reverse the progression of Alzheimer’s disease by stimulating growth and development of new neurons.[68-69]
  11. In a rat model of stroke, valproic acid protected against the loss of cognitive function via inhibition of oxidative stress and inflammation.[70]


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