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Depakote Withdrawal Symptoms

WARNING: The FDA advises to never abruptly stop using Depakote or any anti-convulsive except where a life-threatening condition requires immediate cessation.2 Always get medical advice and guidance before gradually stopping an antiepileptic, anticonvulsive drug.

Medical literature on Depakote withdrawal is extremely limited. We have attempted to collate as much information as possible below, and we caution that medical oversight is a must for coming off any anticonvulsive or antiseizure medication, regardless of the reasons it may have been prescribed.

Depakote withdrawal symptoms may include:

  • Status epilepticus — a neurological emergency condition in epileptic patients where sudden Depakote withdrawal can cause seizures that do not stop.2,9
  • Improvement in neuropsychological function 10
  • Improved feeling of well-being and considerable psychosocial benefits.11
  • 81% of epileptic trial participants remained seizure-free 41 months after withdrawal and 67% remained seizure-free 60 months after withdrawal.10
  • A published trial was completed on epileptic children aged 4 on average, who were in remission for 2 years, taking antiepileptic medication (which was not named). Rapid (6 weeks) taper results were compared with slow (9 months) taper outcomes. Follow-ups yearly after 5 years showed 15% in the 6-week taper remained seizure-free, and 8% in the 9-month taper remained seizure-free. The small sample size and lack of other details did not allow definite conclusions to be derived on the optimum rate of anticonvulsive withdrawal, and the authors called for further studies on the subject in both children and adults.12
  • Migraine headache 2,13
  • Duncan, Shorvon, and Trimble in their published work in the Karger Medical Journal reported observed withdrawal symptoms for Depakote: anxiety, tachycardia, memory impairment, impaired concentration, insomnia, tension, lack of energy, agitation, depression, irritability, anorexia, twitching, muscle aches, nausea and vomiting, dizziness, feeling faint, tremors, sweating, hyperreflexia (extreme or repeating response to reflex tapping), abnormal gait, photophobia, headache, depersonalization, and an inability to coordinate voluntary movements of the limbs, head, trunk or other precise muscle movements.15

*Depakote is prescribed for bipolar. According to clinical studies, bipolar is often misdiagnosed where other contributing factors are at play and are not investigated thoroughly.3,4


Depakote withdrawal is a largely neglected topic. Depakote (valproic acid) is usually prescribed during a desperate crisis. Typically, little consideration in follow-up care is given as to how to navigate Depakote withdrawal if the drug is no longer useful, or if debilitating Depakote side effects emerge.

Physicians often prescribe mood stabilizers, like Depakote, as a lifetime treatment for a fixed diagnosis. But is this really the best treatment overall?

Do Your Symptoms Require Depakote?
depakote withdrawal
Alternative to Meds has been the voice and science of antipsychotic withdrawal for over 15 years. We have published evidence regarding our success. It is possible that in many cases symptoms can be addressed in ways that are less toxic. It is astounding how many times we find medical conditions that contributed to the patient profile were not investigated prior to being medicated. Toxic accumulations, recreational drug use, and diet are frequently overlooked. Unfortunately, patients were told they needed to be medicated for life without any investigative effort occurring.

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What is Depakote?

We have provided information below for anyone looking for information about Depakote withdrawal symptoms, valproic acid side effects and holistic treatment help for Depakote withdrawal. Depakote comes in 5 different oral forms, given here in descending order of absorption rates:

VPA syrup:  (valproic acid)

VPA capsule:  (valproic acid)

Divalproex sodium sprinkles Depakote sprinkles come in a capsule that can be opened and added to soft food

Divalproex sodium enteric-coated – delayed-release tablet

Divalproex sodium ER – extended-release tablet

You will find more information below regarding drug classification, information about its mechanism of action, long-term effects, and other treatment information including holistic treatment for Depakote withdrawal. Depakote is an FDA-approved anti-seizure (antiepileptic) medication.2

Black box warnings: include fatal liver disease, major birth defects such as spina bifida and neural tube malformations, and rapidly emerging life-threatening pancreatitis in all age groups. Though not included in the black box, a nearly doubled risk compared to placebo for suicidal thinking and behavior has been demonstrated in clinical trials in all populations.2,16

What is Depakote Used For?

Depakote is used in the treatment of seizure disorders, such as epilepsy, often in combination with other medications.

The FDA approved Depakote for the treatment of bipolar disorder after an unspecified number of 3-week long trials.2 Bipolar disorder has a high propensity for misdiagnosis.3,4 Manic episodes might be considered a bipolar symptom and are described as distinct periods of abnormally sustained elevated mood and other characteristics including irritability and hostility. Other mania symptoms include machine gun-type speech, reduced need to sleep, grandiosity, absence of good judgment, motor hyperactivity, and what can appear to be an expansive flood of fanciful ideas. Depakote was not safety-tested for longer 3-weeks for mania and cautions closely monitoring and reevaluating the usefulness of Depakote for a patient in this situation.2

depakote side effects pregnantDepakote is also approved for the prevention of migraine headaches in adults and children. Please see notes in the holistic treatment section of this article for documented efficacious holistic headache treatments that do not include antipsychotic or antiseizure medications.

Please note: Depakote is not recommended for pregnant women or women of child-bearing age for any reason due to the risks to what is now termed “fetal valproate syndrome.” Children born to mothers taking valproate during pregnancy may suffer withdrawals at birth, and there is a high risk for the baby to be born with birth defects or other medical problems. These adverse events were documented in clinical trials authored by Thisted and Ebbeson, and as reported by the National Organization of Rare Diseases.2,5,19,20

Depakote is sometimes used as an adjunctive or add-on medication in the management of schizophrenia, psychosis, or other psychiatric disorders. particular caution is advised when other medications are prescribed as they may slow or speed up the rate at which Depakote is metabolized.

Off-label uses include the treatment of alcohol or other drug dependencies, diabetic neuropathy, and to quell impulsivity and aggressive behavior such as after traumatic brain injury, based on rat studies showing decreased permeability of the blood-brain barrier in rats who were given impacts to the brain with an electromagnetic cortical-impact device followed by valproate, and another study linking valproate with a decrease in neuronal damage after inducing continuous and repeated electrically-induced seizures in rats.16,17,18 Where a drug does not have an accessible and robust body of documentation concerning human long-term clinical trials to rely on, one would be well-advised to do one’s own research on such medication as carefully and as thoroughly as possible to make informed decisions about starting or stopping such drugs. Additional important information on these topics follows.

Notes on Depakote and Bipolar

It is vital to note that Depakote (valproate) was approved for treating bipolar disorder after only very short trials were done on hospitalized acute mania patients. No long-term trials were ever completed that demonstrated the long-term safety or effectiveness of Depakote. Nonetheless, Depakote has been prescribed to millions of people since its approval in 1983. There is a much larger body of evidence that has accumulated post-marketing of the drug that includes adverse side effects, symptoms of withdrawal, and other information below.

Always seek reliable medical advice before starting or stopping a prescription drug such as Depakote, and before adding other medications that may interact and cause unexpected reactions.

Discontinuing/Quitting Depakote

getting off depakoteIt may become necessary or desirable to stop Depakote. How to quit Depakote and Depakote alternatives are what we specialize in at Alternative to Meds Center. We have protocols for tapering Depakote and bridging over to natural alternatives to Depakote that can make the withdrawal from Depakote gentle and sustainable. Except in certain circumstances where immediate cessation is required to save the patient’s life, such as liver failure, life-threatening pancreatitis, or other conditions, Depakote should be gently tapered off with proper monitoring, support, and guidance.

The FDA label indicates that where hepatic dysfunction, pancreatitis, toxic levels of ammonia or other life-threatening conditions emerge, Depakote should be immediately stopped.2

If tapering is done correctly it can be a mild procedure. Done too fast, it can be extremely difficult and can introduce undesirable risks to health.

Depakote Alternative Names and Slang

Other trade names for the generic valproate, sodium valproate, or Divalproex delayed-release, include Depakene, Depakote ER (extended-release), Depakote Sprinkles, Stavzor, and Alti-Valproic.

The drug is available in a soft-gel capsule, tablet, or syrup form. Depakote Sprinkles are designed so that if a person cannot swallow a capsule or tablet, the drug can be sprinkled on applesauce or other types of soft food. One capsule of Sprinkles is meant to be used all at once.

Depakote Side Effects

depakote side effectsDepakote is often administered as an adjunctive medication, for instance with antipsychotics, SSRIs, SNRIs, or other mood-stabilizing drugs. It may be difficult to ascertain in such circumstances exactly what drug is causing what side effect; therefore each patient should be monitored carefully in this regard for reactions needing medical attention.

The FDA2 has published some known adverse side effects that require careful monitoring while on Depakote, including:

  • Hepatotoxicity:  liver failure, leading to fatality, which may follow symptoms such as weakness, lethargy, vomiting, anorexia, and facial edema. Especially if a person has a prior history of liver disease, regular physical examinations, as well as serum liver tests, should be done to monitor the person closely for signs of liver toxicity.
  • Birth defects are linked to taking Depakote during pregnancy, where the infant may develop deformities of the limbs, heart, craniofacial, and neural tube defects leading to spina bifida, and others. Birth defects occur 4 times higher where mothers took Depakote compared to other epileptic medications.
  • Lowered cognitive scores after in utero exposure to Depakote:  have been studied and shown as significantly lower in children born to epileptic mothers taking Depakote compared to children born to mothers taking some other AED or no AED. Since it has not been established if there is a specific period of risk during pregnancy for such birth defects including lowered IQ, the consensus is that women of child-bearing age should not be prescribed Depakote. However, should pregnancy occur while on a prescription of Depakote, the drug should not be withdrawn abruptly due to risk of seizure and other reactions, and possible fatality to the fetus.
  • Fatal pancreatitis:  in both adult and children are linked to Depakote. Where this condition presents, it can progress rapidly and is considered life-threatening, requiring immediate hospitalization. Some warning signs of pancreatitis can include nausea, vomiting, pain in the abdomen, anorexia, and the patient should be immediately evaluated for hemorrhages and other symptoms of pancreatitis.
  • Suicidality:  a two-fold increase in suicidal ideation and behavior in both adults and children. Four suicides occurred within a twelve-week trial.
  • Abnormal bleeding
  • Hypothermia
  • Other:  side effects include rash, somnolence in the elderly, dizziness, indigestion.

Depakote FAQs

Below, some information is provided regarding the most frequently asked questions about Depakote, concerning the mechanism of action, how it can affect the body adversely, and other things to be aware of if you are considering Depakote withdrawal.

How Does Depakote Work?

It is thought that Depakote acts on GABA levels in the CNS. GABA is a natural brain chemical with a calming effect that helps to sedate a person experiencing episodes of mania. This is thought to occur because valproic acid may reduce the rapid-firing of neurons by sodium, potassium, and calcium channel blockades.22

Is Depakote an Antipsychotic?

No, Depakote is technically classified as a branched fatty acid with anticonvulsive and antimanic properties.23 It is most often referred to as a first-generation antiepileptic, or AED. It is often prescribed along with antipsychotic medications, as well as SSRI’s and SNRI’s in treating certain disorders.

Depakote works largely on increasing GABA permeability, which results in a calming effect on the central nervous system. That is why it is sometimes used while helping a patient to withdraw from antipsychotics or other drugs. The calming effect helps to counterbalance the excitatory surge of dopamine and other neurochemical stimulation that can occur during antipsychotic drug withdrawal.

Is Depakote a Mood Stabilizer?

Yes. Along with lithium and Lamictal, Depakote belongs to a group of drugs referred to as mood stabilizers. These types of drugs are used in the treatment of bipolar manic episodes that require sedation and possible hospitalization to help stabilize the person.

Can Depakote Make You Gain Weight?

Yes, Depakote is associated with weight gain in the first three months, and is more pronounced in females compared to males. Noting weight changes before and during treatment is a recommended monitoring practice for epileptic and other patients taking Depakote.1

Does Depakote Damage the Liver?

There is significant documented evidence concerning liver damage, toxicity and death related to some patients prescribed Depakote. 2

What are the Symptoms of Depakote Toxicity?

Depakote toxicity of valproic acid overdose symptoms can include edema in the brain, depressed respiratory system, nausea, vomiting, lethargy, chills, hallucinations, confusion, headache, irritability, seizures, somnolence, twitches or jerking motions and can result in coma and death.24

It may be important to note that aspirin taken concurrently will elevate valproate levels and this interaction could result in a significant risk of toxicity. 2,24

Immediate medical attention without delay is required the moment these Depakote toxicity symptoms emerge.

Can Depakote Withdrawal be done ‘Cold Turkey?’

Never abruptly stop the medication unless this is required to prevent fatality. In the case of needing to stop Depakote because of possible fatal side effects, stopping the medication would best be done in an appropriate medical facility where life-saving protocols are immediately available.

Always speak to your doctor before deciding to stop Depakote. If your doctor is resistant to assist despite your desire to quit, it may be pragmatic to consult a more integrative doctor for a second opinion.

Safe Treatment for Depakote Withdrawal – Holistic Help

root cause of addictionAt Alternative to Meds Center, our goal is to help people safely taper off medications to zero, where possible, in a comfortable and compassionate setting. The center is staffed by doctors, nurses, therapists, and caregivers who are well-versed in gentle and effective tapering protocols.

As a fundamental aspect of Depakote withdrawal, we also want to investigate the root causes for the symptoms that led to prescription medication in the first place. Headache sufferers who have been prescribed heavy drugs like Depakote, may be interested in research published on how certain nutrient deficiencies are directly linked to migraine and other types of chronic debilitating headaches. For example, in a study published in the Journal of Head and Face Pain, Mauskop et al found 80% of their trial participants experienced headache relief within 15 minutes of intravenous magnesium sulfate.21 In their book “Magnesium in Headache,” authors Yablon et al further demonstrate the benefits of magnesium in treating migraine headache in this free book published by the Adelaide University Press.14

The health goals of the individual are of primary importance at our center. Using such protocols as holistic neurotransmitter replacement therapy, toxicity removal, testing for and correcting nutritional deficits, IV treatments, and many other helpful holistic techniques, we can help a person regain optimal health, while at the same reducing the need for prescription drugs.

Each person has uniqueness in their make-up, genetic profile, sensitivities, strengths, and personal goals. That is why each client at the center receives a treatment plan tailored to meet those goals.

More information is available on request, and we would welcome further inquiries for more details on our therapies and treatments for Depakote withdrawal that Alternative to Meds Center could provide you for your bridge back to the best levels of health with the least amount of prescription medication possible.


1.  Verrotti A, D’Egidio C, Mohn A, Coppola G, Chiarelli F. Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications. Obes Rev. 2011 May;12(5):e32-43. doi: 10.1111/j.1467-789X.2010.00800.x. Epub 2010 Sep 6. PMID: 20880119. [cited 2021 July 13]

2. FDA label Depakote (divalproex sodium) 1983 [cited 2021 July 13]

3. Shen H, et al., “Analysis of Misdiagnosis of Bipolar Disorder in an Outpatient Setting.” Shanghai Arch Psychiatry April 25 2018 PMID 29736129 [cited 2021 July 13]

4. Bowden CL. “Strategies to reduce misdiagnosis of bipolar depression.” Psychiatr Serv. 2001 Jan;52(1):51-5. doi: 10.1176/appi.ps.52.1.51. PMID: 11141528. [cited 2021 July 13]

5. Osterweil N, “Depakote Has High Birth Defects Rate Among Antiepileptics.” MedpageToday [online} August 8 2006 [cited 2021 July 13]

6. Schwartz TL, Massa JL, Gupta S, Al-Samarrai S, Devitt P, Masand PS. Divalproex Sodium Versus Valproic Acid in Hospital Treatment of Psychotic Disorders. Prim Care Companion J Clin Psychiatry. 2000;2(2):45-48. doi:10.4088/pcc.v02n0203 [cited 2021 July 13]

7. Sherr JD, Kelly DL. Substitution of immediate-release valproic acid for divalproex sodium for adult psychiatric inpatients. Psychiatr Serv. 1998 Oct;49(10):1355-7. doi: 10.1176/ps.49.10.1355. PMID: 9779912. [cited 2021 July 13]

8. Rahman M, Nguyen H. Valproic Acid. [Updated 2021 Jan 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559112/ [cited 2021 July 13]

9. Wylie T, Sandhu DS, Murr N. Status Epilepticus. 2021 May 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 28613459. [cited 2021 July 13]

10. Lossius MI, Hessen E, Mowinckel P, Stavem K, Erikssen J, Gulbrandsen P, Gjerstad L. Consequences of antiepileptic drug withdrawal: a randomized, double-blind study (Akershus Study). Epilepsia. 2008 Mar;49(3):455-63. doi: 10.1111/j.1528-1167.2007.01323.x. Epub 2007 Sep 19. PMID: 17888074. [cited 2021 July 13]

11. Jacoby A, Johnson A, Chadwick D. Psychosocial outcomes of antiepileptic drug discontinuation. The Medical Research Council Antiepileptic Drug Withdrawal Study Group. Epilepsia. 1992 Nov-Dec;33(6):1123-31. doi: 10.1111/j.1528-1157.1992.tb01769.x. PMID: 1464274. [cited 2021 July 13]

12. Ranganathan LN, Ramaratnam S. Rapid versus slow withdrawal of antiepileptic drugs. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD005003. doi: 10.1002/14651858.CD005003.pub2. PMID: 16625621. [cited 2021 July 13]

13. Pavese N, Baracchini G, Bonuccelli U. Valproate-withdrawal induced migraine. Headache. 1994 Jul-Aug;34(7):445. doi: 10.1111/j.1526-4610.1994.hed3407445_1.x. PMID: 7928333. [cited 2021 July 13]

14. Yablon LA, Mauskop A. Magnesium in headache. In: Vink R, Nechifor M, editors. Magnesium in the Central Nervous System [Internet]. Adelaide (AU): University of Adelaide Press; 2011. PMID: 29920023. [cited 2021 July 13]

15. Duncan JS, Shorvon SD, Trimble MR. Withdrawal symptoms from phenytoin, carbamazepine and sodium valproate. J Neurol Neurosurg Psychiatry. 1988 Jul;51(7):924-8. doi: 10.1136/jnnp.51.7.924. PMID: 3144581; PMCID: PMC1033195. [cited 2021 July 13]

16. NAMI information sheet, “Valproate (Depakote)” June 2019 [online] [cited 2021 July 15]

17. Dash PK, Orsi SA, Zhang M, et al. Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in ratsPLoS One. 2010;5(6):e11383. Published 2010 Jun 30. doi:10.1371/journal.pone.0011383 [cited 2021 July 15]

18. Brandt C, Gastens AM, Sun Mz, Hausknecht M, Löscher W. Treatment with valproate after status epilepticus: effect on neuronal damage, epileptogenesis, and behavioral alterations in rats. Neuropharmacology. 2006 Sep;51(4):789-804. doi: 10.1016/j.neuropharm.2006.05.021. Epub 2006 Jun 27. PMID: 16806297. [cited 2021 July 15]

19. NORD authors, “Fetal Valproate Syndrome” [online] 2020 [cited 2021 July 15]

20. Thisted E, Ebbesen F. Malformations, withdrawal manifestations, and hypoglycaemia after exposure to valproate in utero. Arch Dis Child. 1993 Sep;69(3 Spec No):288-91. doi: 10.1136/adc.69.3_spec_no.288. PMID: 8215567; PMCID: PMC1029494. [cited 2021 July 15]

21. Mauskop A, Altura B, Cracco R, Altura BM, “Intravenous Magnesium Sulfate Rapidly Alleviates Headaches of  Various Types”  Headache Journal of Head and Face Pain March 1998 [online] [cited 2021 July 15]

22. Rahman M, Nguyen H. Valproic Acid. [Updated 2021 Jan 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559112/ [cited 2021 July 15]

23. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 3121, Valproic acid. Retrieved July 15, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/Valproic-acid. [cited 2021 July 15]

24. Patel AR, Nagalli S. Valproate Toxicity. [Updated 2021 Apr 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560898/ [cited 2021 July 15]


Originally Published Sep 13, 2018 by Diane Ridaeus


This content has been reviewed and approved by a licensed physician.

Dr. John Motl, M.D.

Dr. Motl is currently certified by the American Board of Psychiatry and Neurology in Psychiatry, and Board eligible in Neurology and licensed in the state of Arizona.  He holds a Bachelor of Science degree with a major in biology and minors in chemistry and philosophy. He graduated from Creighton University School of Medicine with a Doctor of Medicine.  Dr. Motl has studied Medical Acupuncture at the Colorado School of Traditional Chinese Medicine and at U.C.L.A.

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Depakote Withdrawal Symptoms, Valproic Acid Side Effects, Treatment Help
Medical Disclaimer:
Nothing on this Website is intended to be taken as medical advice. The information provided on the website is intended to encourage, not replace, direct patient-health professional relationships. Always consult with your doctor before altering your medications. Adding nutritional supplements may alter the effect of medication. Any medication changes should be done only after proper evaluation and under medical supervision.

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