FDA Date: 05/06/2013 Show
Valproate Anti-seizure Products FDA Drug Safety CommunicationValproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ Scores in Exposed Children This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available. The U.S. Food and Drug Administration (FDA) is advising health care professionals and women that the anti-seizure medication valproate sodium and related products, valproic acid and divalproex sodium, are contraindicated and should not be taken by pregnant women for the prevention of migraine headaches. Based on information from a recent study, there is evidence that these medications can cause decreased IQ scores in children whose mothers took them while pregnant. Stronger warnings about use during pregnancy will be added to the drug labels, and valproate's pregnancy category for migraine use will be changed from "D" (the potential benefit of the drug in pregnant women may be acceptable despite its potential risks) to "X" (the risk of use in pregnant women clearly outweighs any possible benefit of the drug). With regard to valproate use in pregnant women with epilepsy or bipolar disorder, valproate products should only be prescribed if other medications are not effective in treating the condition or are otherwise unacceptable. Valproate products will remain in pregnancy category D for treating epilepsy and manic episodes associated with bipolar disorder. With regard to women of childbearing age who are not pregnant, valproate should not be taken for any condition unless the drug is essential to the management of the woman's medical condition. All non-pregnant women of childbearing age taking valproate products should use effective birth control. Valproate products include: valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics. This alert is based on the final results of the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study showing that children exposed to valproate products while their mothers were pregnant had decreased IQs at age 6 compared to children exposed to other anti-epileptic drugs. The difference in average IQ between the children who had been exposed to valproate and the children who had been exposed to other antiepileptic drugs varied between 8 and 11 points depending on the drug to which valproate was compared. FDA previously communicated initial findings about this risk in a June 2011 Drug Safety Communication. At that time, FDA also worked with valproate manufacturers to revise the drug labels after interim results from the NEAD study showed lower cognitive test scores at age 3 in children exposed to valproate compared to children exposed to other antiepileptic drugs. Women who are pregnant and taking a valproate medication should not stop their medication but should talk to their health care professionals immediately. Stopping valproate treatment suddenly can cause serious and life-threatening medical problems to the woman or her baby. It is not known whether there is a specific time period during pregnancy when valproate exposure can result in negative cognitive effects. Similarly, there is no known time during pregnancy in which exposure may be considered to have less risk for decreased IQ in children. Because the women in the NEAD study were exposed to antiepileptic drugs throughout pregnancy, whether the risk for decreased IQ was related to a particular time period during pregnancy could not be assessed. FDA is working with manufacturers to change the drug labels for valproate products with this updated risk information. FDA continues to evaluate information about the potential risks of valproate use during pregnancy and will update the public as more information becomes available. View the full FDA Drug Safety Communication on FDA.gov Alternative to Meds Does Not Provide Rapid DetoxThere are, rarely, instances when rapid or abrupt discontinuation of a drug like Depakote is medically necessary to save the life of the patient. For example, anticonvulsant-induced movement disorders, and other potentially life-threatening reactions such as Stevens-Johnson syndrome are rare but are known adverse events associated with Depakote. These must be treated in a hospital setting such as an emergency ward or ICU where abrupt discontinuation is most safely achieved.4,28 Alternative to Meds cannot provide the emergency medical treatment that is needed for rapid withdrawal in such cases, and we are not in a position to give guidance regarding rapid Depakote withdrawal. Begin Depakote tapering only when you are in a stable condition.It is best to begin a Depakote taper when the person is reasonably tolerating the medication, sleeping well, eating regularly, doing regular exercise, is under competent medical oversight from a willing prescriber. The best candidate would have eliminated caffeine and other stimulants, alcohol use, marijuana, or other recreational drug use because these substances can interact with and interfere with the medication’s mechanisms of action. This can throw a wrench into any taper program. having a support circle is extremely beneficial for support from family, close friends, and sympathetic mentors. Also arranging one’s life in an organized fashion might include engaging in hobbies or light work to focus on. If you are not sleeping well, that should be taken care of with the help of your prescriber or using holistic means that work well for you beforehand. Contracting for safety — what it means.A person in a manic state may become unwilling or unable to follow directions. However, following directions is vital for a successful taper. It is recommended to discuss and voluntarily draw up a written contract that can be presented when needed. Putting this solid commitment in writing to agree to follow the doctor’s tapering directions can get things back on track. For example, if the person has stopped their meds and has become manic or psychotic, they may become unwilling to continue the taper as agreed. This is a safety risk for the person that the contract for safety was put in place to remedy. Part of the agreement would be to acknowledge that non-compliance will result in police involvement, or having to go to the hospital. For the person’s own safety and those around them, the contract for safety is a vital safety net for anyone tapering from ACDs and other unpredictable neuroleptic drugs.20 Set up medical support before your Depakote taper.There are holistic psychiatrists and other prescribers who can assist you with an outpatient-style taper. Certainly, we recommend inpatient care when possible, but we know it may not always be possible or practical for everyone. When you find your outpatient doctor, you are welcome to share our information with them if you like, and we hope it helps open the discussion. Eliminate all forms of caffeine or other stimulants, and recreational drugs.This is so important it probably should be #1 on the list of guidelines. Use of stimulants, even too much coffee, tea, or soft drinks, alcohol or recreational drug use, can all potentially land you in the hospital. This is because of the mechanics of how stimulants and alcohol impact Depakote, resulting in a flood of excitatory neurochemicals. Restrict these items and stay safe.15,18,19 Food choices to control blood sugar spikes.Blood sugar spikes and crashes can disrupt tapering with a vengeance. Choose low-glycemic, protein-based foods and snacks to prevent unnecessary problems. Don’t let hunger disrupt your progress. Breakfast should be protein-based giving a good start to the day. Follow up with smaller protein-based meals that also incorporate your favorite vegetables throughout the day. Experiment with some rutabaga or cauliflower for “mashed potatoes” — delicious with butter! Avoid refined flours and sugars or find low-carb replacements. Snacks like non-starchy veggies, peanut butter, avocado, raspberries, blueberries, dill pickles, cheeses, delicious cold cuts, and other sugar-free foods can deliciously fill in the gaps as needed.13 Many Benefits of Exercise.Exercise has been documented well for the benefits to physical and mental health. For example, Sharma et al’s comprehensive summary24 of benefits lists improved mood, energy, and better sleep that should be emphasized and encouraged by mental health professionals. In addition to these benefits, Albrecht Messerschmidt’s 2010 book, Comprehensive Natural Products II, discusses the role of oxygen in certain chemical reactions, such as modulating dopamine molecules.25 This would be a very good reason to blend some aerobic, cardio exercise into the daily routine where a person with excess dopamine may benefit from this regulatory function. According to Science Daily, regulating the “happy hormone” dopamine is important. Too little dopamine is linked to Parkinson’s disease, and too much dopamine is linked to mania, hallucination, or other psychiatric symptoms. Exercise is an extremely good tool that can help regulate this important hormone.26 Use the smallest milligram dose of Depakote available to use for the taper.The smallest milligram dose of Depakote is the dark pink oval 125mg tablet. This does not mean you want to drop to the lowest dose. Smaller pills will help configure the medication total accurately. For example, if you are on 1500mg Depakote, you will want to have the 125mg version available so that if you were to drop down to 1375mg, you could take two of the 500mg (for 1000mg), cut one of the 500mg in half (for 250mg), and then add one of the 125mg to equal a total of 1375mg. It also might be that you get the 250mg and the 125mg versions prescribed to make the math easier. You can cut the Depakote 125mg in half giving you 62.5mg. These small cuts are not necessary for everyone, but for some, slowing it way down is the only path to re-regulation after the use of the drug. You can cut any of the Depakote versions in half to configure the correct milligram dosing needed. However, if you are on Depakote ER when you cut the pill, it will lose the extended-release attribute. They do make a 250mg Depakote ER version. So if you are on the ER version, many people can configure the tapering dosing amount in 250mg increments. If you are planning to make smaller than 250mg cuts, the regular non-time-released version would be likely easier for that purpose. So let’s say a person is trying to get to 875mg. They might take three 250mg Depakote ER, and 125mg Depakote (non-time-release), for a total of 875mg. These configurations can be worked out with your prescribing physician for accuracy of dosage. Keep a written record — don’t rely on “mental math” in the middle of a Depakote taper. Other medications you are on.The CDC reported that between 2015 and 2018 about 24% of the US population took 3 or more medications over a 30-day period, and over 12% took 5 or more medications in the same period. It is not at all unlikely that a person who has been taking Depakote for some time may have also been prescribed other medications for various reasons. Tapering within an inpatient setting would be particularly advised in this case. The order or sequence of which medications to taper is vital so as not to overwhelm the body by introducing too much change all at once. These matters can be assessed and managed more easily in an inpatient setting, as both the micro-changes and the broader modifications can be made when needed on an immediate basis.21 In any case it would be advised to speak with your prescribing doctor who is helping with your taper and discuss the best sequence, depending on what medications were prescribed and for what reasons they were originally prescribed. Factors that would have to be considered include how long a person was taking each drug, the symptoms the person was attempting to control, current symptoms, and other issues that are unique to each individual. How long will Depakote tapering last?Because each person has unique biomarkers, genetic profile, medical history, sensitivities, individualized sets of symptoms, and so on, there is no “one-size-fits-all” when it comes to Depakote tapering. Like maneuvering down a mountain road, sometimes shifting to a lower gear is more effective than slamming on the brakes too aggressively. Slow and safe are the keywords to keep in mind. Some medications may take months, or even years to resolve as demonstrated in benzodiazepine clinical studies,22 as well as studies on discontinuation of mood stabilizers.23 However, we have observed that when effective tapering support is provided, these numbers typically decrease as the body is maximally assisted in the rehabilitation of its normal neurochemistry. Red Flags of Depakote TaperingReturning to our analogy of driving a logging truck down a mountain with switchbacks on an icy road, you have to go light on the accelerator — go slow — and be ready to use your brakes. If you are a patient, skillful driver, you will get safely down the mountain. Free-wheeling it will likely end in a crash — an avoidable disaster. Accelerating around the turns because it feels good can turn out like the wreck that you would anticipate in our driving scenario. We observe similar laws of gravity and inertia involved in Depakote tapering. Go slow so you can get down the mountain. That is the over-arching axiom. Not eating, not sleeping, intense side effects, and perseverating (obsessing) over a certain topic that will not leave your mind are all red flags. These are signs you are heading into the danger zone. For instance, after the second day of not sleeping, that could be a signal to pay attention to. It may be that you need to go back up on your medications. Then you can work your way back to the earlier dose. Please talk to your prescriber about the likelihood of encountering these moments of crisis before you begin Depakote tapering so you have a better understanding of what to expect. Don’t try to figure it out mid-crisis. You don’t want to end up in the hospital back at square one. If you begin to feel you pose a danger to yourself or those around you, just play it safe and get checked in the hospital. Hospitalization is not a failure. It could be that being medication-free is not the best outcome. Or it could signal that a much longer withdrawal period is needed. Watch for red flags and respond to them by collaborating with your prescriber without delay. Bridge medications for Depakote tapering.Some persons may do well using what are referred to as bridge medications to ease Depakote withdrawal. At Alternative to Meds Center, various methods of tapering can safely ease withdrawal issues and bridge medications can be designed on an individual basis. Limiting stimulating media during Depakote Tapering.Wrestling with life questions, religious matters, and watching over-stimulating movies or TV, can all be overwhelming for someone attempting Depakote tapering. Better activities might include outside walking, physical activity, hobbies you enjoy, light reading, light work, or things that can pleasantly extrovert the attention. These types of activities can act as grounding elements that support your tapering process very well. Depakote Alternatives and Depakote Withdrawal LinksWe have pages on our site that address Depakote alternatives that can be used during the tapering process. We strongly recommend you review these pages. Quick links are
Antipsychotic Alternatives for general information on nutrition, etc., and Depakote Alternatives. You may also want to consider reading the
Depakote Withdrawal page. Depakote Side Effects
Notes on Rebound Symptoms after Stopping Depakote Too Quickly.For a person with epilepsy to abruptly stop or even reduce Depakote, one of the most concerning reactions is episodes of seizures that do not stop, also called status epilepticus.6 For bipolar persons, a sudden cessation of Depakote can bring on a return of the person’s original symptoms such as mania, insomnia, etc. A person who was taking Depakote as a treatment for migraines may have
a return of migraines, which may be considerably more severe than before taking valproate. A person taking Depakote as a mood stabilizer, for bipolar, for headaches, or for other conditions may find that reducing the drug too quickly can cause intense reactions. Sometimes these withdrawal adverse effects can linger on if they are not addressed in a healthy way as part of the tapering process.7 Depakote Withdrawal SymptomsDepakote withdrawals can include both rebound (returning) symptoms and new symptoms, including the following:
Slowly reducing the medication with other support mechanisms in place are the means used to offset these reactions. WARNING: Never abruptly or quickly stop taking Depakote. Find help to assist you with the challenges of Depakote tapering or coming off any psychoactive substance. What is Depakote?While this anticonvulsant drug is not a benzodiazepine, in their 2021 book entitled “Valproic Acid.” Rahman and Nguyen conclude that the mechanism of action is in some ways similar, and
involves the control of GABA distribution (and other neurochemicals) along the CNS.10 GABA is a calming natural chemical, though the complex mechanism of action and its interactions with other transmitters and molecules and messaging systems are not entirely understood. Its calming properties make it useful in acute situations such as alcohol withdrawal, where controlling symptoms of alcohol withdrawal is desired without the use of benzodiazepines.11 Contact Alternative to Meds CenterYou or your loved one may be struggling with side effects, tolerance, or other issues that may be blocking your ability to enjoy natural mental health and be truly well. You owe it to yourself to find out more about how the Alternative to Meds Depakote tapering program works, whether you feel you would be a good candidate, and how it could possibly assist you to overcome these challenges. What should be monitored when taking Depakote?Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence.
What are the nursing considerations for valproic acid?Nursing considerations. History: Hypersensitivity to valproic acid; hepatic impairment; pregnancy, lactation.. Physical: Weight; skin color, lesions; orientation, affect, reflexes; bowel sounds, normal output; CBC and differential, bleeding time tests, LFTs, serum ammonia level, exocrine pancreatic function tests, EEG.. What two adverse reactions should a patient be told who are taking Depakote?A: Common side effects experienced with Depakote include drowsiness, nausea, abdominal pain, diarrhea, vomiting, low platelet count, tremors, tiredness, and hair loss. The side effects may be mild to moderate, but they may also be signs of a more serious condition.
What should I avoid while taking Depakote?But your doctor might recommend that you avoid alcohol while taking either of these drugs. This is because drowsiness or dizziness are side effects of Depakote, Depakote ER, and alcohol. So, combining alcohol with either of these drugs may make any drowsiness or dizziness that you experience worse.
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