Dose-related side effects
Depakote is one of the standard epilepsy medicines, and many people who take Depakote (and the other forms of valproate) experience few side effects and enjoy improved control of their seizures. The most common side effects include:

• tiredness
• dizziness
• nausea
• vomiting
• tremor
• hair loss
• weight gain
• behavioral changes (depression in adults, irritability in children)

Some other side effects mentioned even less often are:

• elevated blood ammonia levels, suggested by sleepiness, headache, confusion, or nausea
• reduced attentiveness and response accuracy

Tiredness occurs in many individuals and is often associated with high doses and blood levels. Tiredness can include a range of effects, including slower mental processing speed and less "perkiness" and "spontaneity" in behavior. Large reductions in mental processing speed are uncommon. Effects on "motivation" and "perkiness" are very hard to measure, but they are usually mild and are not common. Patients with new prescriptions for Depakote should be advised to be careful with driving and similar activities until they know whether their abilities are affected.

Nausea is common when therapy begins but is usually less troublesome with Depakote or Depakote ER than with Depakene. Starting at a very low dosage or taking the medicine on a full stomach may help to reduce nausea. Vomiting is less common but occurs in susceptible individuals. Stomach upset from Depakote is more likely when another medication with similar side effects (for example, carbamazepine or felbamate) is also being used.

Tremor is related to blood level and individual susceptibility. Usually the tremor is a fine, rapid intention tremor. Large, slow tremors can also occur, however, sometimes at rest. The tremors tend to fluctuate widely over the course of the day, probably reflecting fluctuations in valproate blood levels as well as other factors that worsen tremor, such as anxiety, caffeine, or low blood sugar. If Depakote is critical for achieving seizure control in a particular patient but the tremor is troublesome, drugs to treat tremor (such as propranolol or primidone [Mysoline]) may be used. These may contribute to other side effects, however.

Weight gain is one of the most vexing side effects of Depakote, affecting 30% to 50% of patients. It is more common in adult women but it also affects men and sometimes even children. Studies suggest that both increased appetite and decreased metabolism can contribute. The average gain for adults is 15 pounds. Exercise and a reduced-calorie diet can be very helpful. It remains uncertain whether weight gain is greater when higher doses of Depakote are taken.

Hair loss occurs in 5% to 10% of patients taking Depakote. It is uncertain whether more hair is lost when higher doses of Depakote are taken. The hair almost always grows back after the Depakote is stopped, but it often has a different texture. (For example, it may grow in curly instead of straight.) Taking selenium (10-20 mcg per day) and zinc (25-50 mg per day) helps some people to prevent hair loss.

Long-term use of valproate has been linked to bone loss, ankle swelling, irregular menstruation, and polycystic ovary syndrome (PCOS). Taking supplements of both calcium and vitamin D may help to prevent bone loss. Patients who have taken Depekote or other forms of valproate for more than 5 years may be advised to have a bone density test. If the test shows significant thinning of the bones, referral to a bone metabolism specialist may be indicated.

Idiosyncratic reactions
Allergic reactions such as rashes are less common with Depakote and other forms of valproate than with most other antiepileptic drugs. Patients should be advised to report rashes, however, especially early in the course of treatment.

Some other rare but life-threatening disorders do occur with the use of this medication. Children younger than 2 years of age and those taking other seizure medications in addition to Depakote are at highest risk. See Serious side effects.