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Depakote Side Effects

Generic Name: divalproex sodium

Note: This page contains information about the side effects of divalproex sodium. Some of the dosage forms included on this document may not apply to the brand name Depakote.

Not all side effects for Depakote may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to divalproex sodium: oral capsule delayed release, oral syrup, oral tablet delayed release, oral tablet enteric coated, oral tablet extended release

In addition to its needed effects, some unwanted effects may be caused by divalproex sodium (the active ingredient contained in Depakote). In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking divalproex sodium:

More common
  • Black, tarry stools
  • bleeding gums
  • bloating or swelling of the face, arms, hands, lower legs, or feet
  • blood in the urine or stools
  • confusion
  • cough or hoarseness
  • crying
  • delusions
  • dementia
  • depersonalization
  • diarrhea
  • difficult or labored breathing
  • dysphoria
  • euphoria
  • fever or chills
  • general feeling of discomfort or illness
  • headache
  • joint pain
  • loss of appetite
  • lower back or side pain
  • mental depression
  • muscle aches and pains
  • nausea
  • nervousness
  • painful or difficult urination
  • paranoia
  • pinpoint red spots on the skin
  • quick to react or overreact emotionally
  • rapid weight gain
  • rapidly changing moods
  • runny nose
  • shakiness in the legs, arms, hands, or feet
  • shivering
  • sleepiness or unusual drowsiness
  • sore throat
  • sweating
  • tightness in the chest
  • tingling of the hands or feet
  • trembling or shaking of the hands or feet
  • trouble sleeping
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • unusual weight gain or loss
  • vomiting
Less common
  • Abnormal dreams
  • absence of or decrease in body movement
  • anxiety
  • bloody nose
  • blurred vision
  • bruising burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • change in personality
  • change in walking and balance
  • changes in patterns and rhythms of speech
  • chest pain
  • chills
  • cloudy urine
  • clumsiness or unsteadiness
  • cold sweats
  • constipation
  • darkened urine
  • degenerative disease of the joint
  • difficulty with moving
  • dizziness
  • dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
  • dry mouth
  • excessive muscle tone
  • fast, irregular, pounding, or racing heartbeat or pulse
  • feeling of warmth or heat
  • flushing or redness of the skin, especially on the face and neck
  • frequent urge to urinate
  • heavy non-menstrual vaginal bleeding
  • hyperventilation
  • increased need to urinate
  • indigestion
  • lack of coordination
  • large, flat, blue or purplish patches in the skin
  • leg cramps
  • lip smacking or puckering
  • loss of bladder control
  • loss of strength or energy
  • multiple swollen and inflamed skin lesions
  • muscle pain or stiffness
  • muscle tension or tightness
  • normal menstrual bleeding occurring earlier, possibly lasting longer than expected
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • passing urine more often
  • pounding in the ears
  • puffing of the cheeks
  • rapid or worm-like movements of the tongue
  • rapid weight gain
  • restlessness
  • seeing, hearing, or feeling things that are not there
  • shakiness and unsteady walk
  • slurred speech
  • small red or purple spots on the skin
  • sweating
  • swollen joints
  • trouble with speaking
  • twitching
  • uncontrolled chewing movements
  • uncontrolled movements of the arms and legs
  • unsteadiness, trembling, or other problems with muscle control or coordination
  • vomiting of blood or material that looks like coffee grounds
  • yellow eyes or skin

If any of the following symptoms of overdose occur while taking divalproex sodium, get emergency help immediately:

Symptoms of overdose
  • Change in consciousness
  • fainting
  • loss of consciousness
  • slow or irregular heartbeat

Some of the side effects that can occur with divalproex sodium may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Acid or sour stomach
  • belching
  • body aches or pain
  • change in vision
  • congestion
  • continuing ringing or buzzing or other unexplained noise in the ears
  • hair loss or thinning of the hair
  • hearing loss
  • heartburn
  • impaired vision
  • lack or loss of strength
  • loss of memory
  • problems with memory
  • rash
  • seeing double
  • tender, swollen glands in the neck
  • trouble with swallowing
  • uncontrolled eye movements
  • voice changes
  • weight gain
  • weight loss
Less common
  • Absent, missed, or irregular menstrual periods
  • back pain
  • burning, dry, or itching eyes
  • change in taste or bad unusual or unpleasant (after) taste
  • coin-shaped lesions on the skin
  • cough producing mucus
  • cramps
  • dandruff
  • discharge or excessive tearing
  • dry skin
  • earache
  • excess air or gas in the stomach or intestines
  • eye pain
  • feeling of constant movement of self or surroundings
  • full feeling
  • heavy bleeding
  • increased appetite
  • itching of the vagina or genital area
  • itching skin
  • loss of bowel control
  • neck pain
  • oily skin
  • pain
  • pain during sexual intercourse
  • pain or tenderness around the eyes and cheekbones
  • passing gas
  • rash with flat lesions or small raised lesions on the skin
  • redness or swelling in the ear
  • redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
  • redness, swelling, or soreness of the tongue
  • sensation of spinning
  • sneezing
  • stiff neck
  • stopping of menstrual bleeding
  • thick, white vaginal discharge with no odor or with a mild odor

For Healthcare Professionals

Applies to divalproex sodium: oral delayed release capsule, oral delayed release tablet, oral tablet extended release


Nausea, vomiting, and indigestion appear less frequently and less severely with divalproex sodium (the active ingredient contained in Depakote) than with valproic acid. These effects may be further attenuated by administering doses with food.[Ref]

Gastrointestinal side effects related to gastritis are common and include nausea, vomiting, and indigestion, especially with the initiation of therapy and with rapid increases in dose. These effects are generally transient and rarely require the discontinuation of therapy. Life threatening pancreatitis has been reported to occur anywhere from shortly after initial use to occurring after several years of use. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Hyperamylasemia occurs in up to 20% of patients and rarely presents as clinical pancreatitis (usually one to six months after initiation of therapy).[Ref]


Hepatic side effects including transient dose-dependent elevations of serum transaminases, amylase, and ammonia have been reported to occur in up to 44% of treated patients. Mild elevations in transaminases and amylase may be managed by dose reductions. Dose-related hepatitis, which is occasionally fatal, has also been reported. Some clinicians recommend monitoring liver function tests at baseline, then monthly during the first 6 months of therapy and every 3 months thereafter. Prompt withdrawal of divalproex sodium (the active ingredient contained in Depakote) is recommended if significant hepatic dysfunction occurs.[Ref]

Risk factors for valproate-associated hepatitis are young age (particularly age less than 2 years old), poor nutritional status, mental retardation, underlying metabolic disease, and concomitant use of other anticonvulsant medications. Characteristic pathological features include microvesicular steatosis.[Ref]

Nervous system

Nervous system side effects including drowsiness, ataxia, and hand tremor have been reported. Cases of encephalopathy (manifested by stupor, coma, hallucinations or affective changes) and chorea have been reported. Reversible sensorineural hearing loss associated with valproate therapy has been reported rarely. Two cases of extrapyramidal disorders have been reported in association with valproate therapy. A case of pseudotumor cerebri has also been reported.[Ref]

Divalproex sodium may inhibit urea synthesis resulting in hyperammonemia, which has been associated with encephalopathy, delirium, and ataxia in rare cases.

Loss of seizure control may indicate associated hepatitis.[Ref]


Hematologic side effects including rare cases of reversible thrombocytopenia associated with antiplatelet antibodies and bone marrow suppression have been reported.[Ref]

Some clinicians recommend monitoring complete blood counts (including platelet counts) at baseline, then monthly for three months, and every three months thereafter.

Data from a study of 265 patients strongly suggests a causal relationship between rising plasma valproic acid levels and reduced platelet counts, with additional risk factors including female gender and lower baseline platelet counts.[Ref]


Respiratory side effects including a case of truncal weakness and respiratory failure has been associated with valproate therapy.[Ref]


Renal side effects including several case reports which suggested that valproate acid may cause Fanconi's syndrome have been reported. Valproate-induced Fanconi's syndrome has been reported more often in children than in adults.[Ref]


Cardiovascular side effects including vasodilation and peripheral edema have been reported.[Ref]


Valproate therapy has been associated with polycystic ovaries, elevated serum testosterone concentrations and menstrual disturbance. One study has suggested that 80% of women treated with valproic acid before the age of 20 have polycystic ovaries or hyperandrogenism.[Ref]

Endocrine side effects including a variety of adverse reproductive endocrine disorders have been reported in epileptic women taking valproic acid.[Ref]


Valproate therapy has been associated with stomatitis and cutaneous leukoclastic vasculitis. A case of psoriasiform eruption has been reported in a patient receiving valproic acid.[Ref]

Dermatologic side effects including transient alopecia and rare rashes have been reported.[Ref]


Musculoskeletal side effects including a case of osteopenia have been reported.[Ref]


General side effects including hypothermia have been reported.


1. "Product Information. Depakote (divalproex sodium)." Abbott Pharmaceutical, Abbott Park, IL.

2. Uddin AB "Drug-induced pseudotumor cerebri." Clin Neuropharmacol 26 (2003): 236-8

3. Nasreddine W, Beydoun A "Valproate-induced thrombocytopenia: a prospective monotherapy study." Epilepsia 49 (2007): 438-45

4. McGuire JM, Baram V, Asher JM "Osteopenia Associated With Divalproex Sodium." J Clin Psychopharmacol 24 (2004): 357-358

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