Mood Stabilizers as Medications divalproex, Depakote
Mood stabilizer: divalproex, Depakote
Generic Name: divalproex
Brand Name(s): Depakote
Common Use: Mood stabilizer
Divalproex sodium has anticonvulsant properties, and is chemically related
to valproic acid. Although its mechanism of action has not yet been established,
it has been suggested that its activity is related to increased brain levels
of gamma-aminobutyric acid (GABA). The effect on the neuronal membrane is
unknown. It dissociates into valproic acid in the gastrointestinal tract.
Divalproex is indicated in the treatment of the manic episodes associated
with bipolar disorder (DSM-III-R). The effectiveness of divalproex in long-term
use, that is for more than 3 weeks, has not been systematically evaluated
in controlled trials. Dilvalproex is not indicated for use as a mood stabilizer
in patients under 18 years of age.
Patients with hepatic disease or significant dysfunction. Hypersensitivity
to the drug.
Adverse Side Effects
Nausea, vomiting and indigestion are the most commonly reported side effects
at the initiation of therapy. These effects are usually transient and rarely
require discontinuation of therapy. Diarrhea, abdominal cramps and constipation
have also been reported. Anorexia with some weight loss and increased appetite
with some weight gain have also been seen.
Sedative effects have been noted in patients receiving valproic acid alone
but are found most often in patients on combination therapy. Sedation usually
disappears upon reduction of other antiepileptic medication. Ataxia, headache,
nystagmus, diplopia, asterixis, "spots before the eyes", tremor (may be dose-related),
dysarthria, dizziness, and incoordination have rarely been noted. Rare cases
of coma have been reported in patients receiving valproic acid alone or in
conjunction with phenobarbital.
Transient increases in hair loss have been observed. Skin rash, photosensitivity,
generalized pruritus, erythema multiforms, Stevens-Johnson syndrome and petechiae
have rarely been noted.
There have been reports of irregular menses and secondary amenorrhea, breast
enlargement, galactorrhea and parotid gland swelling in patients receiving
valproic acid. Abnormal thyroid function tests have been reported (see Precautions).
Emotional upset, depression, psychosis, aggression, hyperactivity and behavioral
deterioration have been reported.
Weakness has been reported.
Hearing loss, either reversible or irreversible, has been reported however,
a cause and effect relationship has not been established.
Edema of extremities has been reported.
The incidence of adverse events has been ascertained based on data from 2
short-term (21 day) placebo-controlled clinical trials of divalproex in the
treatment of acute mania, and from 2 long-term (up to 3 years) retrospective
Most Commonly Observed:
During the short-term placebo-controlled trials, the 6 most commonly reported
adverse events in patients (N=89) exposed to divalproex were nausea (22%),
headache (21%), somnolence (19%), pain (15%), vomiting (12%), and dizziness
In the long-term retrospective trials (634 patients exposed to divalproex),
the 6 most commonly reported adverse events were somnolence (31%), tremor
(29%), headache (24%), asthenia (23%), diarrhea (22%) and nausea (20%).
Associated With Discontinuation of Treatment:
In the placebo-controlled trials, adverse events which resulted in valproate
discontinuation in at least 1% of patients were nausea (4%) abdominal pain
(3%), somnolence (2%) and rash (2%). In the long-term retrospective trials,
adverse events which resulted in valproate discontinuation in at least 1%
of patients were alopecia (2.4%), somnolence (1.9%), nausea (1.7%) and tremor
(1.4%). The time to onset of these events was generally within the first 2
months of initial exposure to valproate. A notable exception was alopecia,
which was first experienced after 3 to 6 months of exposure by 8 of the 15
patients who discontinued valproate in response to the event.
Naloxone has been reported to reverse the CNS depressant effects
of valproic acid overdosage. Because naloxone could theoretically also reverse
the antiepileptic effects of divalproex, it should be used with caution in
patients with epilepsy.
Since divalproex tablets are enteric-coated, the benefit of gastric ravage
or emesis will vary with the time since ingestion. General supportive measures
should be applied with particular attention to the prevention of hypovolemia
and the maintenance of adequate urinary output.
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