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Chapter 29: Psychopharmacological Treatment
The plasma concentrations of carbamazepine, diazepam
(Valium), amitriptyline (Elavil), nortriptyline (Pamelor), and
phenobarbital (Luminal) may also be increased when these
drugs are coadministered with valproate, and the plasma con-
centrations of phenytoin (Dilantin) and desipramine (Nor-
pramin) may be decreased when they are combined with
valproate. The plasma concentrations of valproate may be
decreased when the drug is coadministered with carbamaze-
pine and may be increased when coadministered with guanfa-
cine (Tenex), amitriptyline, or fluoxetine (Prozac). Valproate
can be displaced from plasma proteins by carbamazepine,
diazepam, and aspirin. Persons who are treated with anticoag-
ulants (e.g., aspirin and warfarin [Coumadin]) should also be
monitored when valproate use is initiated to assess the devel-
opment of any undesired augmentation of the anticoagulation
effects. Interactions of valproate with other drugs are listed in
Table 29.33-3.
Laboratory Interferences
Valproate may cause laboratory increase of serum-free fatty
acids. Valproate metabolites may produce a false-positive test
result for urinary ketones as well as falsely abnormal thyroid
function test results.
Dosage and Clinical Guidelines
When starting valproate therapy, a baseline hepatic panel, CBC
and platelet counts, and pregnancy testing should be ordered.
Additional testing should include amylase and coagulation stud-
ies if baseline pancreatic disease or coagulopathy is suspected.
In addition to baseline laboratory tests, hepatic transaminase
concentrations should be obtained 1 month after initiation of
therapy and every 6 to 24 months thereafter. However, because
even frequent monitoring may not predict serious organ toxicity,
it is more prudent to reinforce the need for prompt evaluation
of any illnesses when reviewing the instructions with patients.
Asymptomatic elevation of transaminase concentrations up to
three times the upper limit of normal are common and do not
require any change in dosage. Table 29.33-4 lists the recom-
mended laboratory tests for valproate treatment.
Valproate is available in a number of formulations
(Table 29.33-5). For treatment of acute mania, an oral loading
Table 29.33-3
Interactions of Valproate with Other Drugs
Drug
Interactions Reported with Valproate
Lithium
Increased tremor
Antipsychotics
Increased sedation; increased
extrapyramidal effects; delirium and
stupor (single report)
Clozapine
Increased sedation; confusional
syndrome (single report)
Carbamazepine
Acute psychosis (single report); ataxia,
nausea, lethargy (single report);
may decrease valproate serum
concentrations
Antidepressants
Amitriptyline and fluoxetine
may increase valproate serum
concentrations
Diazepam
Serum concentration increased by
valproate
Clonazepam
Absence status (rare; reported only in
patients with pre-existing epilepsy)
Phenytoin
Serum concentration decreased by
valproate
Phenobarbital
Serum concentration increased by
valproate; increased sedation
Other CNS depressants Increased sedation
Anticoagulants
Possible potentiation of effect
CNS, central nervous system.
Table 29.33-4
Recommended Laboratory Tests
During Valproate Therapy
Before Treatment
Standard chemistry screen with special attention to liver
function tests
CBC, including WBC and platelet count
During Treatment
Liver function tests at 1 month; then every 6–24 months if no
abnormalities are found.
Complete blood work with platelet count at 1 month; then
every 6–24 months if findings are normal.
If Liver Function Test Results Become Abnormal
Mild transaminase elevation (less than three times normal):
monitoring every 1–2 weeks; if stable and patient is responding
to valproate, results are monitored monthly to every 3 months.
Pronounced transaminase elevation (more than three times
normal): dosage reduction or discontinuation of valproate;
increase dose or rechallenge if transaminases normalize and
if the patient is a valproate responder.
CBC, complete blood count; WBC, white blood cell.
Table 29.33-5
Valproate Preparations Available in the United States
Generic Name
Trade Name, Form (Doses)
Time to Peak
Valproate sodium injection Depacon injection
(100 mg valproic acid/mL)
1 hr
Valproic acid
Depakene, syrup (250 mg/5 mL)
1–2 hr
Depakene, capsules (250 mg)
1–2 hr
Divalproex sodium
Depakote, delayed-released
tablets (125, 250, 500 mg)
3–8 hr
Divalproex sodium-coated
particles in capsules
Depakote, sprinkle capsules
(125 mg)
Compared with divalproex tablets, divalproex sprinkle has earlier
onset and slower absorption, with slightly lower peak plasma
concentration.
