Kaplan + Sadock's Synopsis of Psychiatry, 11e

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Chapter 29: Psychopharmacological Treatment

Table 29.33-3 Interactions of Valproate with Other Drugs

Table 29.33-4 Recommended Laboratory Tests During Valproate Therapy

Drug

Interactions Reported with Valproate

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 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.

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 Amitriptyline and fluoxetine may increase valproate serum concentrations Serum concentration increased by valproate Absence status (rare; reported only in patients with pre-existing epilepsy) Serum concentration decreased by valproate Serum concentration increased by valproate; increased sedation

Antidepressants

Diazepam

Clonazepam

Phenytoin

Phenobarbital

Other CNS depressants Increased sedation Anticoagulants

Possible potentiation of effect

CNS, central nervous system.

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.

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

1 hr

(100 mg valproic acid/mL)

Valproic acid

Depakene, syrup (250 mg/5 mL) Depakene, capsules (250 mg) Depakote, delayed-released tablets (125, 250, 500 mg) Depakote, sprinkle capsules (125 mg)

1–2 hr 1–2 hr 3–8 hr

Divalproex sodium

Divalproex sodium-coated particles in capsules

Compared with divalproex tablets, divalproex sprinkle has earlier onset and slower absorption, with slightly lower peak plasma concentration.