One was a 1997 study that compared maintenance with a combination of lithium and divalproex
with lithium and placebo.
In a retrospective study, Henry et al (6) found that cotherapy with lithium but not divalproex
or carbamazepine protects against antidepressant-induced mania, and that switch rates to mania were the same whether or not an antidepressant was taken with an anticonvulsant.
Among anticonvulsants, divalproex
and valproate sodium have good evidence of efficacy.
The 153 outpatients age 7 to 17 in a bipolar I manic or mixed episode were randomly assigned to lithium, divalproex
, or placebo for 8 weeks.
Complicating the matter is the trend away from treatment with lithium and divalproex
sodium (Depakote), towards newer anticonvulsants and atypical antipsychotics.
FIGURE 1 Current approved and unapproved agents for bipolar disorder Acute Mania Acute Depression Maintenance Year Drug Year Drug Year Drug 1970 Lithium 2003 Olanzapine/fluoxetine 1974 Lithium combination 1973 Chlorpromazine 2006 Quetiapine 2003 Lamotrigine 1994 Divalproex
2004 Olanzapine 2000 Olanzapine (1) 2005 Aripiprazole 2003 Risperidone (1) 2008 Quetiapine (Adj.) 2004 Quetiapine (1) 2009 Risperidone LAI 2004 Ziprasidone Unmet need 2004 Aripiprazole 2004 Carbamazepine Unmet need 2005 Divalproex
ER 2009 Asenapine Adapted from Ketter TA, ed.
Baker, medical director of the Copper Ridge Institute in Sykesville, Md., reported on a small study of divalproex
, a mood-stabilizing anticonvulsant that is effective in treating aggression in brain-injured patients, regardless of the nature of the injury and of the presence or absence of EEG abnormalities.
C is compliant with her medications, which include lithium, 450 mg bid, divalproex
ER, 1,500 mg/d, and sertraline, 150 mg each morning.
For patients with attacks at all times of the day, choices include methysergide, verapamil, and divalproex
. Lithium carbonate is also an option, although it carries a risk of several drug-drug interactions that restrict its use to select patients, he said.