A pilot study of loading versus titration of valproate in the treatment of acute mania
ABSTRACT This double-blind pilot study compares the effectiveness and incidence of adverse effects of oral loading versus titration schedules of valproate in acute mania.
Consecutive new admissions for an acute manic episode were prescribed either an oral loading dose (20 mg/kg/day; n = 5; mean age = 33.4) or slower titration dose (10 mg/kg/day, n = 6. mean age = 30.6) of valproate for 7 days without other psychotropic agents. with the exception of benzodiazepines. Daily outcome measures included: serum valproic acid levels, the Young Mania Rating Scale (YMRS), the Brief Psychiatry Rating Scale (BPRS), the Clinical Global Impression Scale (CGI) and the Adverse Effect Rating Scale.
The mean serum valproic acid levels were significantly higher in the loading group when compared with the titration group after 1 and 2 days following the initiation of treatment (p < 0.05). After 3 days of treatment there was a trend for the group that received the loading regimen to have slightly more improvement in YMRS scores compared with the titration group. Side-effects were minor for both treatments, however, a higher incidence of side-effects was reported in the titration group, with 50% of patients reporting sedation most likely because of increased use of benzodiazepines.
This suggests that a loading dose of valproate is likely safe and may provide an earlier onset of antimanic effects in patients with bipolar disorder. Future studies with larger sample sizes are indicated.
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Article: Treatment of Acute Mania[Show abstract] [Hide abstract]
ABSTRACT: Mood stabilizers have evolved considerably over the past decade. Lithium, divalproex, and olanzapine are currently Food and Drug Administration-approved for the treatment of acute mania. A number of new and traditional medications have also been tested and are commonly used in clinical practice. Several strategies for managing treatment-resistant mania have been suggested, but few have been rigorously tested. Emphases on rapid stabilization and fewer side effects have raised the bar for what is expected from mood stabilizers and the successful treatment of mania involves a delicate balance between swiftness, short-term tolerability, and long-term safety.CNS spectrums 01/2004; 8(12):917-20, 924-8. · 2.71 Impact Factor
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ABSTRACT: To describe the evidence for the efficacy and tolerability of valproate in treatment of bipolar disorders, as well as factors associated with favorable or unfavorable outcomes. Studies published from 2000 onwards were reviewed, as well as published abstracts. For clinical trials, randomized, prospective studies were emphasized. Several mechanisms of action of valproate on central nervous system neurons that may be relevant to its actions in bipolar disorders have been recently reported. These include inhibition of glycogen synthase kinase and activation of extracellular signal-regulated kinase. Several of the actions overlap those observed from lithium. Valproate is effective in treatment of mania, and somewhat more effective in certain patient subgroups than other treatments, e.g. mixed mania, and mania with prominent irritability. Valproate is comparable with olanzapine in maintenance treatment, and somewhat better tolerated. Higher serum levels, particularly above 110 microg/ml, are associated with more reports of weight gain, sedation, and reductions in platelet count. Valproate may be associated with an increased rate of polycystic ovarian syndrome, with increased weight contributing to the risk. Valproate reduces total cholesterol levels, particularly among patients with baseline elevations of cholesterol. Several studies indicate that valproate can be beneficially combined with antipsychotic drugs and other treatments for bipolar disorder. Valproate continues to be studied in further clarification of its mechanisms, efficacy, risks, and spectrum of benefits in bipolar disorder. It is a major treatment for bipolar disorder, both in monotherapy and combination therapy regimens.Acta psychiatrica Scandinavica. Supplementum 02/2005; 111(426):13-20. DOI:10.1111/j.1600-0447.2005.00522.x