Valproate for Acute Mania: Is Practice Really Evidence-Based and Recommended?
Authors from the University of Western Ontario conducted an audit in an acute psychiatric intake unit to determine whether the prescription of valproate there corresponded to evidence-based recommendations.
Valproate in the Treatment of Mania in Bipolar Disorder
Valproate is an alternative to lithium or atypical antipsychotics for patients with manic episodes of bipolar disorder. It is particularly recommended if the patient has already experienced multiple episodes of mania, tends to be more irritable and dysphoric, and simultaneously abuses a substance or has a history of head injury. For hospitalized patients, a rapid initial dose of valproate, 20–30 mg/kg body weight, is recommended as it usually yields a quicker effect than gradual titration from a lower starting dose. Once the therapeutic concentration is achieved, the daily dose is reduced.
The authors of the presented work were also interested in the prescribed forms of valproate and whether the drug was administered in a rapid dosage scheme.
Evaluated Data
Data from 43 patients (58% women) admitted to the hospital for acute mania and subsequently discharged with valproate as the set medication were evaluated. Recorded information included drug form, patient weight (necessary for dose calculation in accelerated dosing), initial valproate dose and its gradual adjustment, monitoring of serum valproate concentrations, and other prescribed psychopharmaceuticals.
Audit Findings
The majority (95%) of patients received sodium valproate (natrii valproas), and the remaining patients received divalproex (valproate semisodium – a stable complex formed by valproic acid and sodium valproate; currently not available in the Czech Republic). Except for one patient, all patients received a combination of antipsychotics. Weight was recorded for only 4 patients (9%).
The average daily dose of valproate after the first week of use was 1027 mg. The time required to reach the maximum daily dose (1426 mg) from the initial dose averaged 29 days. Serum valproate concentrations were monitored in 34 cases (79%), although the average time between the initial dose of valproate and the first measurement of serum concentrations was 38 days. A significant positive correlation was found between the number of days needed to reach the maximum dose and the length of hospitalization (Spearman's rank correlation coefficient ρ = 0.41; n = 43; p = 0.006).
Practical Implications
Rapid valproate dosing was not a common practice at this Canadian center, which could have resulted in suboptimal treatment efficacy, likely leading to the use of a combination of antipsychotics. The study highlights the importance of adequate initial valproate dosing in the treatment of manic patients and points out that practice in this case was not entirely evidence-based.
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Sources:
- Vasudev K., Mead A., Macritchie K., Young A. H. Valproate in acute mania: is our practice evidence based? Int J Health Care Qual Assur 2012; 25 (1): 41–52, doi: 10.1108/09526861211192395.
- Shah N., Grover S., Rao G. P. Clinical practice guidelines for management of bipolar disorder. Indian J Psychiatry 2017; 59 (Suppl. 1): S51–S66, doi: 10.4103/0019-5545.196974.
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