Background: In patients suffering from bipolar disorders (BPD), we explored to what extent oral loading of sodium valproate (SV) leads to more rapid symptom improvement compared to intravenous loading and oral maintenance administration. Methods: Ninety patients (mean age: 35.00 years) with BPD and currently in an acute manic state were randomly assigned to one of three study conditions: oral loading (20 mg/kg oral single-dose SV on the first day, then 10-15 mg/kg SV daily, divided dose), intravenous loading (20 mg/kg SV intravenous injection on the first day, then 10-15 mg/kg orally, divided dose), or oral maintenance administration (15-20 mg/kg SV daily from the beginning) over the first 7 days of treatment. SV plasma levels, side effects and symptoms were evaluated at baseline and on days 1, 3, and 7 after commencing treatment. Results: There were significant Time-by-Group interactions for symptom improvements, symptom severity, and SV plasma levels, with positive values in the oral and intravenous loading conditions, compared to the oral maintenance condition. Post hoc analyses showed that oral and intravenous conditions led to similar improvements. Conclusions: Both oral and intravenous loading of SV led to quicker and more efficient improvement and SV plasma levels as compared to an oral maintenance regimen.

Sanches M, Newberg AR, Soares JC: Emerging drugs for bipolar disorder. Expert Opin Emerg Drugs 2000;15:453-466.
Perlis RH, Ostacher MJ, Patel JK, Marangell LB, Zhang H, Wisniewski SR, Ketter, TA, Miklowitz DJ, Otto MW, Gyulai L, Reilly-Harrington NA, Nierenberg AA, Sachs GS, Thase ME: Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry 2006;163:217-124.
Kilbane EJ, Gokbayrak NS, Galynker I, Cohen L, Tross S: A review of panic and suicide in bipolar disorder: does comorbidity increase risk? J Affect Disord 2009;115:1-10.
Gardner HH, Kleinman NL, Brook RA, Rajagopalan K, Brizee TJ, Smeeding JE: The economic impact of bipolar disorder in an employed population from an employer perspective. J Clin Psychiatry 2006;67:1209-1218.
Cipriani A, Reid K, Young AH, Macritchie K, Geddes J: Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder. Cochrane Database Syst Rev 2013;10:CD003196.
Oluboka OJ, Bird DC, Kutcher S, Kusumakar V: A pilot study of loading versus titration of valproate in the treatment of acute mania. Bipolar Disord 2002;4:341-345.
Hirschfeld RM, Allen MH, McEvoy JP, Keck PE Jr, Russell JM: Safety and tolerability of oral loading divalproex sodium in acutely manic bipolar patients. J Clin Psychiatry 1999;60:815-818.
Grunze H, Erfurth A, Amann B, Giupponi G, Kammerer C, Walden J: Intravenous valproate loading in acutely manic and depressed bipolar I patients. J Clin Psychopharmacol 1999;19:303-309.
Bowden CL, Swann AC, Calabrese JR, Rubenfaer LM, Wozniak PJ, Collins MA, Abi-Saab W, Saltarelli M; Depakote ER Mania Study Group: A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the treatment of acute mania. J Clin Psychiatry 2006;67:1501-1510.
Bond DJ, Lam RW, Yatham LN: Divalproex sodium versus placebo in the treatment of acute bipolar depression: a systematic review and meta-analysis. J Affect Disord 2010;124:228-234.
Smith LA, Cornelius VR, Azorin JM, Perugi G, Vieta E, Young AH, Bowden CL: Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis. J Affect Disord 2010;122:1-9.
Moog C, Kuntz-Simon G, Caussin-Schwemling C, Obert G: Sodium valproate, an anticonvulsant drug, stimulates human immunodeficiency virus type 1 replication independently of glutathione levels. J Gen Virol 1996;77:1993-1999.
Macritchie K, Geddes JR, Scott J, Haslam D, de Lima M, Goodwin G: Valproate for acute mood episodes in bipolar disorder. Cochrane Database Syst Rev 2003;10:CD004052.
Kamalinia G, Brand S, Ghaeli P, Abedi N, Bajoghli H, Sharifi V, Zahiroddin A, Amini M, Rouini MR, Holsboer-Trachsler E, Mohammadpoor AH: Serum levels of sodium valproate in patients suffering from bipolar disorders: comparing acute and maintenance phases of mania. Pharmacopsychiatry 2013;46:83-87.
Lennkh C, Simhandl C: Current aspects of valproate in bipolar disorder. Int Clin Psychopharmacol 2000;15:1-11.
Pope HG Jr, McElroy SL, Keck PE Jr, Hudson JI: Valproate in the treatment of acute mania. A placebo-controlled study. Arch Gen Psychiatry 1991;48:62-68.
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC: The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(suppl 20):22-33.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4, text revision (DSM-IV-TR). Washington, American Psychiatric Association, 2000.
Young RC, Biggs JT, Ziegler VE, Meyer DA: A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 1978;133:429-435.
Guy W: ECDEU Assessment Manual for Psychopharmacology, revised ed. Rockville, NIMH, 1976.
Machado-Vieira R, Soares JC, Lara DR, Luckenbaugh DA, Busnello JV, Marca G, Cunha A, Souza DO, Zarate CA Jr, Kapczinski FA: Double-blind, randomized, placebo-controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania. J Clin Psychiatry 2008;69:1237-1245.
De Berardis D, Conti CM, Campanella D, Carano A, Di Giuseppe B, Valchera A, Tancredi L, Serroni N, Pizzorno AM, Fulcheri M, Gambi F, Sepede G, Moschetta FS, Salerno RM, Ferro FM: Evaluation of plasma antioxidant levels during different phases of illness in adult patients with bipolar disorder. J Biol Regul Homeost Agents 2000;22:195-200.
Plante DT, Winkelman JW: Sleep disturbance in bipolar disorder: therapeutic implications. Am J Psychiatry 2008;165:830-843.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.