Divalproex

Using chaos theory to explain how divalproex treats bipolar disorder

Client:
Sanofi-Synthelabo
Category:
Central nervous system

Cutting-edge science and differentiation

Initial probes of the data reveal a pharmacology for divalproex that is quite distinct to that of monomeric valproate. Unexpected and previously-unknown relationships are interpreted by McCormack to suggest a concentration-dependent potential of divalproex to self-assemble. Subsequently, space-filling modeling of divalproex in solution provided dramatic visualization of the self-assembling character of divalproex. This novel behaviour could not be modeled for other formulations of valproate.

Clinical implications of new teachings

Further modeling showed how aggregates of divalproex, by comparison with monomeric valproate, are able to more efficiently modify the aberrant neuronal signaling of bipolar disorder through covalent interactions with membrane phospholipids. Importantly, these outcomes provided prescribers with new teachings that by supporting the clinical findings, justified the selective licensed use of divalproex in the management of bipolar disorder, while reducing plagiarism of sales through unlicensed use of monomeric formulations of valproic acid.

Female doctor talks to her female patient who is facing away from us
© Shutterstock

Key outcomes

  • Expansion of use within an approved indication

Formal presentations of new teachings by Keith McCormack

  • A new mathematics in medicine. Is Depakote evidence in support of a new order of self-organising therapeutic systems? Bipolar Affective Disorder (Satellite meeting on first day) 27th-28th November 2001, Institute of Psychiatry, London.
  • Depakote the dimer vs valproate the monomer: A New Perspective in Bipolar Disorder Treatment. A UK Sanofi-Synthelabo-sponsored tour 22nd-26th April 2002.
  • The role of valproate semi-sodium (Depakote) in the management of bipolar disorder. Royal College of Gynaecology, London 10th May 2002.
  • A new mathematics in medicine. Is Depakote evidence in support of a new order of self-organising therapeutic systems? The Second Annual Institute of Psychiatry 'Matter-to-Mind' Symposium, 'Bipolar Affective Disorder, From Matter to Mind', (Main program) 27th-28th November 2001, Institute of Psychiatry, London.
  • Lecture Tour (UK). 'Pole 2 Pole' 2002. Depakote the dimer vs valproate the monomer: A new perspective in Bipolar Disorder treatment. Sponsored by Sanofi-Synthelabo (UK). Leeds, Manchester, Sheffield, Birmingham, Worcester, London. 22nd to 24th April 2002.
  • What is valproate semi-sodium? Roundtable Meeting sponsored by Sanofi-Synthelabo (UK); The role of valproate semi-sodium (Depakote) in the management of bipolar disorder. 10th May 2002, Royal College of Gynaecology, London.