Psychiatric Bulletin (2000) 24: 395. doi: 10.1192/pb.24.10.395
© 2000 The Royal College of Psychiatrists
This Article
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Armour, D.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Armour, D.
Psychiatric Bulletin (2000) 24: 395
© 2000 The Royal College of Psychiatrists

Correspondence

Prescribing and monitoring of valproate

David Armour, Senior Pharmacist

Pharmacy Department, Springfield University Hospital, 61 Glenburnie Road, London SW17 7DJ

Sir: The authors of a recent paper (Taylor et al, 2000) have drawn much-needed attention to the high prevalence of subtherapeutic treatment of conditions such as mood disorders with carbamazepine or valproate. However, the authors have given much emphasis to the use of drug serum levels in monitoring the use of both these drugs in such conditions.

Personal experience suggests that there are potential pitfalls for the unwary in the interpretation of valproate levels. In particular, in a minority of patients it may be impossible to reach the stated trough threshold level of 50 mg/l, even at daily doses in excess of the licensed maximum and despite supervised compliance.

One possible reason for this is that valproate is highly (about 90%) bound to plasma protein at low body levels, but with increasing doses the binding sites become saturated and free levels rise. More active drug is thereby delivered to the central nervous system (CNS) (Dollery, 1991) without in some cases more than a marginal rise in measured (bound plus unbound) serum levels. This effect should be borne in mind if measured levels do not rise in proportion to a dose increase in a particular case.

Other factors confounding the interpretation of valproate levels include the fact that: the effects in the CNS considerably outlive the detectable presence of the drug in the body, possibly because of active metabolites; there is variable displacement from serum binding sites by free fatty acids; blood samples taken just before a dose may not consistently represent trough levels, because of possible entero-hepatic recirculation and diurnal variation in elimination (Chapman et al, 1982; Dollery, 1991). These factors explain, at least in part, why valproate measurements tend to be unreliable for some clinical purposes.

References

  1. CHAPMAN, A., KEANE, P. E., MELDRUM, B. S., et al (1982) Mechanism of anticonvulsant action of valproate. Progress in Neurobiology, 19, 315-359.[CrossRef][Medline]
  2. DOLLERY, C. (ed.) (1991) Therapeutic Drugs. Vol. 2: Sodium Valproate. Edinburgh: Churchill Livingstone.
  3. TAYLOR, D. M., STARKEY, K. & GINARY, S. (2000) Prescribing and monitoring of carbamazepine and valproate — a case note review. Psychiatric Bulletin, 24, 174-177.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Psychiatr. Bull.Home page
E. Day and J. Bolton
The Collegiate Trainees' Committee
Psychiatr. Bull., January 1, 2002; 26(1): 22 - 23.
[Full Text] [PDF]

This Article
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Armour, D.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Armour, D.