Summary
The study was designed to investigate the antimanic profile of carbamazepine as a first-line drug in affective or schizoaffective disorders, to correlate the clinical efficacy with the plasma level of carbamazepine and its 10,11-epoxide metabolite, and to test the potential value of monitoring the salivary level. It was administered alone for 3 weeks to 21 acute manic inpatients. During the first week, the dosage was rapidly increased to 800 mg/day in order to produce steady-state plasma levels of carbamazepine on Day 7. The individual dose was then adjusted to maintain the therapeutic range of 8–12 mg/l. Plasma and saliva levels of the drug and its metabolite, as well as clinical status were assessed weekly.
Overall, there was 62% globally improved patients and 77% in affective disorders. The improvement of manic symptoms was significantly lower in schizoaffective than in affective disorders, whereas the dropout rate and the need for antipsychotic medication was higher in the former group.
The antimanic response was significantly correlated with the plasma levels both of carbamazepine and its epoxide metabolite, with a time-lag consistent with a delayed drug effect.
Drug and metabolite concentrations in saliva were close to their plasma free fraction and were strongly correlated with their plasma levels, suggesting the potential value of salivary drug monitoring.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Albright PS, Bruni J (1984) Effects of carbamazepine and its epoxide metabolite on amygdala-kindled seizures in rats. Neurology 34: 1383–1386
Alric R, Arce-Corrales L, Blayac JP, Puech R (1984) Statistical analysis of performance of a liquid chromatographic assay of anticonvulsants involving solvent-demixing extraction and reciprocal internal standardization. Meth Find Exptl Clin Pharmacol 6: 353–361
Azorin JM, Pupeschi G, Bottai T, Pringuey D (1988) Plasma concentration of carbamazepine and its 10,11-epoxide metabolite in manic patients. Psychopharmacology 96 [Suppl]: 288
Azorin JM, Samuelian JC, Pringuey D, Donnet A, Bottai T, Dufour H, Tatossian A (1986) Place de la carbamazepine dans le traitement des psychoses endogènes. Résultats d'une étude ouverte. L'Encéphale 12: 115–119
Ballenger JC (1988) The clinical use of carbamazepine in affective disorders. J Clin Psychiat 49 [Suppl]: 13–19
Ballenger JC, Post RM (1978) Therapeutic effects of carbamazepine in affective illness — a preliminary report. Commun Psychopharmacol 2: 159–175
Ballenger JC, Post RM (1980) Carbamazepine in manic depressive illness: a new treatment. Am J Psychiat 137: 782–790
Bech P, Bolwig TG, Kramp P, Rafaelsen OJ (1979) The Bech-Rafaelsen Mania Scale and the Hamilton Depression Scale. Evaluation of homogeneity and inter-observer reliability. Acta Psychiat Scand 59: 420–430
Brown D, Silverstone T, Cookson JC (1989) Carbamazepine compared to haloperidol in acute mania. Int Clin Psychopharmacol 4: 229–238
Choonara IA, Rane A (1990) Therapeutic drug monitoring of anti-convulsants. State of the art. Clin Pharmacokinet 18: 318–328
Cookson JC (1988) La carbamazepine dans la psychose maniacodépressive. Psychol Méd 20: 1549–1561
Frigerio A, Morselli PL (1975) Carbamazepine: biotransformation. In: Penry JK, Daly DD (eds) Adv Neurol, Elsevier, New York, pp 295–308
Grossi E, Sacchetti E, Vita A, Conte G, Faravelli C, Hautman G, Zerbi D, Mesina AM, Drago F, Motta A (1984) Carbamazepine vs. chlorpromazine in mania: a double-blind trial. In: Emrich MH, Okuma T, Müller AA (eds) Anticonvulsants in affective disorders. Excerpta Medica, Amsterdam, pp 177–187
Guelfi JD, Pull CB, Guelfi C, Ruschel S, Dreyfus JF (1983) La CHESS-Utilisation dans la pathologie anxieuse et dépressive. Structure factorielle. Ann Méd-Psychol 141: 257–278
Klein E, Bental E, Lerer B, Belmaker RH (1984) Carbamazepine and haloperidol v placebo and haloperidol in excited psychosis. Arch Gen Psychiat 41: 165–170
McAuliffe JJ, Sherwin AL, Leppik IE, Fayle SA, Pippenger CE (1977) Salivary levels of anticonvulsants: a practical approach to drug monitoring, Neurology 27: 409–413
McKichan JJ, Duffner PK, Cohen ME (1981) Salivary concentrations and plasma protein binding of carbamazepine and carbamazepine 10,11-epoxide in epileptic patients. Br J Clin Pharmacol 12: 31–37
Okuma T, Inanaga K, Otsuki S, Sarai K, Takahashi R, Hazama H, Mori A, Watanabe S (1979) Comparison of the antimanic efficacy of carbamazepine and chlorpromazine. A double-blind controlled study. Psychopharmacol 66: 211–217
Okuma T, Kichimoto A, Inoue K (1973) Antimanic and prophylactic effects of carbamazepine (Tegretol) on manic depressive psychosis. A preliminary report. Folia Psychiat Neurol Jpn 27: 283–297
Okuma T, Tamashita I, Takahashi R, Itoh H, Kurihara M, Otsuki S, Watanabe S, Sarai K, Hazama H, Inanaga K (1989) Clinical efficacy of carbamazepine in affective, schizoaffective, and schizophrenic disorders. Pharmacopsychiat 22: 47–53
Pichot P, Overall JE, Gorham DR (1967) Echelle abrégée d'appréciation psychiatrique. Centre de Psychologie Appliquée (ed), Paris
Placidi GF, Lenzi A, Lazzerini F, Cassano GB, Akiskal HS (1986) The comparative efficacy and safety of carbamazepine versus lithium: a randomized, double-blind 3-year trial in 83 patients. J Clin Psychiat 47: 490–494
Post RM, Uhde TW, Ballenger JC (1984a) Efficacy of carbamazepine in affective disorders: Implications for underlying physiological and biochemical substrates. In: Emrich HM, Okuma T, Muller AA (eds) Anticonvulsants in affective disorders. Elsevier, Amsterdam, pp 93–115
Post RM, Uhde TW, Ballenger JC, Chatterji DC, Greene RF, Bunney WE (1983) Carbamazepine and its 10,11-epoxide metabolite in plasma and CSF. Relationship to antidepressant response. Arch Gen Psychiat 40: 673–676
Post RM, Uhde TW, Wolff EA (1984b) Profile of clinical efficacy and side effects of carbamazepine in psychiatric illness: Relationship to blood and CSF levels of carbamazepine and its 10,11-epoxide metabolite. Acta Psychiat Scand 69: 104–120
Ramsay RE, McManus DQ, Guterman A, Briggle TV, Vazquez D, Perchalski R, Yost RA, Wong P (1990) Carbamazepine metabolism in humans: effect of concurrent anticonvulsant therapy. Ther Drug Monit 12: 235–241
Rylance GW, Moreland TA (1981) Saliva carbamazepine and phenytoin level monitoring. Arch Dis Child 56: 637–652
Sillanpää M (1981) Carbamazepine pharmacology and clinical uses. Acta Neurol Scand 64 [Suppl 88]: 145–163
Stoll KD, Bisson HE, Fischer E, Gommel G, Goncalves N, Kröber HL, Nadler A, Troyke P (1985) Carbamazepine versus haloperidol in manic syndromes — First report of a multicentre study in Germany. In: Shagass C, Josiassen RC, Bridger WH, Weiss KJ, Stoff D, Simpson GM (eds) Biological Psychiatry. Elsevier, Amsterdam, pp 332–334
Tomson T, Bertilsson L (1984) Potent therapeutic effect of carbamazepine-10,11-epoxide in trigeminal neuralgia. Arch Neurol 41: 598–601
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Petit, P., Lonjon, R., Cociglio, M. et al. Carbamazepine and its 10,11-epoxide metabolite in acute mania: clinical and pharmacokinetic correlates. Eur J Clin Pharmacol 41, 541–546 (1991). https://doi.org/10.1007/BF00314982
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00314982