Anticonvulsants have been successfully used in pharmacopsychiatry after their therapeutic
value in affective and schizoaffective disorders had been documented in several clinical
trials. As the authorities in several countries registered newer anticonvulsants with
fewer side effects, their therapeutic value in psychiatric disorders was studied.
Clinical studies from the early 80's onward have demonstrated the efficacy of oxcarbazepine
(OCBZ), a keto derivative of carbamazepine, in treating mania in affective and schizoaffective
disorders. In addition, OCBZ has a distinct pharmacokinetic profile concerning drug-drug
interactions compared to carbamazepine and other anticonvulsants. Therefore, the value
of OCBZ in the treatment of affective and schizoaffective disorders needs to be evaluated.
We reviewed the literature with regard to pharmacokinetic and pharmacodynamic characteristics
of OCBZ, drug-drug interactions relevant in pharmacopsychiatry, and the clinical effects
of OCBZ in the treatment of patients with affective and schizoaffective disorders.
According to the literature, OCBZ is regarded as effective in acute mania and appears
to reduce the dosage of neuroleptics required for the treatment of affective and schizoaffective
disorders. In addition, it has a preferable pharmacokinetic profile with less severe
side effects compared to carbamazepine and neuroleptics. Furthermore, since OCBZ does
not interact substantially with the cytochrome P450 enzyme system, co-administration
with neuroleptics or antidepressants appears to be well tolerated in affective disorders.
However, despite promising effects of OCBZ, few clinical studies have been published
in the last 15 years. We conclude that further studies should validate the efficacy
of OCBZ in treating mania and evaluate possible pharmacopsychiatric indications as
well as limitations for this psychotropic compound.
References
- 1
Äikiä M, Kälviäinen R, Sivenius J, Halonen T, Riekkinnen P J.
Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed epilepsy:
one year follow-up.
Epilepsy Research.
1992;
1
199-203
- 2 Aggleton J P, Mishkin M.
The amygdala: sensory gateway to the emotions. In: Plutchik R, Kellermann H (eds) Emotion: Theory, Research and Experience. Orlando;
Academic Press 1986
- 3
Anderman F, Schwabe S, McLean M J, Lloyd P, Baruzzi A.
Panel discussion: Part I.
Epilepsia.
1994;
35
(3)
S20
- 4
Ballenger J C, Post R M.
Carbamazepine in manic-depressive illness: a new treatment.
Am J Psychiatry.
1980;
137
782-790
- 5
Bech P, Bolwig T G, Kramp P, Rafaelson O J.
The Bech-Rafaelson Mania Scale and the Hamilton Depression Scale: evaluation of homogenity
and inter-observer reliability.
Acta Psychiatr Scand.
1979;
59
420-430
- 6
Beijamini V, Skalisz L L, Joca S R, Andreatini R.
The effect of oxcarbazepine of behavioural despair and learned helplessness.
Eur J Pharmacol.
1998;
347
(1)
23-27
- 7
Beran R G.
Cross-reactive skin eruption with both carbamazepine and oxcarbamazepine.
Epilepsia.
1993;
34
163-165
- 8
Bill P A, Vigonius U, Pohlmann A, Guerreiro C AM, Kochen S, Saffer D, Moore A.
A double-blind, controlled clinical trial of oxcarbazepine versus phenytoin in adults
with previously untreated epilepsy.
Epilepsy Research.
1997;
27
195-204
- 9
Borusiak P, Korn-Merker E, Holert N, Boenigk H E.
Hyponatremia induced by oxcarbazepine in children.
Epilepsy Res.
1998;
30
241-246
- 10
Bülau P, Paar W D, von Unruh G E.
Pharmacokinetics of oxcarbazepine and 10-hydroxy-carbazepine in the newborn child
of an oxcarbazepine-treated mother.
Eur J Clin Pharmacol.
1988;
34
311-313
- 11
Cabrera J F, Mühlbauer H D, Schley J, Stoll K D, Müller-Oerlinghausen B.
Long-term randomized clinical trial on oxcarbazepine vs. lithium in bipolar and schizoaffective
disorders: preliminary results.
Pharmacopsychiatry.
1986;
19
282-283
- 12
Cabrera J, Albrecht J, Müller-Oerlinghausen B.
Kombinierte rezidiv-prophylaktische Behandlung der manisch-depressiven Erkrankung
mit Lithium und Carbamazepin oder Oxcarbazepin.
Nervenarzt.
1987;
58
245-249
- 13
Curran H V, Java R.
Memory and psychomotor effects of oxcarbazepine in healthy human volunteers.
Eur J Clin Pharmacol.
1993;
44
529-533
- 14
Christe W, Krämer G, Vigonius U, Pohlmann H, Steinhoff B J, Martin J B, Martin J B,
Moore A.
A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate in
adults with newly diagnosed epilepsy.
Epilepsy Research.
1997;
26
451-460
- 15
Dam M.
Practical aspects of oxcarbazepine treatment.
Epilepsia.
1994;
35
(3)
S23-S25
- 16
Dam M, Ekberg R, Loyning Y, Waltimo O, Jakobsen K.
A double-blind study comparing oxcarbazepine and carbamazepine in patients with newly
diagnosed, previously untreated epilepsy.
Epilepsy Res.
1989;
3
70-76
- 17
Davis M.
The role of amygdala in fear-potentiated startle: implications for animal models of
anxiety.
Trends Pharmacol Sci.
1992;
13
35-41
- 18
Dickinson R G, Hooper W D, Dunstan P R, Eadie M J.
First dose and steady-state pharmacokinetics of oxcarbazepine in its 10-hydroxy metabolite.
Eur J Clin Pharmacol.
1989;
37
69-74
- 19
Dietrich D E, Emrich H M.
The use of anticonvulsants to augment antidepressant medication.
J Clin Psychiatry.
1998;
59
(5)
51-58
- 20
Dunn R T, Frye M S, Kimbrell T A, Denicoff K D, Leverich G S, Post R M.
The efficacy and use of anticonvulsants in mood disorders.
Clin Neuropharmacology.
1998;
21
215-235
- 21 Eadie M J, Tyrer J H.
Carbamazepine. In: Anticonvulsant therapy-pharmacological basis and practice, 3rd Ed. Oxford; Churchill
Livingstone 1989: 142-143
- 22
Emrich H M.
Studies with oxcarbazepine (Trileptal) in acute mania.
Intern Clin Psychopharmacol.
1990;
5
(1)
83-88
- 23 Emrich H M.
Experience with oxcarbazepine in acute mania. In: Modigh K, Robak OH, Vestergaard P (eds) Whrightson Biomedical Publishing 1994:
29-36
- 24
Emrich H M, von Zerssen D, Kissling W, Möller H J, Windorfer A.
Effect of sodium valproate in mania. The GABA-hypothesis of affective disorders.
Arch Psychiat Nervenkr.
1980;
229
1-16
- 25
Emrich H M, Altmann H, Dose M, von Zerssen D.
Therapeutic effects of GABA-ergic drugs in affective disorders - A preliminary report.
Pharmacol Biochem Behav.
1983;
19
369-372
- 26 Emrich H M, Dose M, von Zerssen D.
Action of sodium-valproate and of oxcarbazepine in patients with affective disorders. In: Emrich HM, Okuma T, Müller AA (eds) Anticonvulsants in affective disorders. Amsterdam;
Excerpta Medica 1984: 45-55
- 27
Emrich H M, Dose M, von Zerssen D.
The use of sodium valproate, carbamazepine and oxcarbazepine in patients with affective
disorders.
J Affect Disorders.
1985;
8
243-250
- 28
Emrich H M, Dose M, Wolf R.
The action of mood-stabilizers in affective disorders: an integrative view as a challenge.
Neuropsychobiology.
1993;
27
158-162
- 29 Fähndrich E.
Das AMDP-System. Manual zur Dokumentation psychiatrischer Befunde. Berlin; Springer 1981
- 30
Faigle J W, Menge G P.
Metabolic characteristics of oxcarbazepine (Trileptal) and their beneficial implications
for enzyme induction and drug interactions.
Behav Neurol.
1990;
3
(1)
21-30
- 31
Fattore C, Cipolla G, Gatti G, Limodo G L, Sturm Y, Bernasconi C, Perucca E.
Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy
women.
Epilepsia.
1999;
40
783-787
- 32
Friis M L, Kristensen O, Boas J, Dalby M, Deth S H, Gram L, Mikkelsen M, Pedersen B,
Sabers A, Worm-Pedersen J, Andersen D, Jensen P K.
Therapeutic experiences with 947 epileptic out-patients in oxcarbazepine treatment.
Acta Neurol Scand.
1993;
87
224-227
- 33
Garbutt J C, Loosen P T.
Is carbamazepine helpful in paroxysmal behavior disorder?.
Am J Psychiatry.
1983;
140
1363-1364
- 34
Garcia-Borreguero D, Raptis C, Weber M M, Dose M, Bremer D, Emrich H M.
Anticonvulsants as adjuncts for the neuroleptic treament of schizophrenic psychoses:
a clinical study with beclamide.
Acta Psychiat Scand.
1989;
81
162-167
- 35
Gatzonis S D, Georgaculias N, Singounas E, Jenkins A, Stamboulis E, Siafakas A.
Elimination of oxcarbazepine-induced oculogyric crisis following vagus nerve stimulation.
Neurology.
1999;
52
1918-1919
- 36
Grant S M, Faulds D.
Oxcarbazepine - A review of its pharmacology and therapeutic potential in epilepsy,
trigeminal neuralgia and affective disorders.
Drugs.
1992;
43
873-888
- 37
Greil W, Ludwig-Mayerhofer W, Erazo N, Schochlin C, Schmidt S, Engel R R, Czernik A,
Giedke H, Müller-Oerlinghausen B, Osterheider M, Rudolf G A, Sauer H, Tegeler J, Wetterling T.
Lithium versus carbamazepine in the maintenance treatment of bipolar disorders - a
randomized study.
J Affect Disord.
1997a;
43
151-161
- 38
Greil W, Ludwig-Mayerhofer W, Erazo N, Engel R R, Czernik A, Giedke H, Müller-Oerlinghausen B,
Osterheider M, Rudolf G A, Sauer H, Tegeler J, Wetterling T.
Lithium versus carbamazepine in the maintenance treatment of schizoaffective disorder
- a randomized study.
Eur Arch Psychiatry Clin Neurosci.
1997b;
247
42-50
- 39
Greil W, Kleindienst N, Erazo N, Müller-Oerlinghausen B.
Differential response to lithium and carbamazepine in the prophylaxis of bipolar disorder.
J Clin Psychopharmacol.
1998;
18
455-460
- 40 Hakaola H PA, Laulumaa V A.
Carbamazepine in violent schizophrenia. In: Emrich HM, Okuma T, Müller AA (eds) Anticonvulsants in affecive disorders. Amsterdam;
Exerpta Medica 1984: 204-207
- 41
Houtkooper M A, Lammertsma A, Meyer J W, Goedhart D M, Meinardi H, van Oorschot C A,
Blom G F, Hoppener R J, Hulsman J A.
Oxcarbazepine (GP 47.680): a possible alternative to carbamazepine?.
Epilepsia.
1987;
28
(6)
693-698
- 42
Isojarvi J I, Pakarinen A J, Myllyla V V.
Basic haematological parameters, serum gamma-glutamyl-transferase activity, and erythrocyte
folate and serum vitamin B 12 levels during carbamazepine and oxcarbazepine therapy.
Seizure.
1997;
6
207-211
- 43
Joca S R, Skalisz L L, Beijamini V, Vital M A, Andreatini R.
the antidepressive-like effect of oxcarbazepine: possible role of dopaminergic neurotransmission.
Eur Neuropsychopharmacol.
2000;
10
223-228
- 44
Kalinowsky L B, Putnam T J.
Attempts at treatment of schizophrenia and other nonepileptic psychoses with dilantin.
Arch Neurol Psychiatry.
1943;
49
414-420
- 45
Kidron R, Averbuch I, Klein E, Belmaker R H.
Carbamazepine induced reduction of blood levels of haloperidol in chronic schizophrenia.
Biol Psychiatry.
1985;
20
199-228
- 46
Klein E, Bental E, Lerer B, Belmaker H.
Carbamazepine and haloperidol vs. placebo and haloperidol in excited psychoses.
Arch Gen Psychiatry.
1984;
41
165-170
- 47
Klitgaard N A, Kristensen O.
Use of saliva for monitoring oxcarbazepine therapy in epileptic patients.
Eur J Clin Pharmacol.
1986;
31
91-94
- 48
Klosterskov-Jensen P, Saano V, Haring P, Svenstrup B, Menge G P.
Possible interaction between oxcarbazepine and an oral contraceptive.
Epilepsia.
1992;
33
1149-1152
- 49
Krämer G.
Oxcarbazepin (Trileptal®): Ein neues Antiepileptikum zur Mono- und Kombinationstherapie.
Akt Neurologie.
2000;
27
59-71
- 50
Krämer G, Bülau P, Blankenhorn V, Stoll K D.
Oxcarbazepin und Carbamazepin. Kinetik, Metabolismus, Enzyminduktion und Konsequenzen
für den klinischen Einsatz.
Münch Med Wschr.
1990;
132
(1)
S71-S74
- 51
Krämer G, Tettenborn B, Flesch G.
Oxcarbazepine-verapamil drug interaction in healthy volunteers.
Epilepsia.
1991;
32
(1)
70
- 52
Kristensen O, Klitgaard N A, Jönsson B, Sindrup S.
Pharmacokinetics of 10-OH-carbazepine, the main metabolite of the antiepileptic oxcarbazepine,
from serum and saliva concentrations.
Acta Neurol Scand.
1983;
68
145-150
- 53
Lambert P A, Carraz G, Borselli S, Carrel S.
Action neuropsychotrope d'un nouvel antiépileptique: Le Dépamide.
Ann Med Psychol.
1966;
1
707-710
- 54
Lambert P A, Carraz G, Borselli S, Bouchardy M.
Le dipropyl-acetamide dans le traitement de la psychose maniaco-depressive.
L'Encephale.
1975;
1
25-31
- 55
Leinonen E, Lepola U, Koponen H.
Substituting carbamazepine with oxcarbazepine increases citalopram levels. A report
on two cases.
Pharmacopsychiatry.
1996;
29
156-158
- 56 Litten R Z, Allen J P.
Pharmacological therapies of alcohol addiction. In: Miller NS, Gold MS (eds) Pharmacological therapies in drug and alcohol disorders. New
York; Marcel Dekker 1994: 127-141
- 57 Lorr M, Klett C, McNair D M, Lasky J J.
Inpatient Multidimensional Psychiatric Scale. Palo Alto/CA; Consulting Psychologists Press 1962
- 58
Macdonald R L, Kelly K M.
Antiepileptic drug mechanism of action.
Epilepsia.
1995;
36
(2)
S2-12
- 59
McElroy S L, Pope H G, Keck P E, et al.
Treatment of psychiatric disorders with valproate: a series of 73 cases.
Psychiatrie & Psychobiologie.
1988;
3
81-85
- 60
McElroy S L, Keck P E, Pope H G, et al.
Valproate in the treatment of bipolar disorders: literature review and clinical guidelines.
J Clin Psychopharmacol.
1992;
12
42S-52S
- 61
Monroe R R.
Limbic ictus and atypical psychoses.
J Nerv Ment Dis.
1982;
170
711-716
- 62 Müller A A, Stoll K D.
Carbamazepine and oxcarbazepine in the treatment of manic syndrome - Studies in Germany. In: Emrich H, Okuma T, Müller AA (eds) Anticonvulsants in affective disorders. Amsterdam;
Elsevier 1984: 139-147
- 63
Müller-Oerlinghausen B, Grof P, Schou M.
Lithium and suicide prevention.
Br J Psychiatry.
1999;
175
90-91
- 64
Müller-Oerlinghausen B, Retzow A, Henn F A, Giedke H, Walden J.
Valproate as an adjunct to neuroleptic medication for the treatment of acute episodes
of mania: a prospective, randomized, double-blind, placebo-controlled, multicenter
study. European Valproate Mania Study Group.
J Clin Psychopharmacol.
2000;
20
195-203
- 65
Neppe V M.
Carbamazepine as adjunctive treatment in nonepileptic chronic inpatients with EEG
temporal lobe abnormalities.
J Clin Psychiatry.
1983;
44
236-331
- 66
Nielsen O A, Johannessen A C, Bardrum B.
Oxcarbazepine-induced hyponatremia, a cross-sectional study.
Epilepsy Res.
1988;
2
269-271
- 67
Okuma T, Kishimoto A, Inoue K, Matsumoto H, Ogura A, Matsushita T, Naklao T, Ogura C.
Antimanic and prophylactic effects of carbamazepine (Tegretol) on manic depressive
psychosis: a preliminary report.
Folia Psychiatr Neurol Jpan.
1973;
27
617-630
- 68
Okuma T, Inanaga K, Otsuki S, Sarai K.
Comparison of the antimanic efficacy of carbamazepine and chlorpromazine: A double-blind
controlled study.
Psychopharmacology.
1979;
66
211-217
- 69
Pendlebury S C, Moses D K, Eadie M J.
Hyponatremia during oxcarbazepine therapy.
Hum Toxicol.
1989;
8
337-344
- 70
Pisani F, Fazio A, Oteri G, Artesi C, Xiao B, Perucca E, Di Perri R.
Effect of the antidepressant drug viloxazine on oxcarbazepine and its hydroxylated
metabolites in patients with epilepsy.
Acta Neurol Scand.
1994;
90
130-132
- 71
Post R M, Uhde T W, Putnam F W, Ballenger J C, Berrettini W H.
Kindling and carbamazepine in affective illness.
J Nerv Ment Dis.
1982;
170
717-731
- 72
Post R M, Denicoff K D, Frye M A, Dunn R T, Leverich G S, Osuch E, Speer A.
A history of the use of anticonvulsants as mood stabilizers in the last two decades
of the 20th Century.
Neuropsychobiology.
1998;
38
152-166
- 73
Puzy¿nski S, Klosiewicz L.
Valproic acid amide in the treatment of affective and schizoaffective disorders.
J Affect Disord.
1984;
6
116-121
- 74
Raptis C, Garacia-Borreguero D, Weber M M, Dose M, Bremer D, Emrich H M.
Anticonvulsants as adjuncts for the neuroleptic treatment of schizophrenic psychoses:
a clinical study with beclamide.
Acta Psychiatr Scand.
1990;
81
(2)
162-167
- 75
Reinikainen K J, Keränen T, Halonen T, Komulainen H, Riekkinnen P J.
Comparison of oxcarbazepine and carbamazepine: a double-blind study.
Epilepsy Res.
1987;
1
284-289
- 76
Ritola E, Malinen L.
A double blind comparison of carbamazepine and clomethiazole in the treatment of alcohol
withdrawal syndrome.
Acta Psychiatr Scand.
1981;
64
254-259
- 77
Schachter S C.
Oxcarbazepine: current status and clinical applications.
Experimental Opinions of Investigative Drugs.
1999;
8
1-10
- 78
Schachter S.
The next wave of anticonvulsants - Focus on levetiracetam, oxcarbazepine and zonisamide.
CNS Drugs.
2000;
14
(3)
229-249
- 79
Sindrup S H, Brosen K, Hansen M GJ, Aaes-Jorgensen T, Overb K F.
Pharmacokinetics of citalopram in relation to the sparteine and mephenytoin oxidation
polymorphism.
Ther Drug Monit.
1993;
15
11-17
- 80
Steinhoff B J, Stoll K-D, Stodieck S RG, et al.
Hyponatremic coma under oxcarbazepine therapy.
Epilepsy Res.
1992;
11
67-70
- 81
Takezaki I I, Hanaoka M.
The use of carbamazepine in the control of manic depressive states.
J Clin Psychiatry.
1971;
13
173-182
- 82
Tecoma E S.
Oxcarbazepine.
Epilepsia.
1999;
40
(5)
S37-S46
- 83
Theisohn M, Heimann G.
Dispositions of the antiepileptic oxcarbazepine and its metabolites in healthy volunteers.
Eur J Clin Pharmacol.
1982;
22
545-551
- 84
Thies-Flechtner K, Müller-Oerlinghausen B, Seibert W, Walther A, Greil W.
Effect of prophylactic treatment on suicide risk in patients with major affective
disorders. Data from a randomized prospective trial.
Pharmacopsychiatry.
1996;
29
103-107
- 85
Tiihonen J, Vartiainen H, Hakola P.
Carbamazepine-induced changes in plasma levels of neuroleptics.
Pharmacopsychiatry.
1995;
28
26-28
- 86
van Amelsvoort T, Bakshi R, Devaux C B, Schwabe S.
Hyponatremia associated with carbamazepine and oxcarbazepine therapy: a review.
Epilepsia.
1994;
35
(1)
181-188
- 87
van Heiningen P NM, Eve M D, Oosterhuis B, Jonkman J HG, de Bruin H, Hulsman J A,
Richens A, Jensen P K.
The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine.
Clin Pharmacol Ther.
1991;
50
410-419
- 88 Velikonja M, Heinrich K.
Effect of oxcarbazepine (GP 47.680) on affective and schizoaffective symptoms: A preliminary
report. In: Emrich H, Okuma T, Müller AA (eds) Anticonvulsants in affective disorders. Amsterdam;
Elsevier 1984: 208-210
- 89 Vencovsky¿ E, Soucek K, Kabes J.
Prophylactic effect of dipropylacetamide in patients with bipolar affective disorders. In: Emrich HM, Okuma T, Müller AA (eds) Anticonvulsants in affective disorders. Amsterdam;
Exerpta Medica 1984: 66-67
- 90
Wildgrube C.
Case studies on prophylactic long-term effects of oxcarbazepine in recurrent affective
disorders.
Inc Clin Psychopharmacol.
1990;
5
89-94
- 91
Zaccara G, Gangemi P F, Bendoni L, Menge G P, Monza G C.
Evaluation of the influence of single and repeated doses of oxcarbazepine on the pharmacokinetic
profile of felodipine.
Epilepsia.
1991;
32
(1)
71
Detlef E. DietrichM.D.
Department of Clinical Psychiatry and Psychotherapy
OE 7110
Medical School Hannover
30623 Hannover
Germany
Phone: + 49-511-5326749
Fax: + 49-511-5322415
Email: dietrich.detlef@mh-hannover.de
