Oxcarbazepine (Trileptal) is another so-called "new" seizure medication which has been successfully pushed on the field of psychiatry with absolutely no scientific research.  Claims were first published that it is effective at treating mania in 1983.  Although it is a very old medication, its marketing in the U.S. started around 2000.  No generic is available.  It is much more expensive, $248 vs. $22, than carbamazepine (Tegretol generic), which is very similar in effectiveness against seizures.

Although there is absolutely no research that oxcarbazepine helps treat or prevent mania, it very likely does, since carbamazepine is well proven to cause such a benefit.  Psychiatrists working closely with the manufacturer Novartis repeatedly claim that oxcarbazepine is well tolerated with considerably fewer side-effects that carbamazepine.  In fact, oxcarbazepine has only slightly fewer side-effects and these are primarily only during the first weeks of treatment.  More importantly, oxcarbazepine may in fact cause more deaths than carbamazepine, since it causes serious hyponatremia (SIADH) much more often than carbamazepine.

There appears never to have been a published scientific study of whether oxcarbazepine has any anti-manic benefits.  At least, there is no such mention on a PubMed search on 4/7/04.  Oxcarbazepine is very expensive, despite its being a very old medication.  Many psychiatrists have begun prescribing it, but I think that this is misguided.  Many proven alternatives are available.

The only real known advantage of oxcarbazepine is that it is much less likely to interact with other medications than is carbamazepine.  Carbamazepine lowers the blood levels of many anti-psychotics and divalproex by inducing the enzymes that metabolize these medications.  Since only a minority of bipolars will be on carbamazepine and these other medications at the same time, it seems much more responsible to reserve oxcarbazepine for situations such as this.  

I personally think that oxcarbazepine should not be used for bipolar disorder until at least one double-blind study shows that it helps.  We have just seen thousands of psychiatrists treat tens of thousands of bipolars with the worthless gabapentin and topiramate anti-seizure medications.  I hope oxcarbazepine doesn't prove worthless.  Giving a patient a totally untested medication is treating them as worse than guinea pigs.  At least guinea pigs are being used in a scientific study to measure some benefit.  When patients are given a totally untested medication, no possible scientific gain can results.

Wild Claims for Oxcarbazepine (Trileptal) from Italian University: Only 18 patients were studied in an open trial using oxcarbazepine as an add-on medication with no blinding of raters or control group. In the 12 month follow-up, seven patients did poorly and seven patients remained stable with four having mild to moderate mood difficulties. Authors make the wild claim that "our study suggests the potential usefulness of OXC as adjunctive therapy to lithium both in acute and long-term treatment of bipolar disorder. Oxcarbazepine as add-on treatment in patients with bipolar manic, mixed or depressive episode. Benedetti A, Lattanzi L, Pini S, Musetti L, Dell'Osso L, Cassano GB., University of Pisa. J Affect Disord. 2004 Apr;79(1-3):273-7. Ed: Trileptal is a old seizure medication recently resurrected and pushed for bipolar disorder without a single scientific study ever having being done so far as I can tell as of 4/7/04.  A Harvard psychiatrist and the above University of Pisa psychiatrist have been making claims that it is effective based only on small open trials.  There is no way to make any determination on effectiveness using an open trial.  

Extremely Irresponsible Claims from Harvard Psychiatrist: In a small, open study of only 42 patients and using only a very crude measure of improvement, Clinical Global Impressions-Improvement scale, a Harvard psychiatrist claims to have proven that oxcarbazepine is quite effective at treating mixed symptoms of bipolar disorders. Some patients received only oxcarbazepine and other received additional psychiatric medications. There was no comparison group, no randomization, no blinding of raters or patients. Ghaemi claims, " Oxcarbazepine was moderately to markedly effective in 24 subjects (57%)."  Sedation (17/42, 40%) was the most common side effect. Twenty-two patients (52%) stopped treatment, mostly due to side effects (12/22). Oxcarbazepine treatment of bipolar disorder. Ghaemi SN, Berv DA, Klugman J, Rosenquist KJ, Hsu DJ. J Clin Psychiatry. 2003 Aug;64(8):943-5. Ed: This study is nothing short of bizarre. Ghaemi deceives the reader into thinking that every patient who was reported to have improved while on oxcarbazepine, improved because of the medication.  Yet, every DB PC study ever done of bipolars has found a significant number of patients improve on placebos.  Of course, Ghaemi has worked closely with many pharmaceutical companies.  It is just possible that some conscious or unconscious bias might also be present.

Thyroid Suppressed by Oxcarbazepine and Carbamazepine: Of 19 girls 8-18 taking CBZ, 63% had either TSH or T-4 tests below the lower limits of normal and of 18 on OXC, 67% had below normal tests. In contrast, those on valproic acid (Depakene) did not. Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication. Vainionpaa LK, Mikkonen K, Rattya J, Knip M, Pakarinen AJ, Myllyla VV, Isojarvi JI. University of Oulu Epilepsia. 2004 Mar;45(3):197-203.

Side-Effects Very Common with Oxcarbazepine: According to the manufacturer, side-effects ( in percentages greater than placebo) of patients from 1200 mg/day of oxcarbazepine: double vision 25%, vomiting 20%, dizziness 19%, sleepiness 16%, nausea 15%, nystagmus 15%, staggering 12%, vertigo 10%, vision difficulty 10%, gait abnormality 9%, abdominal pain 8%, headache 5%, tremor 3%, dyspepsia 3%, muscle weakness 2%, coordination problem 2%, abnormal thinking 2%, acne 2%. Side-effects were still worse on high dosages. Many other side-effects occur in smaller numbers of patients. Of 500 children started on it, 11% had to stop due to side-effects. Of 300 adults, 9% had to stop. PDR 2004. Although similar data are not available for carbamazepine, claims that oxcarbazepine is better tolerated appears grossly exaggerated and without any scientific proof. In fact, there is evidence for at least some potentially serious side-effects that the exact opposite is true!

Birth Defects Highest with Oxcarbazepine: Prospective follow up of 970 pregnancies in women with epilepsy found that of their 979 offspring, 740 were exposed to maternal antiepileptic drugs (AED) during the first trimester of pregnancy. Major malformations were detected in 28 fetuses (3.8%) exposed to maternal AED and in 2 (0.8%) not exposed (p = 0.02). The occurrence of major malformations was independently associated with use of carbamazepine (adjusted OR 2.5), use of valproate (4.1), use of oxcarbazepine (10.8), low serum folate concentration (5.8), and low maternal level of education (3.0). Major malformations were not associated with seizures during the first trimester. Major malformations in offspring of women with epilepsy. Kaaja E, Kaaja R, Hiilesmaa V. Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Huch, Finland. Neurology. 2003 Feb 25;60(4):575-9

Hyponatremia Very Common with Oxcarbazepine: Severe hyponatremia is more frequent in adults treated with oxcarbazepine (OXC) than with carbamazepine (CBZ). 75 children with epilepsy before and during treatment with OXC and after replacing carbamazepine (CBZ) therapy with OXC therapy. All patients had normal sodium serum levels at the onset of OXC. During treatment with OXC we found hyponatremia (Na +< 135 mmol/l) without clinical symptoms in 26.6 % of the children, sodium levels below 125 mmol/l were observed in 2.6 %. Clinically relevant hyponatremia occurred in one girl only (1.3 %). In a subgroup of 27 children, in whom CBZ was directly replaced with OXC, hyponatremia without symptoms was found in one child under CBZ (3.7 %) and in six children under OXC (22.2 %). Dosage of OXC, serum levels of the active metabolite of OXC, antiepileptic comedication or patients' age and gender were of no predictive value for the development of hyponatremia. Oxcarbazepine-induced hyponatremia and the regulation of serum sodium after replacing carbamazepine with oxcarbazepine in children. Holtmann M, Krause M, Opp J, Tokarzewski M, Korn-Merker E, Boenigk HE. Mannheim, Germany. Neuropediatrics. 2002 Dec;33(6):298-300

Deaths Due to Oxcarbazepine: Two sudden deaths are reported by this author due to the Syndrome of Inappropriate Anti-Diuretic Hormone caused by oxcarbazepine. Seizure. 1998 Oct;7(5):419-20

Carbamazepine, Oxcarbazepine, and Valproate Affect Sperm Motility; Valproate Worst: 60 epileptic men were compared to 41 controls. The frequency of morphologically abnormal sperm was higher among CBZ-treated (p < 0.01), OXC-treated (p < 0.05), and VPA-treated men (p < 0.01) than among the control men. Moreover, both CBZ and VPA were associated with poor motility of sperm (p < 0.05). In addition, the frequency of abnormally low sperm concentration was high in men on CBZ (p < 0.001), and the frequency of any sperm abnormality was high in men on VPA (p < 0.01). The VPA-treated men with abnormal sperm had smaller testicular volumes than the control men (p = 0.003). CBZ, OXC, and VPA are associated with sperm abnormalities in men with epilepsy. In addition, VPA-treated men with generalized epilepsy who have abnormal sperm may have reduced testicular volume. Effect of epilepsy and antiepileptic drugs on male reproductive health. Isojarvi JI, Lofgren E, Juntunen KS, Pakarinen AJ, Paivansalo M, Rautakorpi I, Tuomivaara L. University of Oulu. Neurology. 2004 Jan 27;62(2):247-53

Oxcarbazepine Can Seriously Damage Kidneys: OXC has caused multiple cases of hyponatremic seizures and interstitial nephritis.

Carbamazepine Reduces Anti-psychotic Blood Levels Much More than Oxcarbazepine: Carbamazepine reduces clozapine blood levels by 47%. Pharmacopsychiatry. 1995 Jan;28(1):26-8. The same more be true for haloperidol and chlorpromazine. Psychopharmacology (Berl). 1994 Sep;116(1):115-6. Much less enzyme induction with oxcarbazepine. Br J Clin Pharmacol. 1991 Jan;31(1):65-71

Carbamazepine = Oxcarbazepine in Anti-Seizure Effectiveness: 235 seizure patients in a Danish DB 8-week study with 48 weeks of follow-up of carbamazepine vs. oxcarbazepine found no difference in effectiveness and only a trend toward better tolerability for oxcarbazepine. A double-blind study comparing oxcarbazepine and carbamazepine in patients with newly diagnosed, previously untreated epilepsy. Dam M, Ekberg R, Loyning Y, Waltimo O, Jakobsen K. Epilepsy Res. 1989 Jan-Feb;3(1):70-6; A small DB of 40 refractory seizure patients on phenytoin found no difference in efficacy between carbamazepine and oxcarbazepine but somewhat fewer side-effect with oxcarbazepine during the induction phase. Epilepsy Res. 1987 Sep;1(5):284-9

Oxcarbazepine a Very Old Medicine: Oxcarbazepine's first published claim of its effectiveness against mania were made in 1983! Neuropharmacology. 1983 Mar;22(3 Spec No):385-8.

Oxcarbazepine No Better at Seizure Suppression: Oxcarbazepine did as well as phenytoin and valproic acid in two different DB studies in suppressing seizures. It had significantly fewer side-effect drop-outs that phenytoin (2% vs. 10%) but more than valproate (15% vs. 10%). Epilepsy Res. 1997 Mar;26(3):451-60. Patients with allergic skin reactions on carbamazepine sometimes have similar reactions on oxcarbazepine, but not always. Epilepsia. 1987 Nov-Dec;28(6):693-8.