There are no published double-blind, placebo-controlled studies on the use of carbamazepine in children and adolescents for the treatment of bipolar disorders. carbamazepine increases limbic gamma amino butyric acid (GABA) type B receptors, decrease GABA and dopamine turnover, inhibits inositol transport, and weakly inhibits calcium influx by a NMDA mediated effects in preclinical trials. Chronic Lithium, carbamazepine, valproate use increases hippocampal GABA-B and decreases gamma amino butyric acid turnover, suggesting that hippocampal GABA-B receptor mechanisms and a decrease of GABA turnover could be effects involved in medications that stabilize mood. A list of some of the complex carbamazepine functions appears in an endnote.
The active carbamazepine-E metabolite can yield therapeutic and adverse effects similar to carbamazepine but is not detected in conventional carbamazepine assays. Thus, the unwary clinician may misinterpret the significance of therapeutic or adverse effects associated with low or moderate carbamazepine serum concentrations. The CSF and serum levels of carbamazepine-E (or carbamazepine-E / carbamazepine), but not of carbamazepine, are associated with improvement of mood disorders and clinical improvement of depression, respectively.
Carbamazepine in blood is 76% protein bound, and is more rapidly metabolized to carbamazepine-10,11-epoxide (a metabolite with equipotency to carbamazepine as an anticonvulsant in animal screens) in younger age groups than adults. If there is no hint of therapeutic response at moderate doses, it is unlikely that pushing the medication to very high doses will be beneficial. Carbamazepine alters the concentration and metabolism of many medications.
Carbamazepine is available as chewable 100 mg tablets, tablets of 200 mg, XR tablets of 100,200,400 mg, and as a suspension of 100mg/5ml. Carbamazepine suspension should notbe administered concomitantly with other medication suspensions because of the risk of precipitation.
Carbamazepine should not be used in patients with history of bone marrow depression, porphyria, hypersensitivity to the medication, or sensitivity to TCAs, or concomitantly with MAO inhibitors. Carbamazepine is indicated in the following neurological (seizure disorders and trigeminal neuralgia, migraines, and others) and psychiatric conditions.
Treatment of Acute Mania
Carbamazepine and valproate are more effective than lithium in producing remissions in patients with bipolar disorders with comorbid substance abuse. Carbamazepine antimanic response is considered to be comparable to lithium or neuroleptics, or in other studies, to valproate. The overall aggregated antimanic efficacy reported in mixed studies (16 with carbamazepine, 4 with oxcarbazepine) in 179 patients was 59%; the one for lithium was 61%; for adjunctive neuroleptic, 56%; and adjunctive placebo, 33%. These results should be read with caution; the number of patients is small and the aggregation of carbamazepine and oxcarbazepine is not justified. Actually, it is misleading, because it gives oxcarbazepine a legitimacy that needs to demonstrated; oxcarbazepine needs to prove its efficacy and tolerability on its own and should not do so by riding on the coattails of the parent compound.
Carbamazepine may have an equal prophylactic antimanic and antidepressant efficacy in contrast to its less potent acute antidepressant efficacy compared to the antimanic effects. Carbamazepine efficacy in rapid cycling patients is mixed.
In maintenance treatment, carbamazepine seems to be more effective than lithium in patients with nonclassical manias (bipolar II, bipolar NOS, bipolar disorder with mood incongruent delusions or comorbidity). Carbamazepine may be effective in valproate resistant illness, and a carbamazepine plus valproate combination may be effective in patients with little or no response to either agent alone. It is proposed that the left insula hypermetabolism is a marker for carbamazepine response.
The overall rate of prophylaxis efficacy in mixed studies in 242 patients was reported as 54%. There were 13 studies with carbamazepine and 2 studies with oxcarbazepine (one study has 8 and the other 4 patients). The response rates for lithium were 63%, and for placebo 22%. The reservations expressed about the antimanic efficacy are also applicable for the ones on prophylaxis. Regarding long-term treatment safety, there are only data related to six-month treatment in epileptic children.