Efficacy of Carbamazepine and Its Derivatives in the Treatment of Bipolar Disorder

Abstract

Background and Objectives: This review is dedicated to the use of carbamazepine and its derivatives oxcarbazepine and eslicarbazepine in bipolar disorder and their relative strengths in treating and preventing new depressive or manic episodes. This paper will discuss the evidence of their efficacy relative to the polarity of relapse from controlled acute and maintenance/relapse prevention studies in bipolar patients. Materials and Methods: A Medline search was conducted for controlled acute and maintenance studies with carbamazepine, oxcarbazepine, and eslicarbazepine in bipolar disorder. In addition, abstracts reporting on controlled studies with these medications from key conferences were taken into consideration. Results: Information was extracted from 84 articles on the acute and prophylactic efficacy of the medications under consideration. They all appear to have stronger efficacy in treating acute mania than depression, which also translates to better protection against manic than depressive relapses for carbamazepine. Still, there is a paucity of controlled acute studies on bipolar depression for all and, with the exception of carbamazepine, a lack of long-term monotherapy maintenance data. For eslicarbazepine, the efficacy in bipolar disorder remains largely unknown. Especially with carbamazepine, tolerability issues and drug–drug interactions need to be kept in mind. Conclusions: Two of the medications discussed in this review, carbamazepine and oxcarbazepine, match Class A criteria according to the criteria proposed by Ketter and Calabrese, meaning acute antimanic efficacy, prevention of manic relapses, and not causing or worsening depression.

Characterization in Inhibitory Effectiveness of Carbamazepine in Voltage-Gated Na+ and Erg-Mediated K+ Currents in a Mouse Neural Crest-Derived (Neuro-2a) Cell Line

“…Taken together, the activity of Na V channels in excitable cells (e.g., Neuro-2a cells) may conceivably confer the susceptibility to modifications by CBZ. The differential inhibition by CBZ of I Na(T) and I Na(L) is of particular significance and may participate in its regulation of the electrical behaviors of excitable cells occurring in vivo [ 4 , 7 , 8 , 9 , 10 , 31 , 35 ].…”

“…Carbamazepine (CBZ, Tegretol ® , 5H-dibenzo[b,f]azepine-5-carboxamide) is an aromatic anticonvulsant that has been widely used for the treatment of seizure disorders and neuropathic pain specifically for trigeminal neuralgia [ 1 , 2 , 3 , 4 , 5 ]. This drug has been also demonstrated as an adjunctive treatment in schizophrenia or myotonia and as a second-line agent in bipolar disorder [ 6 , 7 , 8 , 9 , 10 ].…”

Mycotherapy: Potential of Fungal Bioactives for the Treatment of Mental Health Disorders and Morbidities of Chronic Pain

“…Mood disorders * Lithium Multiple mechanisms including modulation of (GABA)-ergic and glutamatergic neurotransmission, and alteration of voltage-gated ion channels or intracellular signalling pathways [22,23] First-line treatment for prevention of manic and depressive episodes of bipolar disorder (BD) [24] Cardiac problems, cognitive problems, acne, psoriasis, thyroid problems, nausea, vomiting, weight gain, hyponatremia, sedation, decreased libido, and teratogenic [25] valproic acid First-line treatment for acute mania and maintenance of BD [26] Cardiac problems, cognitive problems, hair loss, hypothyroidism, aplastic anaemia, Leukopenia, increased transaminases, hepatitis, SLE-like syndrome, hyponatremia, tremor, decreased libido, infertility and teratogenic [25] Carbamazepine Effective as a monotherapy to treat manic symptoms of bipolar or as adjunct to lithium or valproic acid [27] Cardiac problems, cognitive problems, acne, hair loss, hypothyroidism, PCOS. diarrhoea, nausea, vomiting, pancreatitis, increased transaminases, metabolic syndrome, weight gain, sedation, tremor, decreased sexual function, infertility and teratogenic [25] Psychotic disorders First-generation antipsychotics (FGA) e.g., Chlorpromazine, haloperidol D2 antagonists: work by inhibiting dopaminergic neurotransmission [28] Effective in the treatment and maintenance of schizophrenia, acute mania with psychotic symptoms, major depressive order with psychotic features, and delusional disorder [28] Adverse (5-HT 2A/2C antagonism) receptors [31] Effective as an adjunctive therapy in treatment of AN, increasing appetite and decreasing anxiety and ruminating thoughts involving body image and food [32] Dizziness, orthostatic hypotension, hypercholesterolemia, hypertriglyceridemia, hyperglycaemia, weight gain, extra-pyramidal symptoms, dry mouth, hyperprolactinemia, and insomnia [32] Antidepressants(SSRIs, SNRIs, TCAs, MAOIs) Defined above…”

The Purinergic System as a Target for the Development of Treatments for Bipolar Disorder

“…Their role in BD can be hypothesized from the therapeutic effect of carbamazepine, the first anti-seizure drug used for BD back in the 1970s. Carbamazepine is currently considered a second-line mood stabilizer with limited applicability for treating acute mania and mixed episodes or for maintenance and preventive therapy [128][129][130][131]. Its mechanism of action includes the antagonism of A 1 R, which results in long-term mRNA upregulation and an increased number of A 1 R receptors.…”