Carbamazepine is a dibenzazepine derivative with antiepileptic and psychotropic properties. It is used to control secondarily generalised tonic-clonic seizures and partial seizures, and in some primary generalised seizures. Carbamazepine is also used in the treatment of trigeminal neuralgia and has been tried with variable success in glossopharyngeal neuralgia and other severe pain syndromes associated with neurological disorders such as tabes dorsalis and multiple sclerosis. Another use of carbamazepine is in the management of bipolar disorder unresponsive to lithium.
In the treatment of epilepsy, the dose of carbamazepine should be adjusted to the needs of the individual patient to achieve adequate control of seizures; this usually requires total plasma-carbamazepine concentrations of about 4 to 12 micrograms/mL (17 to 50 micromoles/litre). A low initial dose of carbamazepine is recommended to minimise adverse effects. The suggested initial oral dose is 100 to 200 mg once or twice daily gradually increased by increments of up to 200 mg daily every week to a usual maintenance dose of 0.8 to 1.2 g daily in divided doses; up to 2 g daily may occasionally be necessary. For details of doses in children, see below.
Oral carbamazepine is usually given in divided doses 2 to 4 times daily. A twice-daily regimen may be associated with improved compliance but can produce widely fluctuating plasma-carbamazepine concentrations that lead to intermittent adverse effects. Twice-daily dosage may nonetheless be suitable for patients receiving carbamazepine monotherapy; modified-release formulations can minimise fluctuations in plasma concentration and may also allow effective twice-daily use. Different preparations vary in bioavailability and it may be prudent to avoid changing the formulation. The time and manner of taking carbamazepine should be standardised for the patient since variations might affect absorption with consequent fluctuations in the plasma concentrations.
Carbamazepine may be given by the rectal route in doses up to a maximum of 250 mg every 6 hours to patients for whom oral treatment is temporarily not possible. The dosage should be increased by about 25% when changing from an oral formulation to suppositories, and it is recommended that the rectal route should not be used for longer than 7 days.
As with other antiepileptics, withdrawal of carbamazepine therapy or transition to or from another type of antiepileptic therapy should be made gradually to avoid precipitating an increase in the frequency of seizures. For a discussion on whether or not to withdraw antiepileptic therapy in seizure-free patients.
The treatment of trigeminal neuralgia is typically begun with low oral doses, such as 100 mg of carbamazepine twice daily (although up to 200 mg twice daily has been suggested in the UK), and increased gradually as needed to maintain freedom from pain. This is usually at maintenance doses of 400 to 800 mg in divided doses; up to 1.2 g daily is considered standard maintenance in the United States of America (US and USA), while UK licensed product information considers that up to 1.6 g daily may be needed in some patients. When pain relief has been obtained attempts should be made to reduce, and if possible stop, therapy, until another attack occurs.
For the management of bipolar disorder, carbamazepine is given in an initial oral dose of 400 mg daily in divided doses, increased gradually as necessary up to a maximum of 1.6 g daily; the usual maintenance dose range is 400 to 600 mg daily.
Administration. A modified-release formulation of carbamazepine can reduce fluctuations in carbamazepine concentrations, and tolerability and seizure control in patients with epilepsy may be improved. Such formulations should be considered in patients receiving high doses who suffer intermittent adverse effects, and might also permit a reduction to twice-or even, in some patients, once-daily dosage. However, bioavailability appears to be slightly less than conventional preparations and dosage adjustments may be required when changing between formulations.
Administration in children. In the UK, the usual recommended oral dose of carbamazepine for generalised tonic-clonic and partial seizures in children is 10 to 20 mg/kg daily in divided doses. Alternatively the daily dose may be given according to age as follows:
- up to 1 year: 100 to 200 mg
- 1 to 5 years: 200 to 400 mg
- 5 to 10 years: 400 to 600 mg
- 10 to 15 years: 0.6 to 1 g
As with adults, children should be started on a low initial dose of carbamazepine to minimise adverse effects; the BNFC suggests that those aged 1 month to 12 years may initially be given 5 mg/kg at night or 2.5 mg/kg twice daily, increasing by 2.5 to 5 mg/kg every 3 to 7 days as necessary to a usual maintenance dose of 5 mg/kg 2 or 3 times daily. Older children may be given the usual adult dose (see above) although a maximum of 1.8 g daily has been suggested.
The BNFC also states that these doses may be used for the treatment of neuropathic pain and some movement disorders, and for mood stabilisation.
Carbamazepine may be given rectally to children in whom oral treatment is temporarily not possible; the BNFC suggests this route may be used from 1 month of age. Doses should be about 25% greater than the corresponding oral dose, to a maximum of 250 mg, and given up to 4 times daily.
Bipolar disorder. Carbamazepine may be given as an alternative to lithium or valproate in patients with bipolar disorder. Studies of its efficacy have been conflicting; although clearly effective in some patients, at least one early study suggested that short-term benefit was not sustained in the longer term. More recent results have suggested that lithium or valproate are generally more effective, but that carbamazepine may conceivably have a role in patients with nonclassical features. Carbamazepine has also been used with lithium, particularly in patients unresponsive to either drug alone; although there are suggestions that the combination may be more effective than monotherapy, particularly in patients with a history of rapid cycling, it is associated with a potential risk of serious neurotoxicity — see Antidepressants, under Interactions, above. While some commentators have suggested that carbamazepine is falling out of favour with specialists prescribing for bipolar disorder, a more recent literature review concluded that it was still a feasible treatment option.
Depression. Carbamazepine has been tried for the augmentation of antidepressant therapy in the treatment of resistant depression. However, such combined therapy may lead to interactions — see also Antidepressants under Interactions, above.
Diabetes insipidus. Cranial diabetes insipidus is usually treated by replacement therapy with antidiuretic hormone (ADH) in the form of desmopressin. Carbamazepine is one of a variety of other drugs that have been tried to promote ADH secretion, although some consider that it is usually ineffective and has unwanted effects. Doses of 200 to 400 mg daily by mouth have been given. See also Effects on Electrolytes under Adverse Effects, above.
Epilepsy. Carbamazepine is one of the drugs of choice for partial seizures with or without secondary generalisation. It has been used for generalised tonic-clonic seizures (although valproate is the drug of choice where these occur in primary generalised epilepsy), but it may exacerbate absence and myoclonic seizures.
Hemifacial spasm. Carbamazepine has been reported to have been of help in the treatment of hemifacial spasm.
Hiccup. For the management of intractable hiccups see under Chlorpromazine. Carbamazepine may be of value for the treatment of neurogenic hiccups such as those that occur in multiple sclerosis. Carbamazepine has also been reported to have been of benefit in 3 patients with diaphragmatic flutter, a rare disorder associated with involuntary contractions of the diaphragm.
Hyperactivity. When drugs are indicated for attention deficit hyperactivity disorder initial treatment is usually with a central stimulant but meta-analysis of a small number of trials has provided evidence that carbamazepine may be effective.
Lesch-Nyhan syndrome. The severe self-mutilation that occurs in patients with Lesch-Nyhan syndrome has been reported to improve in those given antiepileptics such as carbamazepine.
Movement disorders. Carbamazepine is one of many drugs that have been tried in the symptomatic treatment of chorea; there have been anecdotal reports of benefit in both non-hereditary and hereditary choreas. Carbamazepine is also among the drugs that have been tried in the treatment of dystonias that have not responded to levodopa or antimuscarinics. Although some patients may benefit from carbamazepine, it is not generally recommended because of a relatively low success rate and the possibility of adverse effects. Carbamazepine therapy has also been associated with movement disorders — see Effects on the Nervous System: Extrapyramidal Effects under Adverse Effects, above.
Carbamazepine has also been used in resistant cases of tardive dyskinesia (see under Extrapyramidal Disorders). Although not licensed in the UK for movement disorders in children, the BNFC suggests that carbamazepine may be tried in disorders such as paroxysmal kinesigenic choreoathetosis in doses similar to those used for the treatment of epilepsy (see Administration in Children, above).
Neonatal seizures. Carbamazepine has been tried in the management of neonatal seizures.
Neuropathic pain. As well as being used to ease the pain of trigeminal neuralgia (see below) carbamazepine may be of use in other neuropathic pain including that associated with diabetic neuropathy. A systematic review concluded that about two-fifths of patients who take carbamazepine for neuropathic pain will achieve moderate pain relief, but this was based on small studies. The authors found no evidence that carbamazepine was effective for acute pain.
Carbamazepine has also been tried in an attempt to prevent the painful sensory neuropathy associated with oxaliplatin treatment; results of preliminary studies have been conflicting. Although not licensed in the UK for neuropathic pain in children, the BNFC suggests that carbamazepine may be tried in doses similar to those used for the treatment of epilepsy (see Administration in Children, above).
Nocturnal enuresis. Carbamazepine has been reported to be of benefit in the treatment of primary nocturnal enuresis; a dose of 200 mg at night for 15 nights markedly decreased the frequency of bed-wetting episodes in 8 children.
For the conventional management of nocturnal enuresis see site.
Psychiatric disorders. Carbamazepine has psychotropic properties and has been tried in the management of several psychiatric disorders, particularly in patients with bipolar disorder (see above). Carbamazepine has also been used with mixed results in various disorders for the control of symptoms such as agitation, aggression, and rage (see Disturbed Behaviour). It may produce modest benefit when used as an adjunct to antipsychotics in the management of refractory schizophrenia but any improvement appears to be related to its mood stabilising effect. However, a more recent systematic review, albeit based on small studies, found carbamazepine to have no significant benefit either as monotherapy or as an adjunct to antipsychotics; the authors considered that further randomised studies may be warranted. Carbamazepine also has the potential to reduce serum concentrations of antipsychotics, resulting in clinical deterioration (see under Interactions for Chlorpromazine). Carbamazepine has also been tried in post-traumatic stress disorder.
Restless legs syndrome. The aetiology of restless legs syndrome (see Sleep-associated Movement Disorders) is obscure and treatment has been largely empirical. In a double-blind study involving 174 patients carbamazepine appeared to be more effective than placebo. Oxcarbazepine has been reported to be of benefit in restless legs syndrome induced by paroxetine.
Tinnitus. Treatment of tinnitus is difficult, and many drugs have been tried. Although carbamazepine has been reported to be effective in some patients, it is rarely used because of its adverse effects.
Trigeminal neuralgia. Carbamazepine is the drug of choice in the treatment of the acute stages of trigeminal neuralgia. Satisfactory pain relief may be achieved in 70% or more of patients, although increasingly larger doses may be required and adverse effects can be troublesome.
Withdrawal syndromes. Carbamazepine has been tried in the prophylaxis and treatment of various withdrawal syndromes. Reduction in cocaine use associated with carbamazepine treatment was found in one short-term controlled study, although a systematic review of data from later studies concluded that there was no evidence to support the use of carbamazepine in the treatment of cocaine dependence. It has been reported to be of benefit in some patients during benzodiazepine withdrawal but such adjunct therapy is not usually indicated. Carbamazepine has been shown to be effective in the treatment of symptoms of the alcohol withdrawal syndrome but as there are limited data on its efficacy in preventing associated delirium tremens and seizures it is usually recommended that it should only be used as an adjunct to benzodiazepine therapy. Carbamazepine has also been studied as an aid in the treatment of alcohol dependence.
International Brand Drug Names
The information about drugs (tablets, pills, capsules, creams, solution, nasal spray, inhaler) around the world.
British Pharmacopoeia, 2008 edition: Carbamazepine Tablets;
The United States Pharmacopeia 31, 2008: Carbamazepine Extended-Release Tablets; Carbamazepine Oral Suspension; Carbamazepine Tablets.
Argentina: Actinerval; Carbagramon; Carbamat; CMP; Conformal; Elebe; Tegretol;
Australia: Tegretol; Teril;
Austria: Deleptin; Neurotop; Sirtal; Tegretol;
Brazil: Carmazin; Convulsan; Tegretard; Tegretol; Tegrex; Tegrezin; Uni Carbamaz;
Canada: Novo-Carbamaz; Tegretol;
Chile: Carbactol Retard; Eposal; Tegretal;
Czech Republic: Biston; Neurotop; Tegretol; Timonil;
Denmark: Nordotol; Tegretol; Trimonil;
Finland: Neurotol; Tegretol;
Germany: Carba; Carbabeta; Carbadura; Carbaflux; Carbagamma; Carbium; Espa-lepsin; Finlepsin; Fokalepsin; Sirtal; Tegretal; Timonil;
Hong Kong: Carzepin; CP-Carba; Tegretol; Teril;
Hungary: Azepal; Finlepsin; Neurotop; Stazepine; Tegretol; Timonil;
India: Carbacontin; Cizetol; Mazetol; Tegrital;
Indonesia: Bamgetol; Tegretol; Teril;
Ireland: Gericarb; Tegretol; Temporol;
Israel: Carbi; Tegretol; Teril; Timonil;
Malaysia: Taver; Tegretol;
Mexico: Adepril; Apobace; Bioneuril; Bioreunil; Carbalan; Carbasal; Carbaval; Carbazep; Carbazina; Carpin; Clostedal; Dateril; Neugeron; Neurolep; Sepibest; Tegretol; Trepina; Ultrepyl; Volutol; Zepiken;
Netherlands or Holland: Tegretol;
Norway: Tegretol; Trimonil;
New Zealand: Tegretol; Teril;
Philippines: Carbilepp; Epazin; Epikor; Tegretol;
Poland: Amizepin; Finlepsin; Neurotop; Tegretol; Timonil;
Russia: Carbalepsin (Карбалепсин); Carbapin (Карбапин); Finlepsin (Финлепсин); Tegretol (Тегретол); Zeptol (Зептол);
South Africa: Degranol; Tegretol;
Singapore: Carbatol; Neurotop; Tegretol;
Sweden: Hermolepsin; Tegretol; Trimonil;
Switzerland: Carsol; Neurotop; Tegretol; Timonil;
Thailand: Antafit; Carbatol; Carbazene; Carmapine; Carpine; Carzepine; Mapezine; Panitol; Taver; Tegretol; Zeptol;
Turkey: Karazepin; Karbalex; Karbasif; Karberol; Kazepin; Tegretol;
UK or Britain: Arbil; Carbagen; Epimaz; Tegretol; Teril; Timonil;
US or USA: Atretol; Carbatrol; Epitol; Equetro; Tegretol; Teril;
Venezuela: Convulex; Gabox; Tanfedin; Tegretol.
Selections from the book: “Martindale: The Complete Drug Reference. Thirty-sixth edition”. Pharmaceutical Press. 2009