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Carbamazepine, oxcarbazepine, and eslicarbazepine 

Carbamazepine, oxcarbazepine, and eslicarbazepine
Chapter:
Carbamazepine, oxcarbazepine, and eslicarbazepine
Author(s):

Andrea E. Cavanna

DOI:
10.1093/med/9780198791577.003.0003
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Carbamazepine is a first-generation antiepileptic drug (AED; Fig. 3.1) known with the proprietary brand name of Tegretol® (Novartis, Basel) in the UK and USA (Fig. 3.2). Oxcarbazepine is a second-generation AED (Fig. 3.1) supplied under the proprietary brand name of Trileptal® (Novartis, Basel) in the UK and USA (Fig. 3.3). Eslicarbazepine is a third-generation AED (Fig. 3.1) sold under the proprietary brand names of Zebinix® (Eisai, Hatfield) in the UK and Aptiom® (Sunovion, Marlborough, MS) in the USA (Fig. 3.4).

Fig. 3.1 Chronology of the clinical use of carbamazepine and its derivatives oxcarbazepine and eslicarbazepine

Fig. 3.1 Chronology of the clinical use of carbamazepine and its derivatives oxcarbazepine and eslicarbazepine

Fig. 3.2 Chemical structure of carbamazepine

Fig. 3.2 Chemical structure of carbamazepine

Fig. 3.3 Chemical structure of oxcarbazepine

Fig. 3.3 Chemical structure of oxcarbazepine

Fig. 3.4 Chemical structure of eslicarbazepine

Fig. 3.4 Chemical structure of eslicarbazepine

Preparations

Carbamazepine

Tablets

  • Carbamazepine 100 mg (84-tab pack).

  • Carbamazepine 200 mg (84-tab pack).

  • Carbamazepine 400 mg (56-tab pack).

Modified-release tablets

  • Carbamazepine 200 mg (56-tab pack £5.20).

  • Carbamazepine 400 mg (56-tab pack £10.24).

Oral suspension

  • Carbamazepine 20 mg/mL (300 mL £6.12).

Suppository

  • Carbamazepine 125 mg (5-suppository pack £8.03).

  • Carbamazepine 250 mg (5- suppository pack £10.71).

Oxcarbazepine

Tablets

  • Oxcarbazepine 150 mg (50-tab pack).

  • Oxcarbazepine 300 mg (50-tab pack).

  • Oxcarbazepine 600 mg (50-tab pack).

Oral suspension

  • Oxcarbazepine 60 mg/mL (250 mL £40.80).

Eslicarbazepine

Tablets

  • Eslicarbazepine 800 mg (30-tab pack £136.00).

Generic formulation

Carbamazepine

The Medicines and Healthcare Products Regulatory Agency/Commission on Human Medicines (MHRA/CHM) advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):

  • Category 1: doctors are advised to ensure that their patients are maintained on a specific manufacturer’s product.

Oxcarbazepine and eslicarbazepine

MHRA/CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):

  • Category 2: the need for continued supply of a particular manufacturer’s product should be based on clinical judgment and consultation with the patient and/or carer, taking into account factors such as seizure frequency and treatment history.

Indications

Carbamazepine

Epilepsy: monotherapy and adjunctive therapy of focal and generalized seizures.

Recommendations

  • Seizure types: first line (generalized tonic-clonic seizures, focal seizures), adjunctive (focal seizures), contraindicated (generalized tonic-clonic seizures if there are absence or myoclonic seizures, or if juvenile myoclonic epilepsy is suspected, tonic/atonic seizures, absence seizures, myoclonic seizures).

  • Epilepsy types: first line (epilepsy with generalized tonic-clonic seizures only, benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome, late-onset childhood occipital epilepsy), adjunctive (benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome, late-onset childhood occipital epilepsy), contraindicated (absence syndromes, juvenile myoclonic epilepsy, idiopathic generalized epilepsy, Dravet syndrome, Lennox–Gastaut syndrome).

    • Psychiatry: prophylaxis of manic-depressive phases in patients with bipolar disorder unresponsive to lithium therapy; treatment of alcohol withdrawal symptoms (unlicensed).

    • Neurology: treatment of paroxysmal pain in trigeminal neuralgia and diabetic neuropathy (unlicensed).

Oxcarbazepine

Epilepsy: monotherapy and adjunctive therapy of focal and generalized seizures.

Recommendations summarized from NICE (2012)

  • Seizure types: first line (generalized tonic-clonic seizures, focal seizures), adjunctive (focal seizures), contraindicated (generalized tonic-clonic seizures if there are absence or myoclonic seizures, or if juvenile myoclonic epilepsy is suspected, tonic/atonic seizures, absence seizures, myoclonic seizures).

  • Epilepsy types: first line (epilepsy with generalized tonic-clonic seizures only, benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome, late-onset childhood occipital epilepsy), adjunctive (benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome, late-onset childhood occipital epilepsy), contraindicated (absence syndromes, juvenile myoclonic epilepsy, idiopathic generalized epilepsy, Dravet syndrome, Lennox–Gastaut syndrome).

Eslicarbazepine

Epilepsy: monotherapy and adjunctive therapy of focal seizures.

Recommendations summarized from NICE (2012)

  • Seizure types: adjunctive (focal seizures).

Dose titration

Carbamazepine

  • Epilepsy—immediate release: 100–200 mg od/bd, increased by 100–200 mg every 14 days; usual maintenance 800–1200 mg daily, in divided doses (max. 2000 mg daily).

  • Epilepsy—prolonged release: 50–200 mg bd, increased by 100–200 mg every 14 days; usual maintenance 800–1200 mg daily, divided into two doses (max. 2000 mg daily).

  • Bipolar disorder—immediate release: 400 mg daily, in divided doses, increased by 100–200 mg every 14 days; usual maintenance 400–600 mg daily, in divided doses (max. 1600 mg daily).

  • Bipolar disorder—prolonged release: 200 mg bd, increased by 100–200 mg every 14 days; usual maintenance 200–300 mg bd (max. 1600 mg daily).

If stopping carbamazepine, patients with bipolar disorder need to reduce the dose gradually over a period of at least 4 weeks.

Oxcarbazepine

300 mg bd, increased by 300–600 mg every 7 days; usual maintenance 600–2400 mg daily, in divided doses.

Eslicarbazepine

400 mg od, increased to 800 mg od after 1–2 weeks (max. 1200 mg od).

Plasma levels monitoring

Carbamazepine

Correlations between dosages and plasma levels of carbamazepine, as well as between plasma levels, and clinical efficacy or tolerability, are rather tenuous. However, monitoring of the plasma levels (therapeutic range in the treatment of epilepsy 4–12 mg/L) may be useful in selected conditions, such as a dramatic increase in seizure frequency/verification of patient compliance, during pregnancy, in suspected absorption disorders, in suspected toxicity due to polymedication.

Oxcarbazepine

Plasma level monitoring of oxcarbazepine is not routinely warranted. Although correlations between dosage and plasma levels of oxcarbazepine, and between plasma levels and clinical efficacy or tolerability are rather tenuous, monitoring of the plasma levels may be useful to rule out non-compliance or in patients with changes in renal function, patients with concomitant use of liver enzyme-inducing drugs and during pregnancy.

Eslicarbazepine

Plasma level monitoring has a minimal role in the therapeutic use of eslicarbazepine due to the relatively predictable pharmacokinetics of the drug.

Cautions

Carbamazepine

  • Patients with a history of hepatic porphyrias.

  • Patients with a history of bone marrow depression.

  • Patients with atrioventricular block.

  • Patients with a history of haematological reactions to other drugs.

  • Patients with susceptibility to angle-closure glaucoma.

  • Patients with skin reactions.

  • Patients with cardiac disease.

  • Patients with absence and myoclonic seizures.

Oxcarbazepine

  • Patients with acute porphyrias.

  • Patients with cardiac disease.

  • Patients with hyponatraemia.

Eslicarbazepine

  • Elderly patients.

  • Patients with hyponatraemia.

  • Patients with prolonged PR interval.

Adverse effects

Carbamazepine

Carbamazepine can be associated with adverse effects at the level of the nervous system and other systems (Table 3.1).

Table 3.1 Estimated frequency of adverse effects of carbamazepine

Very common (>1 in 10 patients on carbamazepine)

Nervous system

  • ataxia

  • dizziness

  • tiredness

Other systems

  • nausea and vomiting

  • leucopenia

  • skin rash

Common (>1 in 100 patients on carbamazepine)

Nervous system

  • headache

  • diplopia

Other systems

  • dry mouth

  • hyponatraemia

  • oedema

  • thrombocytopenia

  • weight gain

Uncommon (>1 in 1000 patients on carbamazepine)

Nervous system

  • involuntary movements

  • nystagmus

Other systems

  • constipation

  • diarrhoea

Rare (>1 in 10,000 patients on carbamazepine)

Nervous system

  • agitation

  • aggression

  • confusion

  • dysarthria

  • depression

  • hallucinations

  • paraesthesias

  • restlessness

  • weakness

Other systems

  • abdominal pain

  • anorexia

  • arrhythmias

  • delayed multi-organ hypersensitivity disorder

  • hypertension

  • hypotension

  • jaundice

  • lupus erythematosus-like syndrome

  • lymphadenopathy

Very rare (<1 in 10,000 patients on carbamazepine)

Nervous system

  • hearing disorders

  • psychosis

  • taste disturbance

Other systems

  • acne

  • alopecia

  • alterations in skin pigmentation

  • anaemia

  • angle-closure glaucoma

  • aseptic meningitis

  • conjunctivitis

  • dyspnoea

  • gynaecomastia and galactorrhoea

  • hirsutism

  • impotence, loss of libidio and impaired male fertility

  • kidney failure

  • liver failure

  • muscle pain and spasms

  • ostomalacia and osteoporosis

  • photosensitivity

  • purpura

  • severe skin reaction (Stevens-Johnson syndrome)*

  • stomatitis

  • sweating

  • thromboembolism and thrombophlebitis

  • toxic epidermal necrolysis

  • urinary frequency or retention

* Before deciding to initiate treatment, patients of Han Chinese and Thai origin should, whenever possible, be screened for HLA-B*1502, as this allele strongly predicts the risk of severe carbamazepine-associated Stevens–Johnson syndrome.

Some adverse effects (mainly affecting the nervous system) are dose-dependent and may be dose-limiting. The incidence of these adverse effects (higher at the start of treatment and in the elderly) can be reduced by offering a modified-release preparation or altering the timing of medication. Although the manufacturer recommends blood counts, and hepatic and renal functions tests, evidence of practical value is uncertain.

Oxcarbazepine

Oxcarbazepine can be associated with adverse effects at the level of the nervous system and other systems (Table 3.2).

Table 3.2 Estimated frequency of adverse effects of oxcarbazepine

Very common (>1 in 10 patients on oxcarbazepine)

Nervous system

  • diplopia

  • dizziness

  • headache

  • tiredness

Other systems

  • nausea and vomiting

Common (>1 in 100 patients on oxcarbazepine)

Nervous system

  • agitation

  • amnesia

  • anxiety

  • ataxia

  • confusion

  • depression

  • drowsiness

  • nystagmus

  • tremor

  • weakness

Other systems

  • abdominal pain

  • acne

  • alopecia

  • constipation

  • diarrhoea

  • hyponatraemia

  • skin rash

Uncommon (>1 in 1,000 patients on oxcarbazepine)

Nervous system

Other systems

  • leucopenia

  • urticaria

Rare (>1 in 10,000 patients on oxcarbazepine)

Nervous system

Other systems

Very rare (<1 in 10,000 patients on oxcarbazepine)

Nervous system

Other systems

  • arrhythmias

  • atrioventricular block

  • delayed multi-organ hypersensitivity disorder

  • hepatitis

  • lupus erythematosus-like syndrome

  • pancreatitis

  • severe skin reaction (Stevens-Johnson syndrome)*

  • thrombocytopenia

  • toxic epidermal necrolysis

* Before deciding to initiate treatment, patients of Han Chinese and Thai origin should, whenever possible, be screened for HLA-B*1502, as this allele strongly predicts the risk of severe oxcarbazepine-associated Stevens–Johnson syndrome.

Eslicarbazepine

Eslicarbazepine can be associated with adverse effects at the level of the nervous system and other systems (Table 3.3).

Table 3.3 Estimated frequency of adverse effects of eslicarbazepine

Very common (>1 in 10 patients on eslicarbazepine)

Nervous system

  • dizziness

  • tiredness

Other systems

Common (>1 in 100 patients on eslicarbazepine)

Nervous system

  • ataxia

  • diplopia

  • headache

  • insomnia

  • tremor

  • weakness

Other systems

  • decreased appetite

  • diarrhoea

  • hyponatraemia

  • nausea and vomiting

  • skin rash

Uncommon (>1 in 1000 patients on eslicarbazepine)

Nervous system

  • agitation

  • amnesia

  • anxiety

  • confusion

  • depression

  • disaesthesia

  • dysarthria

  • hyperactivity

  • movement disorders

  • nystagmus

  • parosmia

  • tinnitus

Other systems

  • abdominal pain

  • alopecia

  • anaemia

  • bradycardia

  • chest pain

  • constipation

  • dehydration

  • dry mouth

  • electrolyte imbalances

  • epistaxis

  • gingival hyperplasia

  • hypertension

  • hyponatraemia

  • hypotension

  • hypothyroidism

  • liver problems

  • malaise

  • myalgia

  • peripheral oedema

  • stomatitis

  • urinary tract infection

  • weight loss

Rare (>1 in 10,000 patients on eslicarbazepine)

Nervous system

Other systems

Very rare (<1 in 10,000 patients on eslicarbazepine)

Nervous system

Other systems

  • leucopenia

  • pancreatitis

  • thrombocytopenia

Rare adverse reactions, such as bone marrow depression, anaphylactic reactions, severe cutaneous reactions (e.g. Stevens–Johnson syndrome), systemic lupus erythematosus, or serious cardiac arrhythmias did not occur during the placebo-controlled studies of the epilepsy programme with eslicarbazepine acetate. However, they have been reported with carbamazepine and oxcarbazepine. Therefore, their occurrence after treatment with eslicarbazepine acetate cannot be excluded.

Interactions

Carbamazepine

With AEDs

  • Plasma concentration of carbamazapine is increased by vigabatrin, whereas plasma concentration of the active metabolite carbamazepine 10,11-epoxide is increased by primidone and valproate (reduce carbamazepine dose to avoid increased risk of toxicity).

  • Plasma concentration of carbamazapine is reduced by cytochrome P450 3A4 inducers (including eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and, possibly, clonazepam).

  • Carbamazapine is a cytochrome P450 3A4 inducer and can decrease the plasma concentration of clobazam, clonazepam, ethosuximide, lamotrigine, oxcarbazepine, primidone, tiagabine, topiramate, valproate, and zonisamide.

  • Co-administration of levetiracetam has been reported to increase carbamazepine-induced toxicity; cross-sensitivity has been reported with oxcarbazepine and phenytoin.

With other drugs

  • Plasma concentration of carbamazapine is reduced by cytochrome P450 3A4 inducers aminophylline, cisplatin, doxorubicin, St John’s wort (Hypericum perforatum), isotretinoin, rifampicin, and theophylline (consider increasing the dose of carbamazapine).

  • Plasma concentration of carbamazapine is increased by cytochrome P450 3A4 inhibitors: acetazolamide, azoles (antifungals), cimetidine, ciprofloxacine, danazol, dextropropoxyphene, diltiazem, fluoxetine, fluvoxamine, isoniazid, loratadine, macrolide antibiotics, olanzapine, omeprazole, paroxetine, protease inhibitors (antivirals), trazodone, and verapamil. Plasma concentration of the active metabolite carbamazepine-10,11-epoxide is increased by progabide, quetiapine, valnoctamide, and valpromide.

  • Carbamazepine is a cytochrome P450 3A4 inducer and can decrease the plasma concentration of albendazole, alprazolam, aprepitant, aripiprazole, atorvastatin, bromperidol, buprenorphine, bupropion, calcium channel blockers (e.g. felodipine), cerivastatin, ciclosporin, citalopram, clozapine, corticosteroids (e.g. prednisolone, dexamethasone), cyclophosphamide, digoxin, doxycycline, everolimus, haloperidol, hormonal contraceptives (oestrogens and progesterones), imatinib, itraconazole, ivabradine, lapatinib, levothyroxine, lovastatin, methadone, mianserin, olanzapine, oral anticoagulants (e.g. warfarin), paliperidone, paracetamol (acetaminophen), protease inhibitors (antivirals), quetiapine, rifabutin, risperidone, sertraline, simvastatin, tacrolimus, tadalafil, temsirolimus, theophylline, tramadol, trazodone, tricyclic antidepressants, voriconazole, and sirolimus.

With alcohol/food

  • Drinking alcohol may affect patients more than usual; eating grapefruit, or drinking grapefruit juice, may increase chance of experiencing adverse effects.

Oxcarbazepine

With AEDs

  • Strong inducers of cytochrome P450 enzymes (i.e. carbamazepine, phenytoin, phenobarbital) have been shown to decrease the plasma levels of oxcarbazepine’s pharmacologically active metabolite.

  • Oxcarbazepine and its pharmacologically active metabolite are weak inducers of the cytochrome P450 enzymes CYP3A4 and CYP3A5 responsible for the metabolism of a other AEDs (e.g. carbamazepine) resulting in a lower plasma concentration of these medicinal products.

  • Concomitant therapy of oxcarbazepine and lamotrigine has been associated with an increased risk of adverse events (nausea, somnolence, dizziness, and headache).

With other drugs

  • Oxcarbazepine and its pharmacologically active metabolite are weak inducers of the cytochrome P450 enzymes CYP3A4 and CYP3A5 responsible for the metabolism of a large number of drugs, for example, immunosuppressants (e.g. ciclosporin, tacrolimus) and oral contraceptives (see carbamazepine’s interactions).

With alcohol/food

  • Caution should be exercised if alcohol is taken in combination with oxcarbazepine, due to a possible additive sedative effect.

  • There are no specific foods that must be excluded from diet when taking oxcarbazepine.

Eslicarbazepine

With AEDs

  • Concomitant administration of eslicarbazepine and carbamazepine or phenytoin can result in a decrease in exposure to the active metabolite of eslicarbazepine, most likely caused by an induction of glucuronidation. therefore, the dose of eslicarbazepine may need to be increased if used concomitantly with carbamazepine.

  • Concomitant administration of eslicarbazepine and phenytoin can result in an increase in exposure to phenytoin, most likely caused by an inhibition of CYP2C19.

  • Concomitant use of eslicarbazepine with oxcarbazepine is not recommended because this may cause overexposure to the active metabolites.

With other drugs

  • Concomitant administration of eslicarbazepine and combined oral contraceptive, simvastatin, rosuvastatin, and warfarin results in a decrease in systemic exposure to levonorgestrel and ethinylestradiol, simvastatin, rosuvastatin, and warfarin, most probably caused by an induction of CYP3A4.

  • Based on a structural relationship of eslicarbazepine to tricyclic antidepressants, an interaction between eslicarbazepine and monoamino oxidase inhibitors is theoretically possible.

With alcohol/food

  • There are no known specific interactions between alcohol and eslicarbazepine, and there are no specific foods that must be excluded from the diet when taking eslicarbazepine.

Special populations

Carbamazepine

Hepatic impairment

  • Metabolism impaired in advanced liver disease.

Renal impairment

  • Use with caution.

Pregnancy

  • Developmental disorders and malformations (including spina bifida), as well as other congenital anomalies (including craniofacial defects, such as cleft lip/palate, cardiovascular malformations, hypospadias, and anomalies involving various body systems) have been reported in association with the use of carbamazepine during pregnancy. In women of childbearing age carbamazepine should, wherever possible, be prescribed as monotherapy, because the incidence of congenital abnormalities in the offspring of women treated with a combination of antiepileptic drugs is greater (especially if valproate is part of the polytherapy).

  • Pregnant women with epilepsy should be treated with minimum effective doses of carbamazepine and monitoring of plasma levels is recommended (aiming at the lower side of the therapeutic range, as there is evidence to suggest that the risk of malformation with carbamazepine may be dose-dependent).

  • Should a woman on carbamazepine decide to breastfeed, the infant should be monitored for possible adverse effects, as carbamazepine can be excreted in considerable amounts in breastmilk, which in combination with slow infantile elimination can result in plasma concentrations at which pharmacological effects occur. Since there have been reports of cholestatic hepatitis in neonates exposed to carbamazepine during antenatal and or during breastfeeding, breastfed infants of mothers treated with carbamazepine should be carefully observed for adverse hepatobiliary effects.

Oxcarbazepine

Hepatic impairment

  • Mild to moderate hepatic impairment does not affect the pharmacokinetics of oxcarbazepine and its active metabolite. Oxcarbazepine has not been studied in patients with severe hepatic impairment.

Renal impairment

  • Dose adjustment (halve initial dose and increase according to response at intervals of at least 1 week) is recommended in patients with renal impairment and lower creatinine clearance.

Pregnancy

  • Data on oxcarbazepine associated with congenital malformation are limited. There is no increase in the total rate of malformations with oxcarbazepine, compared with the rate observed in the general population. However, a moderate teratogenic risk cannot be completely excluded.

  • If women receiving oxcarbazepine become pregnant or plan to become pregnant, the use of this drug should be carefully re-evaluated. Minimum effective doses should be given, and monotherapy whenever possible should be preferred at least during the first 3 months of pregnancy.

  • During pregnancy, an effective antiepileptic oxcarbazepine treatment must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus.

  • Oxcarbazepine and its active metabolite are excreted in human breastmilk. As the effects on the infant exposed to oxcarbazepine by this route are unknown, oxcarbazepine should not be used during breast-feeding.

Eslicarbazepine

Hepatic impairment

  • No dose adjustment is recommended in patients with mild to moderate hepatic impairment.

  • The pharmacokinetics of eslicarbazepine has not been evaluated in patients with severe hepatic impairment.

Renal impairment

  • Dose adjustment (reduce initial dose to 400 mg every other day for 2 weeks, then 400 mg od) is recommended in patients with renal impairment and lower creatinine clearance.

Pregnancy

  • There are no data from the use of eslicarbazepine in pregnant women. If women receiving eslicarbazepine become pregnant or plan to become pregnant, the use of eslicarbazepine should be carefully re-evaluated. Minimum effective doses should be given and monotherapy, whenever possible, should be preferred, at least during the first 3 months of pregnancy.

  • It is unknown whether eslicarbazepine acetate is excreted in human milk. As a risk to the breastfed child cannot be excluded, breastfeeding should be discontinued during treatment with eslicarbazepine

Behavioural and cognitive effects in patients with epilepsy

Carbamazepine

Carbamazepine is characterized by a good behavioural and cognitive profile in patients with epilepsy. Overall, adverse psychiatric effects (especially irritation, agitation, depression) are rarely reported in this patient population. Moderate cognitive problems affecting attention, memory, and language have occasionally been reported (especially at high doses).

Oxcarbazepine

Similarly to carbamazepine, oxcarbazepine is generally considered to pose a low risk for adverse psychiatric effects (especially emotional lability, insomnia, abnormal thinking—usually occurring at high dosages) in patients with epilepsy. Moderate cognitive problems affecting attention and concentration have occasionally been reported (especially at high doses).

Eslicarbazepine

For this third-generation agent, clinical experience is still limited, and little is known about its positive and negative psychotropic properties, and their implications for the management of behavioural symptoms in patients with epilepsy.

Psychiatric use

Carbamazepine

Carbamazepine was approved as a treatment for acute mania in 2004, decades after it was recognized as an effective alternative to lithium in the management of bipolar illness. Data from open-label trials suggest that carbamazepine is effective in the prophylaxis of bipolar disorder or acute mania, but may be less effective than valproate or lithium. However, carbamazepine has been suggested to be a better alternative for atypical manifestations of bipolar disorder, such as rapid cycling course, mood-incongruent delusions, or in the presence of other co-morbid psychiatric or neurological conditions. Carbamazepine may also be effective in unipolar depression, whereas its utility in schizophrenia is uncertain. In rarer cases, carbamazepine has been used to treat aggressive behaviour and to facilitate sedatives/alcohol withdrawal, but there is no solid evidence to date to establish its efficacy in this domain. To summarize, evidence is strongest to support the mood stabilizing properties of carbamazepine (Fig. 3.5).

Fig. 3.5 Level of evidence supporting the psychiatric use of carbamazepine in patients with behavioural symptoms

Fig. 3.5 Level of evidence supporting the psychiatric use of carbamazepine in patients with behavioural symptoms

Oxcarbazepine

Oxcarbazepine’s principal use in patients with psychiatric disorder is the treatment of bipolar disorder (mania), although there are no approved indications in psychiatry. Oxcarbazepine has been proposed as a potential option for add-on therapy in the treatment of bipolar disorder, although it remains to be determined whether oxcarbazepine is effective in the acute treatment of bipolar depression or the maintenance treatment of bipolar disorder. Preliminary evidence suggests that oxcarbazepine may exert beneficial effects on behavioural disorders, particularly impulsive aggression. There is also evidence for the potential usefulness of oxcarbazepine in obsessive-compulsive disorder and anxiety disorders (panic disorder, post-traumatic stress disorder). Other potential off-label uses are alcohol withdrawal and dependence, benzodiazepine withdrawal, and cocaine abuse/dependence (Fig. 3.6).

Fig. 3.6 Level of evidence supporting the psychiatric use of oxcarbazepine in patients with behavioural symptoms

Fig. 3.6 Level of evidence supporting the psychiatric use of oxcarbazepine in patients with behavioural symptoms

Eslicarbazepine

For this third-generation agent, clinical experience is still limited and little is known about its positive and negative psychotropic properties, and their implications for the management of behavioural symptoms in patients with epilepsy.

Overall rating

Carbamazepine

Carbamazepine is characterized by a good range of antiepileptic indications, with acceptable risk of interactions in polytherapy. It has a very good behavioural tolerability profile and widespread psychiatric use (Table 3.4).

Table 3.4 Overall rating of carbamazepine

Antiepileptic indications

☺☺

Interactions in polytherapy

Behavioural tolerability

☺☺☺

Psychiatric use

☺☺☺

Key: ☺☺☺ = very good; ☺☺ = good; ☺ = acceptable.

Oxcarbazepine

Oxcarbazepine is characterized by a good range of antiepileptic indications, with acceptable risk of interactions in polytherapy. It has a very good behavioural tolerability profile and potential for widespread psychiatric use (Table 3.5).

Table 3.5 Overall rating of oxcarbazepine

Antiepileptic indications

☺☺

Interactions in polytherapy

Behavioural tolerability

☺☺☺

Psychiatric use

☺☺

Key: ☺☺☺ = very good; ☺☺ = good; ☺ = acceptable.