Educationals

Lithium, Carbamazepine and Valproate

In the management of manic or hypomanic episode, lithium, carbamazepine or valproate can be used. As the therapeutic effect of these medicines is delayed by 8-10 days, most of the patients require either additional benzodiazepine or combination of lithium with carbamazepine or valproate, or an additional antipsychotic for the rapid control of symptoms.

It may be preferable to start lithium carbonate in the dose of 300 mg three times a day after two days in order to avoid nausea, vomiting or diarrhoea associated with high dose of lithium. Most of the adult patients (weight around 454-60 kg) require about 900 to 1200 mg of lithium per day in divided does (i.e. about 20 mg/kg body weight). One may prefer to use a sustained release or controlled release preparation of lithium in order to reduce the gastrointestinal side effects and reduce the frequency of administration to once or twice a day.

In patients who do not tolerate lithium or in whom lithium is contraindicated due to some renal or cardiac problem, carbamazepine or valproate may be used. Similarly in a patient getting frequent episodes (4 or more per year rapid cycling) or those who have dysphoric mania, valproate may be preferable to lithium.

Carbamazepine may be started in the dose of 200 mg at bed time and gradually increased by 200 mg on alternate days to 600-1200 mg/day in divided doses. Controlled release and retard preparations are available, and may be preferable.

Sodium valproate may be started with 200-500 mg at bed time and increased to 1200-1500 mg/day. In severe cases a loading dose of 1000-1500 mg/day may be used on the very first day. Like lithium and carbamazepine, valproate is also available in a controlled release form. Valproate should be used with caution in patients with liver disease. When combined with antipsychotics it can result in increase sedation and severe extrapyramidal reaction. In some cases one may have to use a combination of lithium and carbamazepine or lithium and valproate.

After the remission of manic episode, the treatment may be discontinued after 6-8 months if the patient does not require maintenance therapy.

Antipsychotics and Benzodiazepines

As mentioned earlier, for rapid symptomatic control, along with these drugs one may have to add antipsychotics like haloperidol or chlorpromazine and/or benzodiazepines like clonazepam or lorazepam.

Some clinicians also use clozapine, due to its heavy sedative action, for control of manic episode. Clozapine should not be used along with carbamzepine as they both are known to cause agranulocytosis.

The addition of neuroleptics is not very much preferred by some clinicians as it carries an extra risk for adverse effects like extrapyramidal reactions, tardive dyskinesia and neuroleptic malignant syndrome.

Electroconvulsive Therapy

ECT may be used as a quick and effective treatment for the moderate to severe manic episode. While the patient is receiving ECT, it may be preferable to either discontinue or reduce the dose of these mood stabilizers. Valproate and carbamazepine increase the seizure threshold and thus the patient may not get seizure when administered ECT, while patients receiving lithium when treated concomitantly with ECT may develop confusion.

Newer Drugs

In recent years other anticonvulsants like lamotrigine and gabapentin, calcium channel blockers like nifedepine, amlodipine and nimodipine and other drugs like clonidine have been tried in the treatment of this disorder.