Antipsychotic drugs are used in schizophrenia to control acute symptoms, to prevent relapses and, less effectively, to ameliorate chronic schizophrenic symptoms. They are also used to combat the symptoms of mania and to help in the management of organic syndromes such as brain damage and dementia.
The antipsychotic action of these drugs may be attributable to anti-dopaminergic activity in the limbic system. Blockade of this transmitter in other brain areas is responsible for adverse extrapyramidal reactions and hyperprolactinaemia. Antipsychotics interact to varying degrees with a wide range of other neuroreceptors in the CNS, which may lead to the different adverse effects-see below.
Phenothiazines can be divided into three main groups:
Group I Aliphatic compounds—chlorpromazine, levomepromazine and promazine—have pronounced sedative effects and moderate extrapyramidal and autonomic effects.
Group II Piperidines-periciazine—have moderate sedative effects, fewer extrapyramidal but more autonomic effects.
Group III Piperazines—prochlorperazine and trifluoperazine—have fewer sedative effects, pronounced extrapyramidal but less autonomic effects.
Other groups include the butyrophenones (benperidol and haloperidol), diphenylbutylpiperidines (pimozide) and thioxanthenes (flupentixol and zuclopenthixol) with actions similar to the Group III piperazines, while the substituted benzamides (sulpiride) may be less sedative and associated with a lower incidence of tardive dyskinesia.
The newer atypical antipsychotics may be better tolerated than other antipsychotics. Clozapine has a low potential for producing extrapyramidal effects. Clozapine is effective in relieving both positive and negative schizophrenic symptoms in patients refractory to classical antipsychotics. Patients should be carefully monitored due to the risk of agranulocytosis and the product should be prescribed and dispensed by brand name to limit disruption of haematological monitoring. Amisulpride, cariprazine, lurasidone, olanzapine, paliperidone, quetiapine and risperidone also produce fewer extrapyramidal side effects than classical antipsychotics and are effective against the positive and negative symptoms of schizophrenia. The partial dopamine agonist aripiprazole has both agonist and antagonist activity depending on the surrounding levels of dopamine. It acts as an antagonist to reduce the positive symptoms of schizophrenia and as an agonist to reduce the negative symptoms of the disease. It does not produce extrapyramidal reactions nor does it increase prolactin levels. Asenapine is licensed for the treatment of manic episodes in bipolar disorder.
Lithium salts are used to treat mania and hypomania and to prevent episodes of mania and depression. The carbonate salt is more widely used but the citrate is also available. Lithium salts have a narrow therapeutic/toxic ratio and treatment requires facilities for monitoring serum levels. Bioavailability varies from product to product, particularly sustained-release preparations, therefore, lithium preparations should be prescribed by brand name and patients should not be transferred from one preparation to another without full clinical assessment and retitration.
Carbamazepine, normally used as an anticonvulsant, is also effective in manic depressive psychosis that is unresponsive to lithium, and in patients who experience multiple mood swings each year.
Similarly, the anticonvulsants valproic acid and sodium valproate can be used to treat manic episodes in bipolar disorder when lithium is contraindicated or not tolerated.