UNDER REVIEW (September 2016)
Mechanism of Action:
Olanzapine is a thienobenzodiazepine, one of the ‘atypical’ antipsychotic drugs. Olanzapine has a high affinity for dopamine and serotonin (5-HT) receptors. Like most atypical antipsychotics compared to the older typical ones, it has a lower affinity for histamine, cholinergic muscarinic and alpha adrenergic receptors. The mechanism of action of olanzapine is unknown but the antipsychotic activity is probably mediated primarily by antagonism at dopamine D2 receptors. Serotonin antagonism may also play a role in the effectiveness of olanzapine, but the significance of 5-HT2A antagonism is debated. Antagonism at muscarinic cholinoceptors, histamine receptors and alpha adrenoceptors may explain some of the side effects of olanzapine, such as anticholinergic effects, weight gain, sedation and orthostatic hypotension.
Lecture and CAL materials:
Drug specifics
| Alternative drug name | not specified |
| Effects | Main indications for chronic use are schizophrenia, combination therapy for mania, and preventing recurrence in bipolar disorder. It is also used acutely by IM injection for control of agitation and disturbed behaviour in schizophrenia or mania. |
| Adverse actions | Adverse events include dry mouth, dizziness, sedation, insomnia, orthostasis, akathisia, and weight gain. Olanzapine is reported to cause extrapyramidal symptoms, tardive dyskinesia and neurological malignant syndrome, although at a much reduced rate when compared to the classical antipsychotics. Olanzapine, probably to a greater extent than other atypical drugs is associated with impaired glucose tolerance, diabetes and the 'metabolic syndrome'. In 2004, the UK Committee for the Safety of Medicines (CSM)issued a warning that olanzapine and another atypical antipsychotic, risperidone should not be given to elderly patients with dementia, because of an increased risk of stroke. Atypical antipsychotics may affect performance of skilled tasks (e.g. driving); effects of alcohol are enhanced. Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse. |
| Dose | Given by mouth or IM injection. |
| Interactions | See BNF. |
| Contraindications | not specified |
| Comments | The ‘atypical antipsychotics' include olanzapine, amisulpride, aripiprazole, clozapine, quetiapine, risperidone, and zotepine. They may be better tolerated than other antipsychotics; extrapyramidal symptoms may be less frequent. Most cause little or no elevation of prolactin concentration; when changing from other antipsychotics, a reduction in prolactin may increase fertility. Clozapine is licensed for the treatment of schizophrenia only in patients unresponsive to other drugs because it can cause agranulocytosis and its use is restricted to patients registered with a clozapine patient monitoring service. NICE GUIDANCE (June 2002) recommended that: (a) the atypical antipsychotics should be considered when choosing first-line treatment of newly diagnosed schizophrenia; (b) an atypical antipsychotic is considered the treatment option of choice for managing an acute schizophrenic episode when discussion with the individual is not possible; (c) an atypical antipsychotic should be considered for an individual who is suffering unacceptable side-effects from a conventional antipsychotic; (d) an atypical antipsychotic should be considered for an individual in relapse whose symptoms were previously inadequately controlled; (e) changing to an atypical antipsychotic is not necessary if a conventional antipsychotic controls symptoms adequately and the individual does not suffer unacceptable side-effects; (f) clozapine should be introduced if schizophrenia is inadequately controlled despite the sequential use of two or more antipsychotics (one of which should be an atypical antipsychotic) each for at least 6–8 weeks. Flupentixol is a type of thioxanthine drug and acts by antagonism of D1 and D2 dopamine receptors (as well as serotonin). The typical antipsychotics are less commonly used now that the atypical antipsychotics are available (with fewer side effects). |
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