Olanzapine

Olanzapine is an atypical antipsychotic medication indicated for the treatment of schizophrenia and for acute manic or mixed episodes in bipolar I disorder. It is also used as part of fixed-dose combinations, such as olanzapine with fluoxetine, for bipolar depression and treatment-resistant depression in some settings. The drug may be prescribed for long-term maintenance to reduce relapse in schizophrenia or bipolar disorder, with clinical decisions guided by individual response and tolerability.

The mechanism of action of olanzapine involves antagonism of dopamine D2 receptors and serotonin 5-HT2A receptors, which is believed to contribute to its antipsychotic effects. It also exhibits activity at other receptors, including histamine H1 and adrenergic receptors, which can contribute to sedation and weight gain. Compared with many first-generation antipsychotics, olanzapine tends to have a relatively lower risk of extrapyramidal symptoms but a higher tendency to cause metabolic side effects.

Olanzapine is available in oral tablets and orally disintegrating tablets, and an intramuscular form is used for agitation in acute schizophrenia. A long-acting injectable form (olanzapine pamoate) is approved for maintenance therapy in some regions, often under a restricted program due to risk of post-injection delirium/sedation syndrome. Warnings include an increased risk of metabolic side effects such as weight gain, hyperglycemia, and dyslipidemia, as well as sedation and orthostatic effects. Elderly patients with dementia-related psychosis have an increased mortality risk and should not use olanzapine for this indication.

Pharmacokinetically, olanzapine is well absorbed orally and primarily metabolized in the liver by enzymes including CYP1A2, with contributions from 2D6 and 3A4. Smoking can accelerate metabolism via CYP1A2, reducing drug levels. Common drug interactions involve CNS depressants and agents affecting hepatic enzymes. Consideration of metabolic health, weight, and glucose tolerance is important during long-term treatment.