Olanzapine (Zyprexa): an atypical antipsychotic used for schizophrenia and bipolar disorder

How it works and formulations

Olanzapine acts on multiple neurotransmitter receptors, notably antagonizing dopamine (D2) and serotonin (5-HT2A) receptors, along with effects at histamine, adrenergic and muscarinic sites. It is available as oral tablets and orally disintegrating tablets, and as intramuscular formulations including a short-acting injection and a long-acting pamoate depot for extended maintenance therapy.

Common clinical uses

• Treatment of schizophrenia, including acute psychosis and relapse prevention.
• Management of acute manic or mixed episodes and long-term maintenance in bipolar disorder.
• Adjunctive use with antidepressants or other agents in certain mood or anxiety presentations.
• Occasionally used off-label for severe agitation or insomnia in psychiatric settings.

Side effects and monitoring

Olanzapine is associated with clinically important adverse effects. Weight gain and metabolic disturbances (increased blood glucose, dyslipidemia and risk of diabetes) are common and may require regular monitoring of weight, fasting glucose and lipids. Sedation, anticholinergic effects, orthostatic hypotension and elevated prolactin can occur. Extrapyramidal symptoms are generally less frequent than with older antipsychotics but remain possible. Use in elderly patients with dementia-related psychosis is linked to increased mortality and is generally avoided.

Dosage, interactions and precautions

Dosing is individualized; typical oral regimens are started at a low dose and adjusted for response and tolerability. Olanzapine interacts with central nervous system depressants and with agents that alter its metabolism (for example, some anticonvulsants and certain antidepressants), so clinicians review concomitant medications. Pregnancy and breastfeeding require careful risk–benefit assessment. Regular metabolic and cardiovascular monitoring is recommended during treatment.

History and notable facts

Developed and originally marketed by Eli Lilly, olanzapine became widely used after regulatory approval in the 1990s and later became available in generic forms. Its effectiveness for a range of psychotic and mood disorders made it a mainstay of psychiatric pharmacotherapy, while concerns about metabolic effects have driven guidance on monitoring and informed selection among antipsychotic options.