Second-generation (atypical) antipsychotic
Antagonist at dopamine D2 and serotonin 5-HT2A receptors; also blocks histamine H1, muscarinic M1–5, and alpha-1 adrenergic receptors, contributing to its sedative, anticholinergic, and metabolic side effects
Schizophrenia, bipolar I disorder (manic/mixed episodes, maintenance), adjunctive treatment of major depressive disorder (MDD) in combination with fluoxetine
Severe agitation, psychosis, or aggression in dementia, anorexia nervosa, chemotherapy-induced nausea and vomiting, impulse control disorders, postpartum psychosis, post-stroke affective lability, post-stroke aggression
Oral tablets, orally disintegrating tablets (ODT), intramuscular (IM) short-acting injection, and extended-release IM depot
5–10 mg p.o. nightly; titrate in 2.5–5 mg increments as tolerated
5–20 mg/day
Half-life ~30 hours; metabolized via CYP1A2 and glucuronidation; steady state in ~1 week
Weight gain, sedation, increased appetite, dry mouth, dizziness, orthostatic hypotension, constipation, metabolic disturbances (hyperglycemia, hyperlipidemia)
Diabetic ketoacidosis, neuroleptic malignant syndrome (NMS), tardive dyskinesia, seizures, anticholinergic delirium
Monitor weight, BMI, fasting glucose, lipids, blood pressure, and EPS every 3–6 months
Increased risk of mortality in elderly patients with dementia-related psychosis
Olanzapine carries a high risk of metabolic complications, including substantial weight gain, insulin resistance, and dyslipidemia. It should be used with caution or avoided in individuals with preexisting diabetes mellitus, obesity, or cardiovascular disease. It may have utility in treatment-resistant mood or psychotic disorders, but careful monitoring is required. Co-administration with parenteral benzodiazepines should be avoided due to the risk of profound sedation and respiratory depression. Dose reductions or slower titration may be appropriate in older adults or those with hepatic impairment.