Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder.

[13] Common side effects include significant weight gain, feeling tired, dizziness, constipation, dry mouth, and restlessness.

[13] Other side effects include low blood pressure with standing, allergic reactions, neuroleptic malignant syndrome, diabetes mellitus, seizures, and tardive dyskinesia.

[27][31] Olanzapine is recommended by the National Institute for Health and Care Excellence as a first-line therapy for the treatment of acute mania in bipolar disorder.

[37] Olanzapine is associated with weight gain, which according to recent studies, may put olanzapine-treated patients' offspring at a heightened risk for neural tube defects (e.g. spina bifida).

[11] Citing an increased risk of stroke, in 2004, the Committee on the Safety of Medicines in the UK issued a warning that olanzapine and risperidone, both atypical antipsychotic medications, should not be given to elderly patients with dementia.

Owing to its partial dopaminergic agonist effect, aripiprazole is likely to reduce prolactin levels and, in some patients, can cause hypoprolactinaemia.

[45] It is not recommended to be used by IM injection in acute myocardial infarction, bradycardia, recent heart surgery, severe hypotension, sick sinus syndrome, and unstable angina.

Most antipsychotics, including olanzapine, may disrupt the body's natural thermoregulatory systems, thus permitting excursions to dangerous levels when situations (exposure to heat, strenuous exercise) occur.

[medical citation needed] The US Food and Drug Administration (FDA) requires atypical antipsychotics to include a warning about the risk of developing hyperglycemia and diabetes, both of which are factors in the metabolic syndrome.

[49][50] Studies have indicated that olanzapine carries a greater risk of causing and exacerbating diabetes than another commonly prescribed atypical antipsychotic, risperidone.

[61] One small, open-label, nonrandomized study suggests that taking olanzapine by orally dissolving tablets may induce less weight gain,[62] but this has not been substantiated in a blinded experimental setting.

[63] The incidence of PDSS with olanzapine pamoate is estimated to be 0.07% of administrations, and is unique among other second-generation, long-acting antipsychotics (e.g. paliperidone palmitate), which do not appear to carry the same risk.

[63] PDSS may occur due to accidental injection and absorption of olanzapine pamoate into the bloodstream, where it can act more rapidly, as opposed to slowly distributing out from muscle tissue.

[63] This is why the FDA advises that people who are injected with olanzapine pamoate be watched for 3 hours after administration, in the event that PDSS occurs.

Death has been reported after an acute overdose of 450 mg, but also survival after an acute overdose of 2000 mg.[69] Fatalities generally have occurred with olanzapine plasma concentrations greater than 1000 ng/mL post mortem, with concentrations up to 5200 ng/mL recorded (though this might represent confounding by dead tissue, which may release olanzapine into the blood upon death).

[70] No specific antidote for olanzapine overdose is known, and even physicians are recommended to call a certified poison control center for information on the treatment of such a case.

[70] Olanzapine has been used as a hallucinogen antidote to block the effects of serotonergic psychedelics like psilocybin and lysergic acid diethylamide (LSD).

[96] P-glycoprotein transports a myriad of drugs across a number of different biological membranes (found in numerous body systems) including the blood–brain barrier (a semipermeable membrane that filters the contents of blood prior to it reaching the brain); P-GP inhibition could mean that less brain exposure to olanzapine results from this interaction with the P-glycoprotein.

[100][101] Additionally, it also exhibits a relatively low affinity for serotonin 5-HT1, GABAA, β-adrenergic receptors, and benzodiazepine binding sites.

[70] Routine, pharmacokinetic monitoring of olanzapine plasma levels is generally unwarranted, though unusual circumstances (e.g. the presence of drug-drug interactions) or a desire to determine if patients are taking their medicine may prompt its use.

In the final two steps, 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile was reduced with stannous chloride in ethanol to give the substituted thienobenzodiazepine ring system, and this was treated with methylpiperazine in a mixture of dimethyl sulfoxide and toluene as solvent to produce the drug.

[116] Eli Lilly has faced many lawsuits from people who claimed they developed diabetes or other diseases after taking Zyprexa, as well as by various governmental entities, insurance companies, and others.

[119][120] The documents were provided to the Times by Jim Gottstein, a lawyer who represented mentally ill patients, who obtained them from a doctor, David Egilman, who was serving as an expert consultant on the case.

[117] The Times of London also received the documents and reported that as early as 1998, Lilly considered the risk of drug-induced obesity to be a "top threat" to Zyprexa sales.

[120] On 9 October 2000, senior Lilly research physician Robert Baker noted that an academic advisory board to which he belonged was "quite impressed by the magnitude of weight gain on olanzapine and implications for glucose.

[123] In September 2008, Judge Weinstein issued an order to make public Lilly's internal documents about the drug in a different suit brought by insurance companies, pension funds, and other payors.

[123] In 2009, Eli Lilly pleaded guilty to a US federal criminal misdemeanor charge of illegally marketing Zyprexa for off-label use and agreed to pay $1.4 billion.

[127] In 2021, Gottstein summarized this tangle of legal activities, and their impact on the political landscape of psychiatry and antipsychiatry in the US, in The Zyprexa Papers.

[135] The daytime sedation experienced with olanzapine is generally comparable to quetiapine and lurasidone, which is a frequent complaint in clinical trials.