Olanzapine
A second-generation antipsychotic, usually taken as a daily tablet. It works well for many people, but often causes weight gain and raises blood sugar and blood fats.
At a glance
- Type
- Medicine: second-generation (atypical) antipsychotic
- Used for
- Schizophrenia, including to prevent relapse, and mania in bipolar disorder
- Status
- Approved in Europe
- First used
- 1996, approved across the European Union
- Evidence
- EstablishedHow evidence is rated
- Administration
- Tablets, once a day, with or without food. Also as a short-acting injection for severe agitation, and as a long-acting injection
- Starts to work
- Improvement can take several days to some weeks
- Common side effects
- Weight gain, sleepiness, raised blood sugar and blood fats, dizziness on standing up
- Checks needed
- Weight at the start, after 4, 8 and 12 weeks, then every 3 months. Blood sugar at the start, after 12 weeks, then yearly. Blood fats at the start, after 12 weeks, then every 5 years
Clinical summaryFor health professionals
- First-episode trial (EUFEST, Kahn 2008, 498 patients): 33% stopped olanzapine within a year, against 72% on haloperidol. Symptom reduction similar across all drugs (about 60%).
- CATIE (Lieberman 2005, 1,493 patients): longest time on treatment, but more weight gain and metabolic change.
- Metabolic: with clozapine, the worst profile of 18 antipsychotics (Pillinger 2020). Weight gain of 7% or more in 64% with long-term use.
- Dose: usually starts at 10 mg once daily; range 5–20 mg. Lower start in older people and in liver or kidney impairment.
- Smoking lowers levels and fluvoxamine or ciprofloxacin raise them (CYP1A2). Contraindicated in narrow-angle glaucoma; not for dementia-related psychosis.
What it is
Olanzapine is a second-generation antipsychotic. It is used to treat schizophrenia and, once symptoms have improved, to keep them from coming back. It is also used for mania in bipolar disorder.1
How it works
Olanzapine blocks receptors for several of the brain’s chemical messengers at once: dopamine, serotonin, acetylcholine, histamine and noradrenaline. It binds more strongly to the serotonin 5-HT2 receptor than to the dopamine D2 receptor, the main target of older antipsychotics. In brain scans after a single dose, it occupied more serotonin 5-HT2A receptors than dopamine D2 receptors.1
Its effects on blood sugar and blood fats are among the strongest of any antipsychotic.2 Across 100 trials of 18 antipsychotics, greater improvement in symptoms went together with greater increases in weight and cholesterol.2
History
Olanzapine was approved across the European Union in September 1996.1 Two large trials later compared it with other antipsychotics in everyday practice. In the United States, the CATIE trial followed 1,493 people for up to 18 months.3 In Europe, the EUFEST trial followed 498 people with a first episode of schizophrenia, at 50 sites in 14 countries, for a year.4
How well it works
| Outcome | Stopped their medicine |
|---|---|
| Olanzapine | 33 |
| Amisulpride | 40 |
| Ziprasidone | 45 |
| Quetiapine | 53 |
| Haloperidol | 72 |
In EUFEST, people stayed on olanzapine longer than on the other medicines. Yet symptoms fell by about 60 in 100 in every group. The trial was open: patients and doctors knew which medicine was being taken.4
In CATIE, most people stopped their assigned medicine within 18 months: 64 in 100 on olanzapine, and 74 to 82 in 100 on the others. People stayed on olanzapine longer, but it caused more weight gain and more change in blood sugar and blood fats.3
For antipsychotics in general, across 167 placebo-controlled trials, about 51 in 100 people improved at least a little, against 30 in 100 on placebo. About 23 in 100 improved a lot, against 14 in 100.5
In blinded trials in treatment-resistant schizophrenia, olanzapine often did about as well as clozapine.6 To prevent relapse, trials found no clear difference between antipsychotics, so the choice depends mainly on side effects.7
Side effects
| How common | Side effects |
|---|---|
| Very common: more than 1 in 10 people | Weight gain; sleepiness; raised prolactin, a hormone; dizziness or fainting on standing up, early in treatment |
| Common: 1 in 100 to 1 in 10 | Raised cholesterol, blood fats and blood sugar; increased appetite; dizziness; restlessness, stiffness, tremor and unusual movements; constipation and dry mouth; raised liver enzymes; rash; joint pain; tiredness; swollen ankles; fever; erection problems and lower sex drive; fewer white blood cells |
| Uncommon: 1 in 1,000 to 1 in 100 | Diabetes, occasionally with a dangerous rise in blood sugar; seizures, mostly in people with a history of them; tardive dyskinesia, lasting involuntary movements; muscle spasms; slow heartbeat; blood clots; sensitivity to sunlight; hair loss; trouble passing or holding urine; missed periods, breast enlargement or milk from the breasts |
| Rare: 1 in 10,000 to 1 in 1,000 | Neuroleptic malignant syndrome, a reaction with high fever and stiff muscles; inflammation of the pancreas or liver; muscle breakdown; dangerous heart rhythms and sudden death; a painful, lasting erection |
The side effects above are from the European product information.1 Three need particular attention:
- Weight. With a year or more of treatment, 64 in 100 people gained at least 7 in 100 of their body weight, 32 in 100 at least 15 in 100, and 12 in 100 a quarter or more.1 Among 18 antipsychotics, olanzapine and clozapine had the worst effects on weight, blood sugar and blood fats.2
- Blood sugar. Diabetes can develop or worsen, occasionally with ketoacidosis or coma, and in some cases it has been fatal. Weight gain sometimes came first. Signs of high blood sugar include great thirst, passing a lot of urine, hunger and weakness.1
- Prolactin. In trials of up to 12 weeks, prolactin rose above normal in about 30 in 100 people, usually only mildly.1
Get medical help straight away for pain, swelling and redness in a leg, or chest pain and difficulty breathing, which can be signs of a blood clot; a combination of fever, faster breathing, sweating, stiff muscles and drowsiness; or unusual movements, mainly of the face or tongue.1
Side effects can be reported to Lareb, the Dutch side-effects centre, to the FAMHP in Belgium, or to the manufacturer.
Administration
Olanzapine tablets are taken once a day, with or without food. The prescriber adjusts the dose to how the person responds, and may start lower in older people and in people with liver or kidney problems.1 A short-acting injection is used to calm severe agitation quickly when tablets are not possible.1 A long-acting injection is described under long-acting injections (opens in a new tab).
The product information advises checking weight at the start, after 4, 8 and 12 weeks, and then every 3 months; blood sugar at the start, after 12 weeks and then yearly; and blood fats at the start, after 12 weeks and then every 5 years. In people over 65, blood pressure is checked from time to time.1
Contraindications and cautions
Olanzapine is not used in people at known risk of narrow-angle glaucoma.1
It is not recommended for psychosis or behaviour problems in dementia. In trials in older people with dementia, deaths were about twice as common as on placebo, 3.5 in 100 against 1.5 in 100, and strokes three times as common. It is also not recommended for psychosis in Parkinson’s disease, where it worsened movement symptoms.1
Care is needed in people with diabetes or its risk factors, an enlarged prostate, a paralysed bowel, liver disease, low white blood cells, seizures, heart rhythm problems, or a risk of blood clots. White blood cells fell more often when olanzapine was combined with valproate, an epilepsy medicine.1
Smoking speeds up the breakdown of olanzapine, so stopping or starting smoking can change its level in the blood. The antidepressant fluvoxamine and the antibiotic ciprofloxacin slow its breakdown. Alcohol adds to the sleepiness.1
There is limited experience in pregnancy, so olanzapine is used only if the benefit justifies the risk, and babies exposed late in pregnancy are watched after birth. Breastfeeding is not advised. Because it can cause sleepiness and dizziness, care is needed when driving. It is not recommended for people under 18.1
Check the patient leaflet, and ask the prescriber about your own situation.
Stopping
Olanzapine is reduced gradually when it is stopped. Stopping suddenly has rarely caused sweating, sleeplessness, tremor, anxiety, nausea or vomiting.1 Across 30 trials with 4,249 people, 24 in 100 people who stayed on an antipsychotic relapsed within 7 to 12 months, against 61 in 100 who switched to placebo.8 Changes are best planned with the prescriber.
Alternatives
When weight gain or changes in blood sugar are a problem, aripiprazole, brexpiprazole, cariprazine, lurasidone and ziprasidone had the mildest effects on metabolism.2 See aripiprazole (opens in a new tab). When two antipsychotics have not helped enough, the next step is clozapine (opens in a new tab). Alongside medicine, NICE recommends CBT for psychosis (opens in a new tab) and family intervention (opens in a new tab).9
What we don’t know yet
- Why the antipsychotics that help most also tend to cause the most weight gain.
- How best to prevent the weight gain.
- How to tell in advance who will do best on olanzapine rather than another antipsychotic.
