Olanzapine, sold as Zyprexa, has been one of the most widely prescribed antipsychotics in the world since its FDA approval in 1996. It's used for both schizophrenia and bipolar disorder, comes in oral and long-acting injectable forms, and is widely considered one of the more effective second-generation antipsychotics. It also has one of the most significant weight gain profiles of any commonly used antipsychotic — a tradeoff that needs to be discussed honestly before starting.
Olanzapine is a highly effective antipsychotic with a strong evidence base — but its metabolic side effects (weight gain, diabetes risk) are significant and warrant careful planning.
What olanzapine is
Olanzapine is a "thienobenzodiazepine" — chemically related to clozapine, with a similar broad-spectrum receptor activity. It blocks several serotonin and dopamine receptors, plus histamine, muscarinic, and adrenergic receptors. The histamine and serotonin effects contribute to its sedation and weight gain profile; the dopamine D2 blockade drives its antipsychotic effect.
What it treats
- Schizophrenia — both acute episodes and long-term maintenance
- Bipolar I disorder — acute mania and maintenance
- Treatment-resistant depression (combined with fluoxetine, sold as Symbyax)
- Off-label uses include severe agitation, anorexia nervosa adjunct, chemotherapy-induced nausea
How it's typically dosed
- Schizophrenia: usually 10–20 mg/day, sometimes higher in resistant cases
- Bipolar mania: typically started at 10–15 mg/day
- Maintenance: 5–20 mg/day
Most patients take it once a day, often at bedtime to take advantage of its sedating effect. There's also a fast-dissolving oral form (Zyprexa Zydis) and a long-acting injection (Zyprexa Relprevv) given every 2 or 4 weeks.
The long-acting injection
Olanzapine LAI (Zyprexa Relprevv) has a small but real risk of "post-injection delirium/sedation syndrome" — a confusing, sedating reaction that can occur in the hours after an injection. Because of this, every patient receiving it must stay at the clinic for at least 3 hours of monitoring after each injection. This is logistically inconvenient, so olanzapine LAI is less commonly used than other LAIs.
How effective it is
Olanzapine is consistently rated among the most effective antipsychotics in network meta-analyses (Leucht et al., Lancet 2013), often second only to clozapine for overall effect on positive symptoms. It is particularly useful for patients with prominent agitation or insomnia accompanying their psychosis.
The downsides
Weight gain
This is the most important conversation to have before starting olanzapine. Average weight gain in the first year is about 5–8 kg (11–18 lbs) — though some patients gain much more. The weight gain is driven by appetite increase, slower metabolism, and food cravings, particularly for carbohydrates.
Metabolic effects
Olanzapine increases the risk of:
- Type 2 diabetes (sometimes appearing within months)
- High triglycerides and cholesterol
- Insulin resistance independent of weight gain
The American Diabetes Association recommends baseline labs and follow-up monitoring for any patient starting olanzapine.
Sedation
Common, especially in the first weeks. Often manageable by taking the dose at night.
Who it's a good fit for
Olanzapine often works well for:
- Patients with severe positive symptoms not controlled by other antipsychotics
- Patients with significant insomnia or agitation accompanying psychosis
- Patients who have responded to it before
- Patients with bipolar mania who need rapid stabilisation
Who might want to choose differently
- Patients with diabetes or strong family history of diabetes
- Patients who are particularly concerned about weight gain
- Patients with significant cardiovascular risk factors
Alternatives include aripiprazole, lurasidone, ziprasidone, and brexpiprazole — all generally lighter on metabolic effects, though sometimes less effective for severe symptoms.
The Symbyax combination
Olanzapine combined with fluoxetine (an SSRI) is sold as Symbyax for treatment-resistant depression and depressive episodes in bipolar disorder. The combination has stronger evidence than either drug alone for these specific indications.
Discontinuation
Olanzapine should not be stopped abruptly. Discontinuation symptoms can include nausea, insomnia, anxiety, and cholinergic rebound (sweating, drooling). Tapering over weeks to months is the standard approach, in coordination with a prescriber.
This article is for educational purposes only and is not medical advice. Information is summarised from publicly available FDA labelling. Always consult your prescribing clinician before starting, stopping, or changing any medication.