Olanzapine Stats & Data
CN1CCN(CC1)C1=Nc2ccccc2Nc2sc(C)cc12KVWDHTXUZHCGIO-UHFFFAOYSA-NPharmacology
DrugBankDescription
Olanzapine is a thienobenzodiazepine classified as an atypical or second-generation antipsychotic agent. The second-generation antipsychotics were introduced in the 90s and quickly gained traction due to their impressive efficacy, reduced risk for extrapyramidal side effects and reduced susceptibility to drug-drug interactions. Olanzapine very closely resembles clozapine and only differs by two additional methyl groups and the absence of a chloride moiety. It was discovered by scientists at Eli Lilly and approved to be marketed in the US in 1996.
Mechanism of Action
The activity of olanzapine is achieved by the antagonism of multiple neuronal receptors including the dopamine receptor D1, D2, D3 and D4 in the brain, the serotonin receptors 5HT2A, 5HT2C, 5HT3 and 5HT6, the alpha-1 adrenergic receptor, the histamine receptor H1 and multiple muscarinic receptors. As abovementioned, olanzapine presents a wide profile of targets, however, its antagonistic effect towards the dopamine D2 receptor in the mesolimbic pathway is key as it blocks dopamine from having a potential action at the post-synaptic receptor. The binding of olanzapine to the dopamine D2 receptors is easily dissociable and hence, it allows for a certain degree of dopamine neurotransmission. On the other hand, olanzapine acts in the serotonin 5HT2A receptors in the frontal cortex in a similar manner than the reported on dopamine D2 receptors. This determined effect allows for a decrease in adverse effects.
Pharmacodynamics
The effect of olanzapine in the D2 receptor is reported to produce the positive effects of this drug such as a decrease in hallucinations, delusions, disorganized speech, disorganized thought, and disorganized behavior. On the other hand, its effect on the serotonin 5HT2A receptor prevents the onset of anhedonia, flat affect, alogia, avolition and poor attention. Based on the specific mechanism of action, olanzapine presents a higher affinity for the dopamine D2 receptor when compared to the rest of the dopamine receptor isotypes. This characteristic significantly reduces the presence of side effects. Clinical trials for the original use of olanzapine demonstrated significant effectiveness in the treatment of schizophrenia and bipolar disorder in adults and acute manic or mixed episodes associated with bipolar disorder in adolescents. The effect of olanzapine on dopamine and serotonin receptors has been suggested to reduce chemotherapy-induced nausea and vomiting as those receptors are suggested to be involved in this process. For this effect, several clinical trials have been conducted and it has been shown that olanzapine can produce a significant increase in total control of nausea and vomiting. In a high-level study of the effect of olanzapine for this condition, a complete response on the delay phase was observed in 84% of the individual and control of emesis of over 80% despite the phase.
Metabolism
Olanzapine is greatly metabolized in the liver, which represents around 40% of the administered dose, mainly by the activity of glucuronide enzymes and by the cytochrome P450 system. From the CYP system, the main metabolic enzymes are CYP1A2 and CYP2D6. As part of the phase I metabolism, the major circulating metabolites of olanzapine, accounting for approximate 50-60% of this phase, are the 10-N-glucuronide and the 4'-N-desmethyl olanzapine which are clinically inactive and formed by the activity of CYP1A2. On the other hand, CYP2D6 catalyzes the formation of 2-OH olanzapine and the flavin-containing monooxygenase (FMO3) is responsible for N-oxide olanzapine. On the phase II metabolism of olanzapine, UGT1A4 is the key player by generating direct conjugation forms of olanzapine.
Absorption
Olanzapine presents a linear pharmacokinetic profile and, after daily administration, it reaches steady-state in about a week. Under the administration of a normal dosage of olanzapine, the steady-state plasma concentration does not seem to exceed 150 ng/ml with an AUC of 333 ng/h/ml. The absorption of olanzapine is not affected by the concomitant administration of food. The pharmacokinetic profile of olanzapine is characterized by reaching peak plasma concentration of 156.9 ng/ml approximately 6 hours after oral administration.
Toxicity
The toxicity symptoms of olanzapine are known to include somnolence, mydriasis, blurred vision, respiratory depression, hypotension, extrapyramidal symptoms and anticholinergic effects. The overdosage effects in children are generally associated with more significant side effects. The maximum registered dosage of olanzapine in clinical trials was of 300 mg and it was reported to present drowsiness and slurred speech. However, on post-marketing surveillance, a wide range of symptoms have been presented including agitation, dysarthria, tachycardia, extrapyramidal symptoms, and reduced consciousness. One case of overdosage-driven death was reported after ingestion of 450 mg of olanzapine. In the cases of acute overdosage, the establishment of adequate oxygenation and ventilation, gastric lavage and administration of activated charcoal with a laxative is recommended. In carcinogenesis studies, olanzapine was showed to present an increase in the incidence of liver hemangiomas and hemangiosarcomas as well as mammary gland adenomas, and adenocarcinomas. On fertility studies, there was solely found impairment in male mating performance and delays in ovulation. There is no evidence of mutagenic, genotoxic potential not adverse events on fertility.
Indication
Olanzapine was initially used orally and intramuscularly for the chronic treatment of schizophrenia in patients over 13 years old and other psychiatric disorders such as bipolar I disorder including mixed or manic episodes. Olanzapine is also indicated, in combination with lithium or valproate for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder in adults. As well, olanzapine is indicated, in combination with fluoxetine for the treatment of episodes of depression associated with bipolar disorder type 1 and treatment-resistant depression in patients over 10 years old. Olanzapine is also approved for the management of psychomotor agitation associated with schizophrenia and bipolar I mania. Schizophrenia is a complex biochemical brain disorder that affects the person's ability to differentiate reality. It is usually observed as the presence of delusions, hallucinations, social withdrawal and disturbed thinking. Bipolar disorder is a mental health condition defined by periods of extreme mood disturbances. It is categorized in different types from which type 1 is known to involve episodes of severe mania and often depression while type 2 presents less severe forms of mania.
Half-life
Olanzapine presents a half-life ranging between 21 to 54 hours with an average half-life of 30 hours.
Protein Binding
Olanzapine is largely bound to plasma proteins and hence, about 93% of the administered dose is bound. The main proteins for binding are albumin and alpha-1 acid glycoprotein.
Elimination
Olanzapine is mainly eliminated through metabolism and hence, only 7% of the eliminated drug can be found as the unchanged form. It is mainly excreted in the urine which represents around 53% of the excreted dose followed by the feces that represent about 30%.
Volume of Distribution
The volume of distribution of olanzapine is reported to be of 1000 liters which indicate a large distribution throughout the body.
Clearance
The mean clearance rate of olanzapine is of 29.4 L/hour however, some studies have reported an apparent clearance of 25 L/h.
Effect Profile
Curated + 60 ReportsStrong sedation with moderate itching/nausea, mild euphoria and pain relief
Tolerance & Pharmacokinetics
drugs.wikiExperience Report Analysis
ErowidDemographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
ErowidEffects aggregated from 60 experience reports (60 Erowid)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 10
Adverse Effects 4
Dose-Response Correlation
How effect frequency changes across dose levels
View data table
| Effect | Threshold (n=37) |
|---|---|
| Sedation | 64.9% |
| Anxiety Suppression | 45.9% |
| Psychosis | 45.9% |
| Stimulation | 29.7% |
| Focus Enhancement | 16.2% |
| Empathy | 16.2% |
| Confusion | 16.2% |
| Euphoria | 16.2% |
| Visual Distortions | 13.5% |
| Auditory Effects | 10.8% |
| Hospital | 10.8% |
| Music Enhancement | 8.1% |
| Nausea | 8.1% |
| Dissociation | 8.1% |
| Muscle Tension | 5.4% |
Dose–Effect Mapping
Experience ReportsHow reported effects shift across dose tiers, based on 60 experience reports.
Limited tier coverage — most reports fall within the Threshold range. Effects at other dose levels may not be represented.
| Effect | Threshold (n=37) | |
|---|---|---|
| sedation | ||
| anxiety suppression | ||
| psychosis | ||
| stimulation | ||
| focus enhancement | ||
| empathy | ||
| confusion | ||
| euphoria | ||
| visual distortions | ||
| auditory effects | ||
| hospital | ||
| music enhancement | ||
| nausea | ||
| dissociation | ||
| muscle tension | ||
| memory suppression | ||
| body high |
Dosage Distribution
Dose distribution from experience reports
Real-World Dose Distribution
62K DosesFrom 74 individual dose entries
Oral (n=65)
Common Combinations
Most co-occurring substances in experience reports
Form / Preparation
Most common forms and preparations reported
Body-Weight Dosing
Dose relative to body weight from reports with weight data
Redose Patterns
Redosing behavior across 50 reports
Harm Reduction
drugs.wikiReasoning for harm‑reduction additions (with sources): 1) Long half‑life means next‑day impairment is plausible; most adults exhibit a 21–54 h elimination half‑life (mean ~30 h), so sedation/cognitive slowing can linger into the following day. Advise against driving, climbing, or operating tools until fully alert. 2) IM olanzapine combined with benzodiazepines has post‑marketing signals of severe cardiorespiratory depression; authoritative summaries advise against parenteral co‑administration. Keep at least an hour separation in clinical settings and avoid DIY IM use. 3) CNS depressant stacking raises overdose risk. Opioids, alcohol, gabapentinoids and sedating antihistamines add respiratory depression and hypotension; several case series show hypoxia and rare airway interventions after parenteral olanzapine, often amid polysubstance use. Keep the person on their side (recovery position), monitor breathing, and call emergency services if difficult to arouse, cyanotic, or with slow/irregular respirations. 4) Smoking status and CYP1A2 modulators change olanzapine exposure: tobacco smoke and carbamazepine can lower levels and reduce effectiveness, while fluvoxamine and ciprofloxacin can increase levels and sedation. Sudden smoking cessation can increase exposure; dose‑sensitivity may rise in non‑smokers. 5) QT risk: meta‑analyses suggest olanzapine has minimal QT prolongation at licensed doses; however, when combined with strong QT‑prolongers or in patients with electrolyte abnormalities, prudence (hydration, K/Mg repletion, ECG if symptomatic) is reasonable. 6) Metabolic harms accumulate with repeated use (weight gain, insulin resistance, dyslipidemia). This argues against frequent ‘trip‑abort’ reliance; prefer non‑pharmacologic de‑escalation first and reserve olanzapine for rare crises. Monitor weight and glucose if usage becomes recurrent. 7) Overdose can mimic opioid toxicity (miosis, respiratory depression, coma). In suspected overdose, prioritize airway/ventilation and seek urgent care; activated charcoal can meaningfully reduce AUC if given early in medical settings. Do not give stimulants to ‘counteract’ sedation. 8) ODT specifics: Zyprexa Zydis disintegrates within seconds and is swallowed; absorption is gastrointestinal. This makes cheeking harder but does not guarantee trans‑mucosal delivery. 9) ‘Trip‑killing’: Community reports describe partial-to-complete attenuation of LSD/psilocybin within ~20–45 min after 5–10 mg PO/ODT, often followed by sleep; responses vary and some report paradoxical anxiety/delirium if taken late or at low doses. Start low (2.5–5 mg) if attempting, have a sober sitter, and avoid stacking sedatives. 10) Masking effect: When used during stimulant or empathogen intoxication, olanzapine may blunt the ‘high’ while not fixing hypertension/hyperthermia; seek medical help rather than assuming safety.
References
Drugs.wiki References
- DrugBank DB00334 monograph
- Clin Pharmacokinet profile (half-life 21–54 h)
- StatPearls: Olanzapine (IM benzo caution; metabolic risks; PK)
- QT with atypical antipsychotics: evidence overview
- Zydis label excerpt (ODT disintegrates within seconds)
- StatPearls: Olanzapine toxicity features (miosis, respiratory depression)
- Bluelight: ‘Olanzapine to end a bad trip’ (community reports)
- Reddit r/LSD: ‘Trip killer Olanzapine’ experience
- Emergency department IV/IM olanzapine cohort (hypoxia uncommon but present)