- Atypical Antipsychotic (Second Generation agent)
- Neuroleptic
- Thienobenzodiazepine
- Primarily Serotonin Type II Antagonist (5-HT2 Antagonist - 5-HT2A and 5-HT2C, as well as 5-HT3)
- Also Dopamine (D1-4), muscarinic (M1-5) Anticholinergic, adrenergic (alpha-1) and Histamine (H1) Antagonist
- Chemical structure similar to Clozapine
- Primary Indications
- Schizophrenia
- Acute mania phase of Bipolar Disorder
- Agitated Delirium (emergency department)
- Bipolar Depression
- Combine with Fluoxetine or other Antidepressant
- Other Indications
- Obsessive Compulsive Disorder
- Combine with Antidepressant (esp. SSRI)
- Acute Migraine Headache
- Appears to have similar efficacy to Droperidol (Inapsine) for Migraine Headache
- Hill (2008) Acad Emerg Med 15(9):806-11 +PMID:19244630 [PubMed]
- Obsessive Compulsive Disorder
- Avoid use in Psychosis in Dementia
- See Agitation in Dementia
- See Psychosis in Dementia
- Higher risk of CVA and overall mortality in elderly
- Sultzer (2008) Am J Psychiatry 165(7): 844-54 [PubMed]
- Olanzapine (Zyprexa)
- Standard preparation, and generic ($30/month)
- Olanzapine/Samidorphan (Lybalvi)
- Released in 2021 at $1400/month
- Samidorphan is a Naltrexone derivative added to reduce weight gain that typically occurs with Olanzapine
- Avoid all Opioids while on Samidorphan (and causes withdrawal in those on Chronic Opioids)
- Transition to Olanzapine without Samidorphan at least 5 days before Opioid management needed
- Marginal efficacy for cost (other strategies to reduce weight gain are preferred)
- Consider Antipsychotics less associated with weight gain (e.g. Aripiprazole, Ziprasidone)
- Lifestyle changes (Exercise and diet)
- Consider Metformin
- References
- (2022) Presc Lett 29(1): 6
- Adult Oral Dosing
- Start: 5 to 10 mg orally daily (may be repeated every 2 hours to total maximum of 20 mg/day)
- Increase in 5 mg increments weekly as tolerated
- Maximum: 20 mg/day
- Elderly Oral Dosing
- Initial: 1.25 to 2.5 mg orally daily
- Titrate up as tolerated (watch for Hypotension)
- Maximum: 10 mg/day
- Child Oral Dosing (age 13 to 17 years old)
- Start 2.5 to 5 mg orally daily
- May increase by 2.5 to 5 mg/day to target dose of 10 mg orally daily
- Maximum: 20 mg/day
- Adult Long Acting Intramuscular Injection
- Olanzapine XR 150 to 300 mg deep gluteal IM every 2 weeks (or 300 to 405 mg deep IM every 4 weeks)
- Base dose on prior oral dosing
- Acute Agitation
- Acute management of Agitation (Psychosis, acute bipolar mania or Schizophrenia)
- Dose: 5 to 10 mg IM every 4 hours (up to 30 mg/day)
- May also use 5-10 mg orally every 4 hours (up to 20 mg/day)
- IM Dosing schedule may also be increased (maximum total 30 mg/day)
- Dose 1 at time 0 hours: 10 mg
- Dose 2 at time 2 hours: 10 mg
- Dose 3 at time 6 hours: 10 mg (last dose for day)
- Dose: 5 to 10 mg IM every 4 hours (up to 30 mg/day)
- Emerging: Intravenous dosing in Agitation
- Off label use (Only FDA approved for oral and IM delivery)
- Use only in closely monitored settings (respiratory depression, Hypotension)
- Initial Dose: 5 mg IV
- Subsequent dose: 2.5 to 5 mg IV at least 10 minutes after initial dose (maximum 10 mg/day)
- Large HCMC ED study in 2016 demonstrated safety of 5 mg IV doses
- No serious complications including no QT Prolongation (although Hypoxia did occur)
- Martel (2016) Acad Emerg Med 23(1): 29-35 +PMID:26720055 [PubMed]
- See Antipsychotics
- Weight gain (4 kg)
- Sedation
- Headache
- Orthostatic Hypotension (21% with oral dosing, even higher risk with IM dosing)
- Seizures (nearly 1% of patients)
- Extrapyramidal Side Effects
- Akathisia (27%)
- Cognitive slowing
- Overall higher mortality in elderly (see Atypical Antipsychotics)
- Lowest risk of QTc Prolongation compared with other Antipsychotics
- Bradycardia, Hypotension and hypoventilation may occur with IM dosing (esp. when combined with Benzodiazepines)
-
Hyperglycemia
- Increased risk of Diabetes Mellitus
- Koro (2002) BMJ 325:243-5 [PubMed]
- Hyperlipidemia
- Other effects
- Neuroleptic malignant sydnrome (rare, but lethal)
- Increased Liver Function Tests
- Increased Creatine Kinase
- Pancreatitis
- Anticholinergic side effects
- Hyperprolactinemia (secondary reproductive function disorders)
- Increase Antipsychotic levels (toxicity risk): Monitor for toxicity
- Decrease Antipsychotic levels (lower efficacy)
- Cardiorespiratory depression (includes sedation, Bradycardia and Hypotension)
- Benzodiazepines (e.g. Midazolam)
- Based on warning in prescribing information since 2005
- Combination appears safe from studies in which Olanzapine was combined with Benzodiazepines
- EMA recommends separating dosing by 60 minutes
- Williams (2018) Ment Health Clin 8(5): 208–213 +PMID: 30206503 [PubMed]
- Benzodiazepines (e.g. Midazolam)
- Pregnancy Category C
- However, does cross placenta
- Not recommended during Lactation (found in Breast Milk)
- See Antipsychotic
- (2016) Med Lett Drugs Ther 58(1510): 160-5
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 42-3
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27
- LoVecchio (2021) Crit Dec Emerg Med 35(9): 31