Olanzapine

Aka: Olanzapine, Zyprexa

1. Class
   1. Atypical Antipsychotic (Second Generation agent)
   2. Neuroleptic
   3. Thienobenzodiazepine
2. Mechanism
   1. Primarily Serotonin Type II Antagonist (5-HT2 antagonist)
   2. Also Dopamine, muscarinic Anticholinergic, alpha-1 and histamine H1 antagonist
   3. Chemical structure similar to Clozapine
3. Indications
   1. Primary Indications
      1. Schizophrenia
      2. Acute mania phase of Bipolar Disorder
      3. Agitated Delirium (emergency department)
   2. Other Indications
      1. Migraine Headache
         1. Appears to have similar efficacy to Droperidol (Inapsine) for Migraine Headache
         2. Hill (2008) Acad Emerg Med 15(9):806-11 +PMID:19244630 [PubMed]
   3. Avoid use in Psychosis in Dementia
      1. Higher risk of CVA and overall mortality in elderly
4. Dosing
   1. Adults
      1. Start: 5 to 10 mg orally daily
      2. Increase in 5 mg increments weekly as tolerated
      3. Maximum: 20 mg/day
   2. Elderly
      1. Initial: 1.25 to 2.5 mg PO qd
      2. Titrate up as tolerated (watch for Hypotension)
      3. Maximum: 10 mg/day
   3. Acute management of Agitation
      1. Dose: 10 mg IM every 4 hours (up to 30 mg/day)
   4. Emerging: Intravenous dosing
      1. Only FDA approved for oral and IM delivery
      2. Large HCMC ED study in 2016 demonstrated safety of IV doses (typically 5 mg)
         1. No serious complications including no QT Prolongation (although Hypoxia did occur)
         2. Martel (2016) Acad Emerg Med 23(1): 29-35 +PMID:26720055 [PubMed]
5. Adverse Effects
   1. See Antipsychotics
   2. Weight gain (4 kg)
   3. Sedation
   4. Orthostatic Hypotension
   5. Seizures (nearly 1% of patients)
   6. Overall higher mortality in elderly
   7. Lowest risk of QTc Prolongation compared with other Antipsychotics
   8. Hyperglycemia
      1. Increased risk of Diabetes Mellitus
      2. Koro (2002) BMJ 325:243-5 [PubMed]
   9. Hyperlipidemia
      1. Koro (2002) Arch Gen Psychiatry 59:1021-6 [PubMed]
   10. Other effects
       1. Neuroleptic malignant sydnrome (rare, but lethal)
       2. Extrapyramidal Side Effects
       3. Increased Liver Function Tests
       4. Increased Creatine Kinase
       5. Pancreatitis
       6. Anticholinergic side effects
6. Drug Interactions
   1. Increase Antipsychotic levels (toxicity risk): Monitor for toxicity
      1. Ciprofloxacin
      2. Fluvoxamine
   2. Decrease Antipsychotic levels (lower efficacy)
      1. Carbamazepine
      2. Phenytoin
      3. Nicotine
      4. Rifampin
      5. Omeprazole
   3. Cardiorespiratory depression (includes sedation, Bradycardia and Hypotension)
      1. Benzodiazepines (e.g. Midazolam)
         1. Based on warning in prescribing information since 2005
         2. Combination appears safe from studies in which Olanzapine was combined with Benzodiazepines
         3. EMA recommends separating dosing by 60 minutes
         4. Williams (2018) Ment Health Clin 8(5): 208–213 +PMID: 30206503 [PubMed]
            1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125121/
7. Safety
   1. Pregnancy Category C
   2. Not recommended during Lactation (found in Breast Milk)
8. Monitoring
   1. See Antipsychotic
9. References
   1. Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27