What is the recommended use and dosage of Olanzapine (atypical antipsychotic) for treating schizophrenia and bipolar disorder?

Olanzapine for Schizophrenia and Bipolar Disorder

Recommended Dosing

For schizophrenia in adults, start olanzapine at 5-10 mg once daily with a target dose of 10 mg/day within several days; for bipolar I disorder manic or mixed episodes in adults, start at 10-15 mg once daily. 1

Schizophrenia Dosing

Adults:

• Initial dose: 5-10 mg once daily orally 1
• Target dose: 10 mg/day, achieved within several days 1
• Alternative initial target dose of 7.5-10 mg/day is supported by early psychosis guidelines 2

Adolescents (ages 13-17):

• Initial dose: 2.5-5 mg once daily orally 1
• Target dose: 10 mg/day 1
• Adolescents have increased potential for weight gain and dyslipidemia compared to adults, which should influence prescribing decisions 1

Bipolar I Disorder Dosing

Adults - Manic or Mixed Episodes:

• Initial dose: 10 or 15 mg once daily orally 1
• When used as adjunct to lithium or valproate: start at 10 mg once daily 1

Adolescents (ages 13-17) - Manic or Mixed Episodes:

• Initial dose: 2.5-5 mg once daily orally 1
• Target dose: 10 mg/day 1

Bipolar Depression (in combination with fluoxetine):

• Adults: Start at 5 mg olanzapine + 20 mg fluoxetine once daily 1
• Adolescents: Start at 2.5 mg olanzapine + 20 mg fluoxetine once daily 1
• Maximum evaluated safety: 18 mg olanzapine with 75 mg fluoxetine in adults; 12 mg olanzapine with 50 mg fluoxetine in adolescents 1

Acute Agitation Management

For acute agitation in schizophrenia or bipolar mania, administer 10 mg intramuscular olanzapine (or 5-7.5 mg when clinically warranted), with assessment for orthostatic hypotension before subsequent dosing. 1

• Maximum 3 doses given 2-4 hours apart 1
• Alternative dosing for delirium in cancer patients: 2.5-5 mg PO or SC, which may cause drowsiness and orthostatic hypotension 2, 3

Treatment Algorithm for Schizophrenia

First-Line Treatment:

• Initiate olanzapine at therapeutic dose for minimum 4 weeks with good adherence 2
• If significant positive symptoms persist, switch to alternative antipsychotic with different pharmacodynamic profile 2

Second-Line Options:

• For patients who started with D2 partial agonist, consider switching to amisulpride, risperidone, paliperidone, or olanzapine (with samidorphan combination or concurrent metformin) 2
• Olanzapine/samidorphan (OLZ/SAM) combination provides olanzapine efficacy while reducing weight gain risk by approximately 50% at 24 weeks 4

Treatment-Resistant Cases:

• After failure of two first-line atypical antipsychotics (approximately 12 weeks each), reassess diagnosis and consider clozapine trial 2
• Clozapine should be offered with concomitant metformin to attenuate weight gain 2

Special Populations

Elderly or Debilitated Patients:

• Lower starting doses recommended 1
• Critical Warning: Elderly patients with dementia-related psychosis have increased risk of death; olanzapine is NOT approved for this indication 1

Patients with Hepatic Impairment:

• Reduce dose in patients with hepatic impairment 2

First-Episode Psychosis:

• Initial target doses: 7.5-10 mg/day 2
• Dose increases should occur only at widely spaced intervals (14-21 days after initial titration) if response inadequate 2

Monitoring Requirements

Before initiating treatment, obtain: 2

• BMI, waist circumference, blood pressure
• HbA1c, fasting glucose, lipids
• Prolactin, liver function tests, urea and electrolytes
• Full blood count, electrocardiogram

Follow-up monitoring: 2

• Fasting glucose at 4 weeks
• BMI, waist circumference, blood pressure weekly for 6 weeks
• Repeat all measures at 3 months, then annually

Critical Safety Considerations

Metabolic Effects:

• Weight gain and metabolic syndrome are significant concerns requiring clinician vigilance 5
• Olanzapine-treated adolescents experience greater increases in bodyweight, sedation, blood lipids, serum prolactin, and liver transaminases compared to adults 6
• Consider switching to antipsychotic with more benign metabolic profile, adding metformin, or adding GLP-1 receptor agonist if metabolic complications develop 2

Contraindications with Opioids:

• OLZ/SAM formulation is contraindicated in patients using opioids or undergoing acute opioid withdrawal due to samidorphan component 4

Drug Interactions:

• Avoid combining with metoclopramide, phenothiazines, or haloperidol to prevent excessive dopamine blockade 3
• Caution: Fatalities reported with concurrent high-dose olanzapine and benzodiazepines 2

Extrapyramidal Symptoms:

• Olanzapine has significantly fewer extrapyramidal symptoms than haloperidol and risperidone 7
• If akathisia develops, consider dose reduction, switch to quetiapine, or add propranolol 10-30 mg two to three times daily 2

Efficacy Evidence

Comparative Effectiveness:

• Olanzapine demonstrates superior efficacy to haloperidol for overall psychopathology, depressive symptoms, and negative symptoms 7
• One-year relapse risk (rehospitalization) significantly lower with olanzapine versus haloperidol 7
• In bipolar mania, olanzapine shows equal or superior efficacy to valproate and superior efficacy when combined with lithium or valproate versus mood stabilizer monotherapy 5

Administration:

• May be given without regard to meals 1
• Available as standard tablets, orally disintegrating tablets, and intramuscular injection 1