What is the therapeutic dosing regimen of Zyprexa (olanzapine) for adults with schizophrenia or bipolar I disorder, including acute mania and elderly patients?

Therapeutic Dosing of Zyprexa (Olanzapine)

Adult Schizophrenia

For adults with schizophrenia, start olanzapine at 5–10 mg once daily and titrate to a target range of 10–20 mg/day, with most patients responding optimally at 10–15 mg/day. 1

• Initial dosing: Begin with 5–10 mg once daily without regard to meals 1
• Titration schedule: Increase in 5 mg increments at intervals of not less than 24 hours if clinically indicated 1
• Target therapeutic range: 10–20 mg/day, with the majority of patients achieving optimal response at 10–15 mg/day 1, 2
• Maximum recommended dose: 20 mg/day for routine clinical use; doses above 20 mg/day have not been systematically evaluated in controlled trials 1

Treatment-Resistant Cases

• For treatment-refractory schizophrenia not responding to standard doses (up to 20 mg/day), some patients may benefit from higher doses of 35–60 mg/day, which have been reported as well-tolerated in case series 3
• Critical caveat: High-dose olanzapine (>20 mg/day) is off-label and should only be considered after failure of at least two adequate trials of other antipsychotics, including clozapine consideration 3

Maintenance Therapy

• Continue the effective acute-phase dose (typically 10–20 mg/day) for long-term maintenance 1
• Olanzapine significantly reduces one-year relapse risk to 19.6–28.6% compared to 45.5–69.9% with placebo or ineffective dosing 4
• Periodically reassess the need for continued treatment and the lowest effective maintenance dose 1

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Bipolar I Disorder – Adults

For acute mania in adults, initiate olanzapine at 10–15 mg once daily and adjust within the 5–20 mg/day range based on response, with most patients stabilizing at 10–15 mg/day. 1

Monotherapy for Acute Mania

• Starting dose: 10 or 15 mg once daily without regard to meals 1
• Dose adjustments: Make changes in 5 mg increments at intervals of at least 24 hours 1
• Therapeutic range: 5–20 mg/day demonstrated efficacy in 3–4 week controlled trials 1
• Typical effective dose: 10–15 mg/day provides rapid and substantial symptomatic control 5, 6

Adjunctive Therapy with Lithium or Valproate

• Initial dose: 10 mg once daily when combined with lithium or valproate 1
• Therapeutic range: 5–20 mg/day in combination studies 1
• Combination therapy (olanzapine plus lithium or valproate) is superior to mood stabilizer monotherapy for severe mania 5, 6

Maintenance Monotherapy

• Dose range: 5–20 mg/day for relapse prevention after achieving response (typically after 2 weeks of stability) 1
• Olanzapine is the only atypical antipsychotic FDA-approved for maintenance therapy in bipolar I disorder 5, 6
• Olanzapine demonstrates superior efficacy versus lithium in preventing manic relapse, though not depressive relapse 5, 6

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Bipolar I Disorder – Adolescents (Ages 13–17)

For adolescents with bipolar I disorder, start olanzapine at 2.5–5 mg once daily and titrate to a target of 10 mg/day, with a flexible range of 2.5–20 mg/day based on response. 1

• Starting dose: 2.5 or 5 mg once daily 1
• Target dose: 10 mg/day 1
• Dose adjustments: Increase or decrease in 2.5 or 5 mg increments as needed 1
• Therapeutic range: 2.5–20 mg/day (mean modal dose 10.7 mg/day in trials) 1
• Maximum evaluated dose: 20 mg/day; safety and efficacy above this dose have not been established 1

Maintenance in Adolescents

• Continue at the lowest dose needed to maintain remission after acute response 1
• Maintenance efficacy in adolescents is extrapolated from adult data and pharmacokinetic comparisons 1
• Periodically reassess the need for ongoing treatment 1

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Acute Agitation (Intramuscular Formulation)

For acute agitation in schizophrenia or bipolar I mania, administer 10 mg IM olanzapine as the initial dose, with consideration of 5–7.5 mg when clinical factors warrant lower dosing. 1

Standard IM Dosing

• Recommended initial dose: 10 mg IM 1
• Lower-dose option: 5 or 7.5 mg IM when clinical factors (e.g., debilitation, hypotension risk, pharmacodynamic sensitivity) warrant 1
• Repeat dosing: If agitation persists, subsequent doses up to 10 mg may be given, but efficacy of repeated doses has not been systematically evaluated 1
• Dosing intervals: Minimum 2 hours after the first dose and 4 hours after the second dose 1
• Maximum daily dose: 30 mg total; doses exceeding 30 mg/day or more frequent than the specified intervals have not been evaluated 1

Special Populations (IM)

• Geriatric patients: 5 mg/injection 1
• Debilitated or hypotension-prone patients: 2.5 mg/injection 1

Critical Safety Consideration

• Maximal IM dosing (e.g., three 10 mg doses given 2–4 hours apart) is associated with substantial orthostatic hypotension risk 1
• Assess for orthostatic hypotension before administering subsequent IM doses 1
• Do not administer additional IM olanzapine to patients with clinically significant postural blood pressure changes 1

Transition to Oral Therapy

• Initiate oral olanzapine at 5–20 mg/day as soon as clinically appropriate after IM stabilization 1

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Elderly Patients

• Lower starting doses are appropriate: Consider 5 mg/day orally or 5 mg IM for acute agitation 1
• Elderly patients may be more sensitive to olanzapine's pharmacodynamic effects, requiring dose reduction 1

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Key Monitoring and Safety Points

• Weight gain is the most common adverse effect and occurs more frequently with olanzapine than most other atypical antipsychotics 5, 6, 2
• Metabolic monitoring: Baseline and periodic assessment of weight, glucose, and lipids is essential 7
• Extrapyramidal symptoms (EPS): Olanzapine has a low incidence of EPS compared to typical antipsychotics and risperidone 5, 6, 2
• Avoid combining high-dose olanzapine with benzodiazepines: Fatalities have been reported with concurrent use 7
• Olanzapine does not cause clinically significant hyperprolactinemia or QT prolongation 2

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Common Pitfalls to Avoid

• Underdosing: Starting at 5 mg/day may be insufficient for acute mania; 10–15 mg/day is typically required for robust antimanic effect 1, 5
• Premature dose escalation: Allow at least 24 hours between dose adjustments to assess response 1
• Exceeding 20 mg/day without justification: Doses above 20 mg/day lack systematic safety and efficacy data in controlled trials 1
• Inadequate trial duration: Assess response after 4–6 weeks at therapeutic doses before concluding treatment failure 8
• Neglecting metabolic monitoring: Failure to monitor weight, glucose, and lipids can lead to significant metabolic complications 7