Is it safe to increase the dose of Zyprexa (olanzapine) from 10mg to 20mg in an adult patient with psychosis, schizophrenia, or bipolar disorder?

Increasing Zyprexa from 10mg to 20mg in Bipolar Disorder and Psychosis

Yes, you can safely increase Zyprexa (olanzapine) from 10mg to 20mg, as this falls within the FDA-approved therapeutic range for bipolar disorder and schizophrenia, with doses of 5-20mg/day demonstrating efficacy in clinical trials. 1

FDA-Approved Dosing Guidelines

For adults with bipolar I disorder (manic or mixed episodes), the FDA recommends starting olanzapine at 10-15mg daily, with dosage adjustments of 5mg occurring at intervals of not less than 24 hours. 1

• Short-term antimanic efficacy was demonstrated in the dose range of 5-20mg/day in clinical trials 1
• The safety of doses above 20mg/day has not been evaluated in FDA registration trials 1
• When administered as adjunctive treatment to lithium or valproate, olanzapine dosing should generally begin with 10mg once daily, with efficacy demonstrated in the 5-20mg/day range 1

Evidence Supporting Dose Escalation to 20mg

Olanzapine 10-20mg/day demonstrates superior efficacy compared to lower doses for acute mania and psychotic symptoms. 2

• In controlled trials, olanzapine 5-20mg/day was significantly superior to haloperidol in overall improvements in psychopathology rating scales and treatment of depressive and negative symptoms 2
• The 1-year risk of relapse (rehospitalization) was significantly lower with olanzapine than haloperidol treatment 2
• Olanzapine 10-20mg/day combined with lithium or valproate was superior to mood stabilizers alone for acute mania in bipolar disorder 3

Clinical Decision Algorithm

Increase olanzapine from 10mg to 20mg when:

• Current symptoms remain inadequately controlled after at least 24 hours at 10mg 1
• The patient has severe agitation, psychotic symptoms, or treatment-resistant mania requiring more aggressive dosing 3
• The patient is tolerating 10mg without significant adverse effects, particularly excessive sedation or metabolic complications 2

The dose increase should occur in 5mg increments at intervals of not less than 24 hours. 1

Important Safety Considerations and Monitoring

Metabolic monitoring is essential when increasing olanzapine dose, as higher doses are associated with greater weight gain and metabolic effects. 3, 2

• Baseline monitoring should include BMI, waist circumference, blood pressure, fasting glucose, and fasting lipid panel 3
• Follow-up monitoring: BMI monthly for 3 months then quarterly; blood pressure, glucose, and lipids at 3 months then yearly 3
• The most common adverse effects with olanzapine are weight gain, somnolence, dizziness, anticholinergic effects (constipation and dry mouth), and transient asymptomatic liver enzyme elevations 2

Olanzapine is associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone, and does not cause clinically significant hyperprolactinemia or QT prolongation. 2

Doses Above 20mg: When to Consider

While the FDA-approved maximum is 20mg/day, some treatment-resistant patients may benefit from higher doses (up to 40-60mg/day), though this is off-label. 4, 5

• Case reports describe successful treatment of resistant schizophrenic patients with olanzapine 35-60mg/day without significant side effects 4
• Double-blind trials suggest doses greater than 20mg/day may help selected patients who are treatment-resistant or have high levels of psychopathology 5
• However, doses of 40mg/day are associated with increased risk of weight gain and elevated prolactin compared to 20mg/day 5

Common Pitfalls to Avoid

Do not increase olanzapine more frequently than every 24 hours, as this does not allow adequate time to assess response and increases risk of excessive sedation. 1

• Avoid combining olanzapine with benzodiazepines at high doses, as fatalities have been reported with concurrent use of benzodiazepines with high-dose olanzapine 6
• Do not exceed 20mg/day without clear documentation of treatment resistance at standard doses and careful risk-benefit assessment 1, 5
• Ensure systematic medication trials of 6-8 weeks at adequate doses before concluding olanzapine is ineffective at a given dose 3

Maintenance Therapy Considerations

Once acute symptoms are controlled, continue the effective dose for at least 12-24 months to prevent relapse. 3

• The benefit of maintaining bipolar I patients on olanzapine monotherapy at 5-20mg/day after achieving responder status was demonstrated in controlled trials 1
• Premature discontinuation of maintenance therapy leads to high relapse rates, with withdrawal of effective medications associated with relapse in over 90% of noncompliant patients 3
• Periodically reevaluate the long-term usefulness of olanzapine for the individual patient, potentially adjusting to the lowest dose needed to maintain remission 1