What is the role of Zyprexa (olanzapine) in the treatment of bipolar disorder?

Role of Olanzapine (Zyprexa) in Bipolar Disorder Treatment

Olanzapine is FDA-approved for the acute treatment of manic or mixed episodes in bipolar I disorder, both as monotherapy and as adjunctive therapy with lithium or valproate, and for maintenance treatment to prevent recurrence in responders, though it should not be first-line due to significant weight gain and metabolic side effects. 1

Indications in Bipolar Disorder

Olanzapine (Zyprexa) has several specific indications in bipolar disorder:

• Acute treatment of manic or mixed episodes in bipolar I disorder
• Maintenance treatment of bipolar I disorder in patients who responded to olanzapine during acute treatment
• Adjunctive therapy with lithium or valproate for manic or mixed episodes
• Treatment of depressive episodes in bipolar I disorder when combined with fluoxetine 1

Efficacy Profile

Olanzapine demonstrates effectiveness in several aspects of bipolar disorder management:

• Superior to placebo in reducing manic symptoms and inducing remission 2
• May be more effective than lithium in preventing relapse into mania, but not depression 3, 4
• Effective for both acute treatment of manic episodes and long-term prevention of relapse 3
• When combined with fluoxetine, effective for bipolar depression 1

Place in Treatment Algorithm

For Acute Mania/Mixed Episodes:

1. Consider atypical antipsychotics as first-line treatment for bipolar I disorder
   • However, aripiprazole is preferred over olanzapine due to lower weight gain potential 5
2. Olanzapine can be used as:
   • Monotherapy for acute treatment
   • Adjunctive therapy with lithium or valproate when monotherapy is insufficient 1

For Maintenance Treatment:

1. Continue effective acute treatment for maintenance
2. Treatment should be continued for at least 2 years after the last episode 5
3. Olanzapine is effective at delaying or preventing relapse during long-term maintenance therapy in treatment responders 3

Safety and Tolerability Concerns

Olanzapine has significant safety considerations that limit its use as a first-line agent:

• Associated with substantial weight gain and metabolic side effects 5, 6
• Regular monitoring required for:
  • Weight and BMI
  • Fasting glucose
  • Lipid panel
  • Blood pressure 5
• Lower incidence of extrapyramidal symptoms compared to typical antipsychotics 3, 4

Special Populations

Adolescents (13-17 years):

• Efficacy established in one 3-week trial for manic/mixed episodes 1
• Increased potential for weight gain and dyslipidemia compared to adults
• Other drugs should be considered first due to long-term metabolic risks 1

Elderly:

• Black box warning for increased mortality in elderly patients with dementia-related psychosis 1
• Not approved for treatment of dementia-related psychosis

Combination Therapy Considerations

• Combination of olanzapine with lithium or valproate may be more effective than mood stabilizer monotherapy for acute mania 6
• When using combination therapy, the goal should be to use one antipsychotic at a time 5
• Olanzapine combined with fluoxetine is indicated for bipolar depression, while olanzapine monotherapy is not 1

Monitoring Recommendations

Patients on olanzapine require regular monitoring of:

• Mood symptoms and medication adherence
• Weight and metabolic parameters (glucose, lipids)
• Sexual function using validated scales
• Suicidal ideation
• Functional status 5

Practical Considerations

• Starting dose is typically 5-10 mg daily for adults with bipolar disorder
• Target dose of 10 mg/day is often effective
• Doses above 10 mg/day were not demonstrated to be more efficacious than 10 mg/day 1
• Lower starting doses (5 mg) recommended for debilitated patients, those with hypotensive risk, or slower metabolism 1

Olanzapine remains a valuable option for bipolar disorder treatment, but clinicians must carefully weigh its efficacy against metabolic risks, particularly when considering long-term maintenance therapy.