What is the recommended approach for using Zyprexa (olanzapine) to treat anxiety in a patient with bipolar disorder?

Olanzapine (Zyprexa) for Anxiety in Bipolar Disorder

Primary Recommendation

Olanzapine is highly effective for treating anxiety symptoms in patients with bipolar disorder, particularly when anxiety occurs during mood episodes or as a comorbid anxiety disorder, and should be initiated at 5-10 mg/day as adjunctive therapy to a mood stabilizer like lithium or valproate. 1, 2

Evidence-Based Treatment Algorithm

First-Line Approach: Mood Stabilization with Olanzapine Augmentation

When anxiety is present during a mood episode:

• Prioritize treating the underlying mood disturbance first, as anxiety symptoms typically improve with mood stabilization 1, 3
• Start olanzapine 10-15 mg/day for acute mania with anxiety, or 5-10 mg/day when adding to existing mood stabilizer therapy 4, 2
• Olanzapine demonstrates superior efficacy compared to lamotrigine for anxiety reduction when added to lithium in patients with comorbid anxiety disorders 2

For established bipolar disorder with comorbid anxiety disorder:

• Add olanzapine 5-10 mg/day to existing lithium or valproate therapy 1, 2
• In a randomized trial, olanzapine addition to lithium produced significant HAM-A score reductions (p < .001) and was more effective than lamotrigine at weeks 6 and 12 2
• Mean effective dose is 7.7 mg/day when used as adjunctive therapy 2

Alternative Atypical Antipsychotics with Anxiolytic Properties

If olanzapine is contraindicated due to metabolic concerns:

• Quetiapine has demonstrated anxiolytic properties and efficacy in bipolar disorder with anxiety 1, 3
• Risperidone shows efficacy in specific anxiety disorders (PTSD, OCD) but did not separate from placebo as monotherapy for anxiety in bipolar disorder 5, 3
• Aripiprazole offers a more favorable metabolic profile but has less robust evidence for anxiety specifically 6

Mood Stabilizer Selection for Anxious Bipolar Patients

Valproate (divalproex) is the preferred mood stabilizer when anxiety is prominent:

• Initial dosage: 125 mg twice daily, titrated to therapeutic blood level of 40-90 mcg/mL 1
• Valproate has demonstrated efficacy in panic disorder in placebo-controlled trials 5
• Studies suggest valproate may be the mood stabilizer of choice for anxious bipolar patients 3

Lamotrigine as an alternative:

• Effective for anxiety reduction when added to lithium (50-200 mg/day, mean 96.7 mg/day) 2
• Particularly useful for bipolar depression with anxiety 6
• Slower onset than olanzapine but better tolerated metabolically 2

Critical Monitoring Requirements

Baseline metabolic assessment before starting olanzapine:

• Body mass index, waist circumference, blood pressure 6
• Fasting glucose and fasting lipid panel 6
• Olanzapine carries one of the highest risks for weight gain among atypical antipsychotics 1

Follow-up monitoring schedule:

• BMI monthly for 3 months, then quarterly 6
• Blood pressure, fasting glucose, and lipids at 3 months, then yearly 6

Medications to Avoid or Use Cautiously

Benzodiazepines should be limited:

• Regular benzodiazepine use leads to tolerance, addiction, depression, and cognitive impairment 1
• Approximately 10% of patients experience paradoxical agitation 1
• If necessary, use infrequent, low doses with short half-lives (e.g., lorazepam 0.25-0.5 mg PRN, maximum 2 mg daily) 1

Antidepressant monotherapy is contraindicated:

• Risk of mood destabilization, mania induction, and rapid cycling 1, 6
• If antidepressants are needed for comorbid anxiety, always combine with mood stabilizers 1

Adjunctive Non-Pharmacological Interventions

Cognitive-behavioral therapy should be routinely offered:

• Strong evidence for both anxiety and depression components in bipolar disorder 1
• Increases treatment adherence and improves long-term outcomes 1

Psychoeducation is essential:

• Provide information about symptoms, treatment options, and medication adherence 1, 6
• Family-focused therapy enhances problem-solving and communication skills 1

Common Pitfalls to Avoid

Do not treat anxiety in isolation without addressing mood stability:

• Anxiety occurring during mood episodes improves with mood stabilization 3
• Attempting to treat anxiety before achieving mood stability risks treatment failure 1

Avoid premature discontinuation:

• Maintenance therapy should continue for at least 12-24 months after stabilization 6
• Withdrawal of maintenance therapy dramatically increases relapse risk 6

Do not use typical antipsychotics:

• Haloperidol and other typical antipsychotics carry 50% risk of tardive dyskinesia after 2 years in young patients 7
• Atypical antipsychotics are superior for tolerability and efficacy 7, 5

Duration of Treatment

Acute phase (anxiety during mood episode):

• Continue olanzapine until mood episode resolves and anxiety symptoms improve (typically 3-4 weeks) 4

Maintenance phase (comorbid anxiety disorder):

• Continue combination therapy for minimum 12-24 months 6
• Some patients require lifelong treatment when benefits outweigh metabolic risks 1, 6