Can I increase the dose of olanzapine to 22.5mg?

Olanzapine Dosage Increase to 22.5mg

Increasing olanzapine dosage to 22.5mg is not recommended as it exceeds the FDA-approved maximum dose of 20mg daily, which could increase the risk of adverse effects without clear evidence of additional benefit for most patients.

Evidence-Based Rationale

The FDA-approved olanzapine label clearly indicates that the recommended maximum dose is 20mg daily 1. While there is some evidence that higher doses are being used in clinical practice, this practice exceeds regulatory approval and should be approached with caution.

Dosing Guidelines for Olanzapine

According to the evidence:

• Standard olanzapine dosing ranges from 2.5-20mg daily 1
• The ESMO Clinical Practice Guidelines recommend starting doses of 2.5-5mg for olanzapine with scheduled dosing of 2.5-5mg daily (usually at bedtime) 2
• Dose reductions are specifically recommended in:
  • Older patients
  • Patients with hepatic impairment
  • When combining with benzodiazepines (due to risk of oversedation and respiratory depression) 2

Safety Concerns with Higher Dosing

Exceeding the 20mg maximum dose may lead to:

• Increased risk of metabolic effects (weight gain, lipid abnormalities) 2, 3
• Higher risk of sedation and orthostatic hypotension 2
• Elevated prolactin levels at higher doses 3
• Greater anticholinergic burden (olanzapine has high central anticholinergic activity) 2

Clinical Evidence for Higher Doses

While some evidence suggests that doses above 20mg/day are being used in clinical practice 3, the supporting evidence for this practice is limited:

• A study noted that the average dose in New York State psychiatric centers increased from 17.4 to 22.5mg/day between 1997-2003 3
• Limited double-blind trials suggest higher doses may help selected treatment-resistant patients or those with high levels of psychopathology 3
• However, these potential benefits must be balanced against increased risks of adverse effects

Alternative Approaches

If the current olanzapine dose is not providing adequate symptom control, consider these evidence-based alternatives:

1. Optimize current dose within approved range:

   • Ensure the patient is receiving the maximum FDA-approved dose of 20mg before considering alternatives 1

2. Consider clozapine augmentation strategies if dealing with treatment-resistant symptoms:

   • Augmentation with amisulpride or aripiprazole may be beneficial for persistent positive symptoms 2
   • Electroconvulsive therapy can be considered for augmentation 2
   • Antidepressant augmentation may help with negative symptoms 2

3. For negative symptoms:

   • If positive symptoms are well-controlled, consider a gradual reduction of antipsychotic dose while remaining in therapeutic range 2
   • Consider switching to cariprazine or aripiprazole 2
   • Low-dose amisulpride (50mg twice daily) may be effective for predominant negative symptoms 2

Monitoring Recommendations

If despite these considerations, a clinical decision is made to exceed the 20mg dose:

• Implement more frequent monitoring of metabolic parameters
• Monitor BMI, waist circumference, and blood pressure weekly for 6 weeks 2
• Check fasting glucose 4 weeks after any dose increase 2
• Repeat all metabolic measures (BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function tests) after 3 months 2
• Consider adjunctive metformin when using higher doses of olanzapine to mitigate metabolic effects 2

Common Pitfalls to Avoid

• Assuming that higher doses will necessarily lead to better efficacy without considering the increased risk profile
• Failing to consider alternative antipsychotics or augmentation strategies before exceeding approved doses
• Not implementing more rigorous monitoring when using higher-than-approved doses
• Combining high-dose olanzapine with benzodiazepines, which can increase the risk of oversedation and respiratory depression 2

In conclusion, while olanzapine dosing above 20mg daily occurs in clinical practice, it exceeds regulatory approval and should only be considered after exhausting other evidence-based approaches, with careful monitoring for adverse effects.