What are the side effects of Zyprexa (olanzapine)?

Olanzapine (Zyprexa) Side Effects

Olanzapine (Zyprexa) has significant metabolic side effects including weight gain, hyperglycemia, and dyslipidemia, with increased risk of developing type 2 diabetes, particularly in patients taking second-generation antipsychotics. 1, 2

Major Side Effects by Category

Metabolic Effects

• Weight gain: One of the most common and concerning side effects
  • More pronounced in adolescents and younger patients 2
  • More severe in patients with schizophrenia compared to those with bipolar disorder 3
  • Can be clinically significant (often 5-10kg or more with long-term use)
• Hyperglycemia and diabetes risk:
  • May lead to ketoacidosis, coma, or death in severe cases 2
  • Requires baseline and regular blood glucose monitoring
  • Patients should be screened for diabetes at baseline, 12-16 weeks after starting treatment, and annually thereafter 1
• Dyslipidemia:
  • Elevated triglycerides, total cholesterol, and VLDL cholesterol 4
  • More common in adolescents than adults 2

Neurological Effects

• Somnolence/sedation: Very common, especially during initial treatment 1, 2
• Dizziness: Particularly when changing positions (orthostatic hypotension) 1
• Extrapyramidal symptoms (EPS):
  • Less common than with typical antipsychotics but still occurs
  • Includes parkinsonism, akathisia, and tardive dyskinesia 1
  • Higher risk when combined with other dopamine antagonists 5

Other Common Side Effects

• Anticholinergic effects:
  • Dry mouth
  • Constipation
  • Blurred vision 6
• Increased appetite 2
• Drowsiness/fatigue 1
• Elevated liver enzymes (usually transient) 7

Serious Adverse Effects

Boxed Warnings

• Increased mortality in elderly patients with dementia-related psychosis:
  • Not approved for use in this population 2
  • Higher risk of death compared to placebo in this specific population

Other Serious Concerns

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS):
  • Rare but potentially fatal skin reaction
  • Symptoms include rash, fever, swollen lymph glands 1, 2
• Neuroleptic Malignant Syndrome:
  • Rare but potentially fatal
  • Symptoms include high fever, muscle rigidity, altered mental status 2

Special Population Considerations

Elderly Patients

• Higher sensitivity to side effects
• Recommended lower starting dose (2.5-5 mg) 1, 5
• Increased risk of falls, sedation, and orthostatic hypotension 5

Children and Adolescents

• Greater risk of weight gain, sedation, and metabolic effects 2
• Higher increases in prolactin, liver enzymes, and somnolence compared to adults 2

Patients with Hepatic/Renal Impairment

• Dose reduction recommended 5
• Closer monitoring of side effects needed

Monitoring Recommendations

1. Baseline assessment:

   • Weight, BMI
   • Fasting blood glucose
   • Lipid profile
   • Blood pressure
   • Liver function tests

2. Follow-up monitoring:

   • Weight: At each visit
   • Blood glucose: 12-16 weeks after initiation, then annually 1
   • Lipid profile: Periodically, especially in at-risk patients
   • Signs of tardive dyskinesia: Regular assessment

Risk Mitigation Strategies

• Consider lower starting doses (5 mg) in elderly or sensitive patients 1
• Monitor weight regularly and implement dietary/exercise interventions early
• Consider medication alternatives with lower metabolic risk (e.g., aripiprazole) for high-risk patients 4
• Avoid combining with other dopamine antagonists (metoclopramide, phenothiazines, haloperidol) 1, 5

Drug Interactions

• Potential for increased sedation when combined with CNS depressants or alcohol 2
• Caution with CYP1A2 inhibitors (e.g., fluvoxamine) which may increase olanzapine levels
• Risk of excessive sedation and respiratory depression when combined with benzodiazepines 1

Olanzapine's side effect profile requires careful consideration of risks versus benefits, particularly regarding metabolic complications that can significantly impact long-term morbidity and mortality. Regular monitoring and early intervention for side effects are essential components of treatment.