Does Zyprexa (Olanzapine) Cause Insomnia?
No, Zyprexa (olanzapine) does not typically cause insomnia—in fact, insomnia is listed as a common adverse effect in only 12% of patients taking olanzapine compared to 11% on placebo, and the medication is more commonly associated with somnolence (sedation) as a side effect. 1
Evidence from FDA Drug Labeling
The FDA-approved prescribing information for olanzapine provides clear data on sleep-related adverse effects:
- Insomnia occurred in 12% of olanzapine-treated patients versus 11% on placebo in short-term controlled trials for schizophrenia, showing essentially no difference 1
- Somnolence (sleepiness) was far more common, occurring in 29% of olanzapine patients versus only 13% on placebo 1
- The most frequently observed adverse reactions with olanzapine include somnolence, weight gain, dizziness, and dry mouth—not insomnia 1
Clinical Context: Olanzapine's Sedating Properties
Olanzapine is actually recognized for its sedating effects rather than causing insomnia:
- Research demonstrates that olanzapine improves sleep continuity and reduces latency to slow-wave sleep in patients with depression 2
- A small open trial found olanzapine (2.5-10 mg) provided positive results in 8 of 9 patients with chronic insomnia from various sleep disorders 3
- Comparative studies show that olanzapine causes significantly less insomnia than other antipsychotics—in meta-analyses, olanzapine was associated with increased odds of insomnia compared to clozapine, but this reflects clozapine's exceptional sedating properties rather than olanzapine being activating 4
Important Clinical Guideline Perspective
Major sleep medicine guidelines explicitly warn against using olanzapine for primary insomnia treatment 5:
- The American Academy of Sleep Medicine states that atypical antipsychotics like olanzapine should not be used off-label for chronic primary insomnia due to weak supporting evidence and potential for significant adverse effects including weight gain, metabolic syndrome, and neurological side effects 5
- A systematic review found very low quality evidence for atypical antipsychotics in insomnia treatment, with these medications reserved only for patients with comorbid psychiatric conditions requiring their primary mechanism of action 6, 5
Common Pitfalls and Caveats
If a patient on olanzapine reports insomnia, consider these alternative explanations:
- Underlying psychiatric condition: The insomnia may be a symptom of the primary disorder (schizophrenia, bipolar disorder, depression) rather than a medication side effect 1
- Paradoxical activation: While rare, some patients may experience restlessness or akathisia (reported in 3-5% of patients) which can be mistaken for insomnia 1
- Dose-related effects: Higher doses may paradoxically cause more agitation in some individuals 1
- Concurrent medications: SSRIs, stimulants, decongestants, and other activating medications commonly co-prescribed with olanzapine are far more likely culprits for insomnia 7
Bottom Line
Olanzapine is a sedating medication that causes somnolence in approximately 1 in 3 patients, while insomnia occurs at essentially the same rate as placebo (12% vs 11%). If insomnia develops in a patient taking olanzapine, investigate other causes including the underlying psychiatric condition, concurrent medications, or behavioral factors rather than attributing it to the olanzapine itself. 1, 2