Table of Contents

Volume 2, Issue 3                                                                                            March, 2016

Olanzapine structure

Drug of the Month:
Olanzapine (Zyprexa)

Some benefit, many harms

Biological mechanism

Olanzapine is a dopamine blocker with potent D2 receptor blockade, along with strong anticholinergic effects.  The D2 blockade is dose dependent, such that at 10-20 mg/d, over 90% of D2 receptors are blocked.  This level of D2 blockade produces extrapyramidal symptoms (EPS) such as parkinsonian tremor and ridigity, and akathisia.  The parkinsonian effects are somewhat mitigated by this agent’s anticholinergic properties, but the latter cause their own side effects, especially cognitive impairment, sedation, and constipation.  

Like all modern dopamine blockers, it also has serotonin-2 receptor blockade, which likely produces weight gain.  

Olanzapine also has strong anti-insulin effects, which produces the dire metabolic syndrome of diabetes, hypertension, and hyperlipidemia, along with marked weight gain and abdominal girth. 

Other features

Olanzapine causes notable abnormalities in liver function tests (LFTs), more so than divalproex, and it can cause death by acute diabetic ketoacidosis.

Clinical efficacy

Olanzapine has been shown to be effective for manic episodes and for schizophrenia, and also has  FDA indication for maintenance treatment of bipolar illness.  It has been proven ineffective in the acute major depressive episode in both bipolar depression and in MDD.  However, when combined with fluoxetine (olanzapine-fluoxetine combination, Symbyax), it has been proven effective for the acute bipolar depressive episode.  

In the CATIE study, it was shown to be very effective for schizophrenia, but it also had more side effects and was less safe than other antipsychotics. 

Fast facts: Olanzapine (Zyprexa®) 

Typical dose:  5-20 mg/d (range )

Biological mechanism: dopamine and serotonin receptor blockade, anti-insulin effects

Typical side effects: marked weight gain, EPS, sedation, constipation

Less common but important side effects: metabolic syndrome

Medically important side effects:  metabolic syndrome

Clinically proven efficacy: Acute mania, schizophrenia


5-10 mg/d are effective for moderate mood states, with higher doses need for severe mania and schizophrenia. 

The PL Bottom Line

  • Olanzapine is very effective for acute mania and schizophrenia.  
  • It is much less safe than most other dopamine blockers.  
  • Its other utility, such as in maintenance treatment in bipolar illness, is questionable for the reasons given in the Special Article.

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