Olanzapine is being positioned as a foundational mood stabilizer (i.e. the basic treatment to which all others are added) that is more effective and easier to use than lithium. Broad-spectrum efficacy is emphasized by Lilly in their key communications, e.g. “Zyprexa is the first treatment in nearly 30 years to be recognized by the FDA as a treatment for both acute mania and maintenance treatment in bipolar disorder” (Lilly Press Release, January 2004). Additionally, olanzapine and fluoxetine in combination (OFC, Symbyax) is positioned to fill the need for the acute treatment of bipolar depression.

The main weakness of olanzapine is its propensity to cause weight gain, which has been consistently demonstrated in every clinical trial. Additionally, recent US label changes for the atypicals as a class include warnings for diabetes and hyperglycemia. These adverse events clearly are of particular significance in long-term maintenance treatment.

These recent label changes have raised questions about the general tolerability of the atypical antipsychotics as a class, which have always claimed improved tolerability versus the conventional antipsychotics (e.g. haloperidol). The class warnings are of interest as Lilly has, for example, (unofficially) positioned its competitor risperidone as “the least atypical of the atypicals”, claiming that olanzapine has a superior tolerability profile.

Strengths:

1. Well-documented efficacy in acute mania and maintenance therapy – less so for bipolar depression (OFC). 
2. Potential antidepressant effect.
3. Low EPS risk (compared with conventional antipsychotics, e.g. haloperidol).

Weaknesses:

1. Causes weight gain.
2. Associated with diabetes and hyperglycemia (class effect).
3. Associated with hyperprolactemia (class effect). 
4. Associated with somnolence and depression (side effect).