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Bipolar Disorder Medication Spotlight: Zyprexa (Olanzapine)

With this post, we continue our biweekly series on medications used to treat bipolar disorder and related symptoms. This week, we shift our focus from anti-seizure medications to atypical antipsychotics – also known as second-generation antipsychotics or atypical neuroleptics.

Atypical antipsychotics were designed primarily to treat schizophrenia but have proven effective in treating mania and mixed-manic episodes and in the maintenance treatment of bipolar disorder. They are generally very useful in treating psychotic “breaks” that may accompany severe manic episodes. The atypicals may also be helpful in treating depression. This post shines the light on Zyprexa (olanzapine) – the first atypical antipsychotic approved for the treatment of acute bipolar mania.

These medications are called “atypical” because they work a little differently than the older, standard antipsychotics, including Thorazine and Haldol. The older generation of medications carried risks of movement and muscle disorders that could be irreversible. The “second generation” group does not carry as high a risk of movement problems but carries its own set of risks that can be as difficult to manage. Several large recent studies have clearly indicated that the older medications are often equally effective to the newer ones and that the side-effect profiles, while different, are no better or worse in terms of patient satisfaction. In particular, the older medications do not typically cause weight gain, which is one of the biggest problems with the newer ones.

All antipsychotic medications work by blocking the neurotransmitter dopamine. The different medications do this to lesser or greater degrees and they also have differing effects on other transmitter systems, most notably serotonin. This group of medications is powerful and typically quite effective at eliminating psychosis (hallucinations and delusions, for example) and at reducing overall agitation and manic excitement. Some of the atypicals have an antidepressant effect as well, which can make them valuable in bipolar disorder.

People who don’t respond well to the first-tier bipolar medications, including lithium and Depakote, often respond well to one of the atypical antipsychotics – either alone or in tandem with other bipolar medications.

The side effects that can be seen with these medications include the following:

  • Weight gain is the most prominent and unpleasant side effect of most of these medications.
  • Increased risk of developing metabolic syndrome (pre-diabetes) and diabetes and problems with sugar metabolism.
  • Increased cholesterol and other changes in fat and lipid metabolism.
  • Movement problems like Parkinson’s disease (tremors and stiffness) (lower risk than older medications).
  • Irreversible uncontrolled movements called tardive dyskinesia – facial twitches or uncontrolled movements of the tongue, lips, arms, or other body parts (lower risk than older medications).
  • Akathisia – a feeling of extreme restlessness commonly described as the overwhelming desire to “jump out of your skin.”
  • Changes in cardiac rhythms.
  • Increases in the levels of the hormone prolactin – sometimes causing breast enlargement in men and lactation or menstrual problems in women.

The weight gain issue is the biggie for most people, especially in the case of Zyprexa. Some patients report gaining over 50 pounds in a matter of weeks, which can lead to other serious medical conditions, including diabetes. Of course, the weight gain also creates a host of other problems related to general well being and self image. Although diet and exercise may alleviate the weight gain for some people, these solutions are often unrealistic and place a further burden someone who’s already dealing with plenty of emotional pain and stigma. (See “Preventing and Reversing Weight Gain Associated with Psychiatric Medications.”)

Lilly offers Zyprexa in four formulations:

  • Zyprexa IntraMuscular (for injection), which is used to treat extreme agitation – overexcited, hostile, or threatening behavior – in people with schizophrenia or bipolar disorder. This is usually used to treat acute mania and/or psychosis. Later, your doctor is likely to switch you to a different form of Zyprexa or a different medication altogether for long-term maintenance.
  • Zyprexa oral – the most common type prescribed.
  • Zydis – a melt in your mouth wafer version of Zyprexa.
  • Symbyax – a combination of Prozac (fluoxetine) and Zyprexa (olanzapine), designed to treat both depression and mania.

If you’ve taken any form of Zyprexa for bipolar disorder or are a doctor who has prescribed it, please share your experiences, insights, and observations.

Bipolar Disorder Medication Spotlight: Zyprexa (Olanzapine)

Candida Fink, MD

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APA Reference
Fink, C. (2008). Bipolar Disorder Medication Spotlight: Zyprexa (Olanzapine). Psych Central. Retrieved on July 15, 2020, from


Last updated: 7 Nov 2008
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