ZYPREXA belongs to a class of medications called atypical antipsychotics. These medications are a newer class of antipsychotics that are indicated for the treatment of schizophrenia. They appear to have certain advantages over the traditional antipsychotics. In addition, because ZYPREXA is approved for the treatment of bipolar mania (a mood disorder), it is categorized as a psychotropic. Although it is not entirely clear how antipsychotics or psychotropics work in the body, it is believed that ZYPREXA works by adjusting the imbalance of chemicals in the brain that may cause your symptoms. By doing so, ZYPREXA may help restore more normal thinking and mood, and can help you manage your symptoms as you continue your treatment.

Additional information from PsychEducation.org: Technically this is an antipsychotic as well as a "mood stabilizer". (What's an antipsychotic?) But within weeks of its release by the FDA as an antipsychotic, psychiatrists were figuring out that it had acute mood stabilizing properties. Since then the manufacturer has obtained FDA approval for marketing olanzapine as a mood stabilizer. This means that a doctor could offer you an "antipsychotic" when you don't have "psychosis" at all. Instead, she could be offering it to you simply because it's a very fast, often extremely effective medication for the symptoms of bipolar disorder (it even may help antidepressants work in people who don't clearly have bipolar disorder).

This medication can be unbelievably effective, with remarkably few side effects. But brace yourself, and don't stop reading until the end of this little essay because there may be some good news in sight. However, you need to know that in routine doses (10-20mg) it can cause a lot of weight gain. There is a case report of a 58% body mass increase, and a recent thorough review ranked olanzapine just behind clozapine in the weight gain championships, at 10 lbs in 10 weeks! Twenty-five pounds in a year is not uncommon. Thus the big risk from this medication, the main limiting factor (beside it's phenomenal cost) to it's use in bipolar disorder, is this risk of weight gain.

In addition, there is accumulating evidence that this medication can cause diabetes in some people, usually -- but not always -- because of the weight gain it can cause. The FDA requested that Eli Lilly put a warning about this on their package insert.^FDA A 2004 Consensus Statement from the American Diabetes Association, along with the American Psychiatric Association, includes specific warnings about diabetes and even a severe diabetic complication called "DKA" (for more detail on the Consensus Statement as I've reviewed it for doctors, who must present "PAR -- Procedures/Alternatives/Risks" information to patients, see Zyprexa Risks in PAR Discussions).

Nevertheless, you should be aware of Zyprexa for symptoms that simply must be controlled now. It can decrease anxiety, agitation, even the overall negative feeling called "dysphoria" -- within 20 to 30 minutes. It has a profoundly calming effect in many people. It can stop "racing thoughts" that can be one of the most severe symptoms of bipolar disorder, especially in Bipolar II -- as well as the more obvious symptoms of paranoia or delusions as seen in Bipolar I. Sometimes tiny doses are enough to help a lot, and these doses do not seem to so commonly lead to weight gain (2.5mg is the smallest pill; sometimes even half of that is quite useful in bipolar II).

Because it can treat both mood symptoms and psychotic symptoms, it has a role also in people where the diagnosis is not clear. The doctor does not have to be certain whether you have bipolar disorder or schizophrenia or even "depression with psychotic features": all will respond. It is like a "broad-spectrum antibiotic" that doctors can use before they are certain just which bacteria you have. Later more specific medications can be used.

Why switch , if Zyprexa works well right away? Fair question. The risk of weight gain and possibly even getting diabetes is the main reason to consider switching (if you're paying for the medication yourself, that's the other reason -- it's so expensive, you may not want to buy more than a few pills). The risk of weight gain is higher if you're thin; people who are already overweight are less likely to see big gains from Zyprexa.

Finally, you should know that research is continuing on the use of medications to block this weight gain, or even reverse it. There are five main strategies being evaluated:

H2 blockers
Somehow these medications appear to decrease the appetite drive caused by Zyprexa. However, the only formal study of this approach concluded that the early apparent benefit seemed to be lost by 4 months. Even when it was working, it was not causing weight loss, just less gain.

Amantidine
The olanzapine manufacturer seems to like this idea much more than metformin (below). My guess is that metformin treats a problem they don't want to admit Zyprexa sometimes causes -- diabetes. So far amantadine has only one small study without a placebo group. Note that there is weight loss reported here, and it was still there at 6 months.

Topiramate
This is not my favorite drug, in part because people get so excited about it when they hear "weight loss" that they stop evaluating the risks very well. However, it clearly blocks appetite and clearly leads to weight loss in many people who take it. But there are now two formal research studies with placebo groups ( reference -- P. Keck: 5th International Bipolar conference) which show this medication does not act like a mood stabilizer, so there is no additional benefit to be generally expected (although there appear to be some people, in my practice at least, who have done extremely well on it -- I just don't know how to predict who's who!). There is a least one case report of topiramate inducing mania. Here's more on Topomax, including information on risks.

Metformin
Just as with amantadine, there is only one small study with no placebo group.. Read more general information about metformin (Glucophage) if you wish. Basically this medication appears to be able to reverse a change in your body to which Zyprexa can lead, called "metabolic syndrome". This ability led to the medication being studied as an "antidote" of sorts for Zyprexa-induced weight gain.

On the basis of the limited information we have so far; and because there is just a glimmer of evidence that metformin might be able to treat mood symptoms all by itself (see above links); this is in my opinion worth considering to prevent weight gain in people who cannot avoid weight gain through diet and exercise approaches while taking Zyprexa.

If you are taking Zyprexa or thinking of taking Zyprexa and you are wondering about side effects or the potential of side effects with using Zyprexa, there is something you need to know. There is a way to predict adverse reactions with a very simple test.

Dr. Lester M. Crawford, Acting FDA Commissioner had this to say about this test on
Dec. 24, 2004. “Physicians can use the genetic information from this test to prevent harmful drug interactions and to assure drugs are used optimally, which in some cases will enable patients to avoid less effective or potentially harmful treatment choices,”

Advanced DNA Testing offers this test to the public and physicians. Click here to go directly to the Advanced DNA Testing Web Site or call them at 1-888-697-8938.

Zyprexa and it's effectiveness for longer-term use, that is, for more than 4 weeks treatment of an acute episode, and for prophylactic use in mania, has not been systematically evaluated in controlled clinical trials.

Neuroleptic Malignant Syndrome (NMS) - A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including Zyprexa. Manifestations of (NMS) are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia), and acute renal failure.

Tardive Dyskinesia - A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with Zyprexa. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of Zyprexa increases.

Orthostatic Hypotension (Lowered blood pressure when a person changes from a setting to an erect position) - Zyprexa may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period. Zyprexa should be used with particular caution in patients with known cardiovascular disease, cerebrovascular disease, and conditions which would predispose patients to hypotension.

Seizures - Seizures during premarketing test showed 22 of 2500 people developed seizures.

Potential for Cognitive and Motor Impairment - Sleepiness, unnatural drowsiness, was a commonly reported adverse event associated with Zyprexa treatment, occurring at an incidence of 26%. Since Zyprexa has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles.

"Researchers and clinical psychopharmacologists do not fully know what causes schizophrenia. Side effects of Zyprexa include slowing of voluntary movement, expressionless face, rigidity and tremor of arms and head, abnormal toxicity of muscle tissues, and restlessness."

Zyprexa Can Cause Diabetes -
Eli Lilly is now trying to get the FDA to approve diabetes medication

Could this be the scam of the century? Bring out Prozac, which has a diabetes side effect, then Zyprexa with the same side effect, they get approved a medication to treat the disease you created for millions?

New Drug Application for Exenatide Submitted to FDA for Type 2 Diabetes

June 30, 2004

Amylin Pharmaceuticals, Inc., (Nasdaq: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for regulatory approval of exenatide. Exenatide is the first in a new class of medicines known as incretin mimetics under investigation for the treatment of type 2 diabetes. In clinical trials, exenatide has demonstrated reductions in blood sugar and improvements in markers of beta cell function. Patients in exenatide studies also lost weight.

"The submission of the exenatide NDA is a significant milestone both for Amylin Pharmaceuticals and for our collaboration with Eli Lilly and Company," said Ginger Graham, president and CEO, Amylin Pharmaceuticals. "This NDA includes data on more than 1,800 subjects treated with exenatide. We believe the application provides the FDA with the necessary information to evaluate exenatide for use as a new therapeutic option for people living with type 2 diabetes."

"The rapid increase in the prevalence of diabetes and the need for innovative new treatments has never been more critical than it is today," said John C. Lechleiter, Ph.D., executive vice president of pharmaceutical operations, Eli Lilly and Company. "Many patients with type 2 diabetes are struggling to control their blood sugar and, even with current oral therapies, find that they cannot reach their treatment goals. If approved, we believe exenatide could offer an important and novel treatment option for people with type 2 diabetes."

The exenatide NDA is made up of three major components; chemistry and manufacturing, preclinical and clinical. The clinical component of the submission is based largely on 30-week data from three blinded pivotal trials of exenatide involving more than 1,400 patients who were unable to control their blood sugar on common oral therapies including metformin, sulfonylurea or a combination of both. The submission also includes 52-week open-label data from the extensions of these pivotal studies and from an additional open-label study. In the pivotal studies, exenatide demonstrated statistically significant, sustained reductions in average blood sugar levels as measured by hemoglobin A1c (A1C). Patients in these studies also demonstrated progressive reductions in weight, a secondary endpoint of the studies. The open-label studies demonstrated that the reductions in A1C were sustained through 52 weeks of treatment with average reductions of approximately 1.1 percent. Reductions in weight were also sustained through 52 weeks of treatment with average reductions of approximately eight pounds. In addition, the exenatide data showed improvements in beta cell function, as measured by HOMA-B and proinsulin to insulin ratios, and the restoration of first-phase insulin response, a fundamental response lost early in the development of type 2 diabetes. Exenatide was generally well tolerated across the pivotal trials. The most common adverse event reported was mild to moderate nausea, which occurred primarily at initiation of therapy.

Exenatide is formulated as a sterile, injectable product that, if approved, will be delivered by a pen delivery system.

About Diabetes

Diabetes affects an estimated 194 million adults worldwide¹ and more than 18 million in the United States.² Approximately 90-95 percent of those affected have type 2 diabetes, a disease in which the body does not produce enough insulin and the cells in the body do not respond normally to the insulin. According to the U.S. Center for Disease Control and Prevention’s National Health and Nutrition Examination Survey, approximately 60 percent of diabetes patients do not achieve target A1C levels with their current treatment regimen. According to the American Diabetes Association, patients with A1Cs above target are more likely to develop diabetes-related complications, such as kidney disease, blindness and heart disease.³

Risperdal (Prescription)
Prescription Drugs from Norphar.com are priced in U.S. Dollars.

Drug Name and Quantity per Container	Generic Name	Price for 100 tabs
ZYPREXA TB 2.5MG	olanzapine	$178.42
ZYPREXA TB 5MG	olanzapine	$341.80
ZYPREXA TB 7.5MG	olanzapine	$515.31
ZYPREXA TB 10MG	olanzapine	$653.92

Drug Name and Quantity per Container	Generic Name	Quantity	Price
RISPERDAL TB 0.25MG BLSPK	Risperidone	100 tabs	$67.69
RISPERDAL TB 0.5MG BLSPK	Risperidone	100 tabs	$76.75
RISPERDAL TB 1MG BLSPK	Risperidone	180 tabs	$229.18
RISPERDAL TB 2MG BLSPK	Risperidone	180 tabs	$440.97
RISPERDAL TB 3MG BLSPK	Risperidone	180 tabs	$653.09