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Olanzapine
Systematic (IUPAC) name
2-methyl-4-(4-methyl-1-piperazinyl)-
10H-thieno[2,3-b][1,5]benzodiazepine
Identifiers
CAS number 132539-06-1
ATC code N05AH03
PubChem 4585
DrugBank APRD00138
Chemical data
Formula C17H20N4S 
Mol. mass 312. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Sulfur or sulphur (ˈsʌlfɚ see spelling below) is the Chemical element that has the Atomic number 16 The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 439
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability  ?
Metabolism Hepatic
Half life 21–54 hours
Excretion  ?
Therapeutic considerations
Pregnancy cat.

C
Legal status

Prescription only
Routes oral, intramuscular

Olanzapine (Zyprexa, Zyprexa Zydis, Zalasta, Zolafren, Olzapin, or in combination with fluoxetine Symbyax) is an atypical antipsychotic, approved by the FDA for the treatment of: schizophrenia on 1996-09-30 [1]; depressive episodes associated with bipolar disorder, as part of the Symbyax formulation, on 2003-12-24[2]; acute manic episodes and maintenance treatment in bipolar disorder on 2004-01-14[3]. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction In Pharmacology and Toxicology, a route The atypical antipsychotics (also known as second generation antipsychotics) are a group of Antipsychotic drugs used to treat psychiatric conditions Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn Year 1996 ( MCMXCVI) was a Leap year starting on Monday (link will display full 1996 Gregorian calendar) Events 1399 - Henry IV is proclaimed King of England. 1744 - France and Spain defeat the Year 2003 ( MMIII) was a Common year starting on Wednesday of the Gregorian calendar. Events 563 - The Byzantine church Hagia Sophia in Constantinople is dedicated for the second time after being destroyed by Earthquakes "MMIV" redirects here For the Modest Mouse album see " Baron von Bullshit Rides Again " Events 1129 - Formal approval of the Order of the Templar at the Council of Troyes. Off-label uses are listed below. Off-label use is the practice of prescribing drugs for a purpose outside the scope of the drug's approved label most often concerning the drug's indication.

The olanzapine formulations are manufactured and marketed by the pharmaceutical company Eli Lilly and Company, whose patent for olanzapine proper expires in 2011. Eli Lilly and Company ( is a global Pharmaceutical company and one of the world's largest corporations 2011 ( MMXI) will be a Common year starting on Saturday of the Gregorian calendar.

Contents

Pharmacology

Olanzapine is structurally similar to clozapine, and is classified as a thienobenzodiazepine. Clozapine (sold as Clozaril, Leponex, Fazaclo, Froidir; Gen-Clozapine in Canada Clozaril, Denzapine, A thienobenzodiazepine is a Heterocyclic compound containing a Diazepine ring fused to a Thiophene ring and a Benzene ring Olanzapine has a higher affinity for 5-HT2 serotonin receptors than D2 dopamine receptors. In the field of Neurochemistry, 5-HT receptors are receptors for the Neurotransmitter and peripheral signal mediator Serotonin, also Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the Vertebrate Central nervous system (CNS

Like most atypical antipsychotics, compared to the older typical ones, olanzapine has a lower affinity for histamine, cholinergic muscarinic and alpha adrenergic receptors. The histamine receptors are a class of G-protein coupled receptors with Histamine as their Endogenous Ligand. Muscarinic receptors, or mAChRs, are Acetylcholine receptors that form Metabotropic Ion channels in the Plasma membranes of certain The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the Catecholamines Adrenergic receptors The mode of action of olanzapine's antipsychotic activity is unknown. It may involve antagonism at serotonin receptors. Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons Antagonism of dopamine receptors is associated with extrapyramidal effects such as tardive dyskinesia, and with therapeutic effects. In Human anatomy, the extrapyramidal system is a Neural network located in the brain that is part of the Motor system involved in the coordination Tardive dyskinesia is a variety of dyskinesia (involuntary repetitive movements manifesting as a side effect of long-term or high-dose use of Dopamine antagonists Antagonizing H1 histamine receptors causes sedation and may cause weight gain, although antagonistic actions at 5-HT2C receptors have also been implicated in weight gain.

Dosing and administration

Olanzapine is available as a tablet in strengths of 2. 5 mg, 5 mg, 7. 5 mg, 10 mg, 15 mg and 20 mg and orally disintegrating wafers (known as Zydis), which dissolve on the tongue, in strengths of 5 mg, 10 mg, 15 mg and 20 mg. It is also available as a rapid-acting intramuscular injection for short-term acute use. Intramuscular injection is the injection of a substance directly into a Muscle.

Dose may be adjusted depending on the person's response to the drug. The dose also will depend on certain medical problems the person may have. It is generally recommended to be taken once daily before bed as it is highly sedating. A sedative, or more specifically a sedative-hypnotic, is a substance that depresses the Central nervous system (CNS resulting in calmness relaxation sleepiness

Pharmacokinetics

Olanzapine displays linear kinetics. Its elimination half-life ranges from 21 to 54 hours. Steady state plasma concentrations are achieved in about a week. Olanzapine undergoes extensive first pass metabolism and bioavailability is not affected by food. The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of Drug metabolism whereby the Concentration In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of

In cases of acute agitiation, olanzapine can also be administered by intramuscular injection in doses up to 10 milligrams. Olanzapine injection should not be given by the intravenous route, and should not be co-administered with benzodiazepines. The benzodiazepines (pronounced, often abbreviated to "benzos") are a class of Psychoactive drugs with varying Hypnotic

Metabolism

Olanzapine is metabolized by the cytochrome P450 system isoenzymes 1A2 and 2D6 (minor pathway). Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains Drug metabolism may be increased or decreased by agents that induce (e. g. cigarette smoke) or inhibit (e. g. fluvoxamine or ciprofloxacin) CYP1A2 activity respectively. Fluvoxamine ( Luvox) is an Antidepressant which functions as a Selective serotonin reuptake inhibitor.

Side effects

As with all neuroleptic drugs, olanzapine can cause tardive dyskinesia and rare, but life-threatening, neuroleptic malignant syndrome. Tardive dyskinesia is a variety of dyskinesia (involuntary repetitive movements manifesting as a side effect of long-term or high-dose use of Dopamine antagonists Neuroleptic malignant syndrome (NMS is a life-threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs.

Other recognised side effects may include:

Weight gain

Of the atypical antipsychotics, olanzapine and clozapine are the most likely to induce weight gain. Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of "inner" restlessness that manifests itself with an inability to sit still or remain Many different terms are often used to describe what is collectively known as dizziness. Sedation is a Medical procedure involving the administration of Sedative drugs generally to facilitate a medical procedure with Local anaesthesia. Insomnia is a symptom of a sleeping disorder characterized by persistent difficulty falling asleep or staying asleep despite the opportunity Orthostatic hypotension (also known as postural hypotension, and colloquially as head rush or a dizzy spell) is a form of Hypotension in which An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting Clozapine (sold as Clozaril, Leponex, Fazaclo, Froidir; Gen-Clozapine in Canada Clozaril, Denzapine, [4] The effect is more pronounced if high doses of olanzapine are used. [5] Smaller amounts of weight gain are induced by risperidone and quetiapine. Risperidone (pronounced Ris-PER-ǐ-dōn and sold under the trade name Risperdal in the Netherlands, United States, Canada, the Quetiapine ( kwe-TYE-a-peen marketed by AstraZeneca as Seroquel and by Orion Pharma as Ketipinor, is an Atypical antipsychotic Ziprasidone and aripiprazole are considered to be weight neutral antipsychotics. Ziprasidone (marketed as Geodon, Zeldox) was the fifth Atypical antipsychotic to gain FDA approval (February 2001 Aripiprazole (ay-ree-PIP-ray-zole (sold as Abilify) was approved by the Food and Drug Administration (FDA on November 15, 2002 for the

Recently the Food and Drug Administration required the manufacturers of all atypical antipsychotics to include a warning about the risk of hyperglycemia and diabetes with these drugs. Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of Glucose circulates in the Blood plasma Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc These effects may be related to the drugs' ability to induce weight gain, although there are some reports of metabolic changes in the absence of weight gain, and recent (2007) evidence suggests that olanzapine may directly affect adipocyte function, promoting fat deposition. Adipocytes are the cells that primarily compose Adipose tissue, specialized in storing energy as Fat. There are some case reports of olanzapine-induced diabetic ketoacidosis. Diabetic ketoacidosis (DKA is a life-threatening complication in patients with diabetes mellitus [6] There are data that suggest that olanzapine can decrease insulin sensitivity. [7], though there are other studies that seem to refute this[8]

Triglyceride levels rose from 99 to 166 in one year with olanzapine, in the CAFE ("Comparison of Atypicals for First-Episode Psychosis") study. (more properly known as, TAG or triacylglyceride) is Glyceride in which the Glycerol is Esterified with three Fatty acids It is the Of the three drugs administered in that study, "olanzapine was associated with the greatest increases in body weight and related measures. "[9] In the same study, where the median patient age was 23, 46% of male patients on Zyprexa had a waist size of 40" or greater after one year, and "80% gained 7% or more over their baseline weight compared with 57. 6% of those receiving risperidone and 50% of those receiving quetiapine. "[10] Impaired glucose metabolism, high triglycerides, and obesity have been shown to be constituents of the metabolic syndrome and may increase the risk of cardiovascular disease. Metabolic syndrome is a combination of medical disorders that increase the risk of developing Cardiovascular disease and diabetes. Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and

The results of a large, random-design study funded by NIH's National Institute of Mental Health were published in September 2005. "NIH" redirects here For other meanings of NIH see NIH (disambiguation. The National Institute of Mental Health ( NIMH) is part of the federal government of the United States and the largest research organization in the world specializing in The 18-month study, which involved 1,400 participants at 57 sites around the country, found that "patients on olanzapine also experienced substantially more weight gain and metabolic changes associated with an increased risk of diabetes than those participants taking the other drugs. "[11] However, the study also found that olanzapine helped more patients control symptoms for significantly longer than the other drugs. Specifically, after 18 months, the researchers found, "64 percent of the patients taking olanzapine had stopped, while at least 74 percent had quit each of the other medications. "[12]

Data from a small, open-label, non-randomized study seem to suggest that taking olanzapine by orally dissolving tablets may not be associated with the same degree of weight gain as conventional tablet formulations;[13] however this has not been substantiated in a blinded experimental setting.

Off-label uses

Case-reports, open-label, and small pilot studies suggest efficacy of olanzapine for the treatment of some anxiety spectrum disorders (e. g. generalized anxiety disorder,[14] panic disorder,[15] post-traumatic stress disorder[16]); however, olanzapine has not been rigorously evaluated in randomized, placebo-controlled trials for this use and is not FDA approved for these indications. Generalized anxiety disorder ( GAD) is an Anxiety disorder that is characterized by excessive uncontrollable and often irrational worry about everyday things that Panic Disorder is a Psychological condition characterized by recurring Panic attacks in combination with significant behavioral change lasting at least a month Post traumatic stress disorder It is a severe and ongoing emotional reaction to Other common off-label uses of olanzapine include the treatment of eating disorders (e. g. anorexia nervosa) and as an adjunctive treatment for major depressive disorder without psychotic features. Anorexia Nervosa is a psychiatric Diagnosis that describes an Eating disorder characterized by low Body weight and Body image distortion It has also been used for Tourette's syndrome and stuttering. Tourette syndrome (also called Tourette's syndrome, Tourette's disorder, Gilles de la Tourette syndrome, GTS or more commonly simply Tourette's

Olanzapine has been marketed for dementia by Eli Lilly though it has never been shown to help with the symptoms of dementia. Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline According to internal documents obtained by the New York Times, Lilly instructed its sales representatives to suggest that physicians prescribe Zyprexa to older patients with symptoms of dementia. One such document states "dementia should be first message" for primary care doctors, since they "do not treat bipolar" or schizophrenia, but "do treat dementia". Three months after its launch, Lilly's Zyprexa campaign, called "Viva Zyprexa", led to 49,000 new prescriptions. In 2002, the company changed the name of the primary care campaign to "Zyprexa Limitless" and began to focus on people with mild bipolar disorder who had previously been diagnosed as depressed, despite the fact that Zyprexa has been FDA approved only for the treatment of mania in bipolar disorder, not depression. Mania (from Greek μανία and that from μαίνομαι - mainomai, "to rage to be furious" is a severe medical condition [17]

Use in elderly

Citing an increased risk of stroke, in 2004 the Committee on the Safety of Medicines (CSM) in the UK issued a warning that olanzapine and risperidone, both atypical antipsychotic medications, should not be given to elderly patients with dementia. A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain "MMIV" redirects here For the Modest Mouse album see " Baron von Bullshit Rides Again " The Committee on the Safety of Medicines ( CSM) was an independent advisory committee that for 40 years advised the UK Licensing Authority on the quality efficacy Risperidone (pronounced Ris-PER-ǐ-dōn and sold under the trade name Risperdal in the Netherlands, United States, Canada, the Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline In the U. S. , olanzapine comes with a black box warning for increased risk of death in elderly patients. In the United States, a black box warning (also sometimes called a black label warning or boxed warning) is a type of warning that appears on the Package It is not approved for use in patients with dementia-related psychosis. [18]

Overdose

Symptoms of an overdose include tachycardia, agitation, dysarthria, decreased consciousness and coma. Dysarthria is a motor Speech disorder resulting from neurological injury, characterised by poor articulation (cf Death has been reported after an acute overdose of 450 mg, but also survival after an acute overdose of 1500 mg. [19] There is no specific, known antidote for olanzapine overdose, and even physicians are recommended to call a certified poison control center for information on the treatment of such a case. A poison control center ( PCC) or poison information center ( PIC) is a Medical facility that is able to provide immediate free and expert treatment [19]

PRIME

The Prevention through Risk Identification, Management, and Education (PRIME) study, funded by the National Institute of Mental Health and Eli Lilly, tested the hypothesis that olanzapine might prevent the onset of psychosis in people at very high risk for schizophrenia. The National Institute of Mental Health ( NIMH) is part of the federal government of the United States and the largest research organization in the world specializing in Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn The study examined 60 patients with prodromal schizophrenia, who were at an estimated risk of 36–54% of developing schizophrenia within a year, and treated half with olanzapine and half with placebo. In Medicine, a prodrome is an early non-specific Symptom (or set of symptoms indicating the start of a Disease before specific symptoms occur Placebo is a substance or procedure a patient accepts as medicine or therapy but which has no specific therapeutic activity [20]

In this study, patients receiving olanzapine had a lower risk of progressing to psychosis, although the difference did not reach statistical significance. In Statistics, a result is called statistically significant if it is unlikely to have occurred by Chance. Olanzapine was effective for treating the prodromal symptoms, but was associated with significant weight gain. [21]

Legal

According to a New York Times article published on December 17, 2006,[22] Eli Lilly has engaged in a decade-long effort to play down the health risks of Zyprexa, its best-selling medication for schizophrenia, according to hundreds of internal Lilly documents and e-mail messages among top company managers. Events 546 - Gothic War (535–554: The Ostrogoths of King Totila Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. These documents and e-mail messages were soon made publicly available as a location hidden Tor service[23], and then made available on the public Internet. Tor ( The Onion Router) is a Free software implementation of second-generation Onion routing – a system enabling its users to communicate anonymously Eli Lilly got a temporary restraining order from a US District Court signed on January 4, 2007 to stop the dissemination or downloading of Eli Lilly documents about Zyprexa, and this allowed them to get a few US-based websites to remove them; on January 8, 2007, Judge Jack B. Weinstein refused the Electronic Frontier Foundation's motion to stay his order[24]. An injunction is an Equitable remedy in the form of a Court order, whereby a party is required to do or interact with in certain ways all right or to refrain from Events 46 BC - Titus Labienus defeats Julius Caesar in the Battle of Ruspina. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 871 - Battle of Ashdown - Ethelred of Wessex defeats a Danish invasion army Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Jack B Weinstein (born 1921 Kansas) is a United States federal judge in the Eastern District of New York. The Electronic Frontier Foundation ( EFF) is an international non-profit advocacy and legal organization based in the United States with the stated purpose of being dedicated The documents can now only be downloaded from public Internet sites outside the US. [25][26][27]These health risks include an increased risk for diabetes through Zyprexa's links to obesity and its tendency to raise blood sugar. Blood sugar, used in a physiological context is a misnomer and misleading Zyprexa is Lilly’s top-selling drug, with sales of $4. 2 billion last year.

The documents, given to The New York Times by Jim Gottstein, a lawyer representing mentally ill patients, show that Lilly executives kept important information from doctors about Zyprexa’s links to obesity and its tendency to raise blood sugar — both known risk factors for diabetes. James B "Jim" Gottstein, JD is an Alaska based Lawyer who specializes in business matters and Public land law and is well known as an attorney The Times of London also obtained copies of the documents and reported that as early as October 1998, Lilly considered the risk of drug-induced obesity to be a "top threat" to Zyprexa sales. [28] In another document, dated October 9, 2000, senior Lilly research physician Robert Baker noted that an academic advisory board he belonged to was "quite impressed by the magnitude of weight gain on olanzapine and implications for glucose. Events 768 - Carloman I and Charlemagne are crowned Kings of The Franks. 2000 ( MM) was a Leap year that started on Saturday of the Common Era, in accordance with the Gregorian calendar. "

Lilly’s own published data, which it told its sales representatives to play down in conversations with doctors, has shown that 30 percent of patients taking Zyprexa gain 22 pounds or more after a year on the drug, another study showed 16% of Zyprexa patients gained at least 30kg (66 pounds) in one year, and some patients have reported gaining 100 pounds or more. But Lilly was concerned that Zyprexa’s sales would be hurt if the company was more forthright about the fact that the drug might cause unmanageable weight gain or diabetes, according to the documents, which cover the period 1995 to 2004. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc In 2006, Lilly paid $700 million to settle 8,000 lawsuits from people who said they had developed diabetes or other diseases after taking Zyprexa. Thousands more suits are still pending. [29]

In 2002, British and Japanese regulatory agencies warned that Zyprexa may be linked to diabetes, but even after the FDA issued a similar warning in 2003, Lilly did not publicly disclose their own findings.

Eli Lilly agreed on January 4, 2007 to pay up to $500 million to settle 18,000 lawsuits from people who claimed they developed diabetes or other diseases after taking Zyprexa. Events 46 BC - Titus Labienus defeats Julius Caesar in the Battle of Ruspina. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Including earlier settlements over Zyprexa, Lilly has now agreed to pay at least $1. 2 billion to 28,500 people who claim they were injured by the drug. At least 1,200 suits are still pending, the company said. About 20 million people worldwide have taken Zyprexa since its introduction in 1996. [30]

See also

Note and References

  1. ^ Electronic Orange Book. Antipsychotics are a group of Psychoactive drugs commonly but not exclusively used to treat Psychosis, which is typified by Schizophrenia. Eli Lilly and Company ( is a global Pharmaceutical company and one of the world's largest corporations Eli Lilly and Company is a global Pharmaceutical company and one of the world's largest corporations Food and Drug Administration (April 2007). Retrieved on 2007-05-24. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1218 - The Fifth Crusade leaves Acre for Egypt. 1276 - Magnus Ladulås is crowned
  2. ^ NDA 21-520. Food and Drug Administration (2003-12-24). Year 2003 ( MMIII) was a Common year starting on Wednesday of the Gregorian calendar. Events 563 - The Byzantine church Hagia Sophia in Constantinople is dedicated for the second time after being destroyed by Earthquakes Retrieved on 2007-10-31. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 445 BC – Ezra reads the Book of the Law to the Israelites in Jerusalem (see Nehemiah 91 NLTse
  3. ^ NDA 20-592 / S-019. Food and Drug Administration (2004-01-14). "MMIV" redirects here For the Modest Mouse album see " Baron von Bullshit Rides Again " Events 1129 - Formal approval of the Order of the Templar at the Council of Troyes. Retrieved on 2007-10-31. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 445 BC – Ezra reads the Book of the Law to the Israelites in Jerusalem (see Nehemiah 91 NLTse
  4. ^ Wirshing DA, Wirshing WC, Kysar L, Berisford MA. (1999) Novel antipsychotics: comparison of weight gain liabilities. Journal of Clinical Psychology 60 358-63
  5. ^ Green B (1999) Focus on olanzapine Current Med Res Opin 15 79-85
  6. ^ Fulbright, April R. (2006). "Complete Resolution of Olanzapine-Induced Diabetic Ketoacidosis" (abstract). Journal of Pharmacy Practice 19 (4): 255-258. Thousand Oaks, CA: SAGE Publications. Thousand Oaks, commonly referred to as "TO" by residents is a city in southeastern Ventura County, California, in the United States. SAGE is an independent for-profit academic Publisher of books more than 500 Journals, and databases in the humanities social sciences and scientific doi:10.1177/0897190006294180. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. “Olanzapine has been associated with diabetic ketoacidosis and also with weight gain, lipid abnormalities, and the development of type 2 diabetes. ” 
  7. ^ Sacher J, et al (2007-08-22). Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 392 - Arbogast has Eugenius elected Western Roman Emperor. "{{{title}}}". Neuropshchopharmacology.  
  8. ^ Sowell, Margaret; et al. (August 8, 2003). Events 1220 - Sweden is defeated by Estonian tribes in the Battle of Lihula. Year 2003 ( MMIII) was a Common year starting on Wednesday of the Gregorian calendar. "Evaluation of Insulin Sensitivity in Healthy Volunteers Treated with Olanzapine, Risperidone, or Placebo: A Prospective, Randomized Study Using the Two-Step Hyperinsulinemic, Euglycemic Clamp". Journal of Clinical Endocrinology & Metabolism 88 (12): 5875-5880. The Endocrine Society. “In summary, this study did not demonstrate significant changes in insulin sensitivity in healthy subjects after 3 wk of treatment with olanzapine or risperidone. ” 
  9. ^ AstraZeneca Pharmaceuticals (04 April 2006). Events 1581 - Francis Drake completes a circumnavigation of the world and is knighted by Elizabeth I. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Efficacy and Tolerability of Olanzapine, Quetiapine and Risperidone in the Treatment of First Episode Psychosis: A Randomized Double Blind 52 Week Comparison. AstraZeneca Clinical Trials. AstraZeneca PLC. AstraZeneca PLC (,) is a large Anglo-Swedish Pharmaceutical company formed on 6 April 1999 by the remerger of Swedish Astra AB Retrieved on 2007-12-03. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1800 - War of the Second Coalition: Battle of Hohenlinden, French  “At week 12, the olanzapine-treated group had more weight gain, a higher increase in [ body mass index ], and a higher proportion of patients with a BMI increase of at least 1 unit compared with the quetiapine and risperidone groups (p<=0. The body mass index ( BMI) or Quetelet index, is a statistical measurement which compares a person's weight and height Quetiapine ( kwe-TYE-a-peen marketed by AstraZeneca as Seroquel and by Orion Pharma as Ketipinor, is an Atypical antipsychotic Risperidone (pronounced Ris-PER-ǐ-dōn and sold under the trade name Risperdal in the Netherlands, United States, Canada, the 01). ”
  10. ^ Moyer, Paula. "CAFE Study Shows Varying Benefits Among Atypical Antipsychotics", Medscape Medical News, WebMD, 2005-10-25. WebMD is a medical and wellness information service primarily known for its public Internet site which provides health information a symptom checklist pharmacy information blogs of Year 2005 ( MMV) was a Common year starting on Saturday (link displays full calendar of the Gregorian calendar. Events 1147 - The Portuguese, under Afonso I, and Crusaders from England and Flanders conquer Lisbon after a Retrieved on 2007-12-03. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1800 - War of the Second Coalition: Battle of Hohenlinden, French  
  11. ^ National Institute of Mental Health (19 September 2005). The National Institute of Mental Health ( NIMH) is part of the federal government of the United States and the largest research organization in the world specializing in Events 335 - Dalmatius is raised to the rank of Caesar by his uncle Constantine I. Year 2005 ( MMV) was a Common year starting on Saturday (link displays full calendar of the Gregorian calendar. "NIMH study to guide treatment choices for schizophrenia". Press release. A news release, media release, press release or press statement is a written or recorded Communication directed at members of the News Retrieved on 2006-12-18. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 218 BC - Second Punic War: Battle of the Trebia - Hannibal 's Carthaginian forces defeat those of the
  12. ^ Carey, Benedict. Benedict Carey (born 1960 is an American journalist and reporter on medical and science topics for The New York Times. "Little Difference Found in Schizophrenia Drugs", New York Times, The New York Times Company, September 20, 2005. Events 451 - The Battle of Chalons takes place in North Eastern France. Year 2005 ( MMV) was a Common year starting on Saturday (link displays full calendar of the Gregorian calendar. Retrieved on 2007-12-03. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1800 - War of the Second Coalition: Battle of Hohenlinden, French  
  13. ^ de Haan L, van Amelsvoort T, Rosien K, Linszen D (2004). "Weight loss after switching from conventional olanzapine tablets to orally disintegrating olanzapine tablets". Psychopharmacology (Berl) 175 (3): 389-90. PMID 15322727.  
  14. ^ Pollack MH, Simon NM, Zalta AK, Worthington JJ, Hoge EA, Mick E, Kinrys G, Oppenheimer J. (2006). "Olanzapine augmentation of fluoxetine for refractory generalized anxiety disorder: a placebo controlled study. ". Biol Psychiatry. 59 (3): 211-5. doi:10.1016/j.biopsych.2005.07.005. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16139813.  
  15. ^ Sepede G, De Berardis D, Gambi F, Campanella D, La Rovere R, D'Amico M, Cicconetti A, Penna L, Peca S, Carano A, Mancini E, Salerno RM, Ferro FM. (2003). "Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial. ". J Clin Psychopharmacol. 107 (5): 394-6. PMID 16415705.  
  16. ^ Jakovljević M, Sagud M, Mihaljević-Peles A. (2006). "Olanzapine in the treatment-resistant, combat-related PTSD--a series of case reports. ". Acta Psychiatrica Scandinavica 26 (1): 45-9. The Acta Psychiatrica Scandinavica is a Scandinavian Peer reviewed Scientific journal containing Original research, Systematic PMID 12752037.  
  17. ^ Berenson, Alex. "Drug Files Show Maker Promoted Unapproved Use", New York Times, The New York Times Company, Dec 18, 2006. Events 218 BC - Second Punic War: Battle of the Trebia - Hannibal 's Carthaginian forces defeat those of the Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Retrieved on 2007-12-03. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1800 - War of the Second Coalition: Battle of Hohenlinden, French  
  18. ^ Important Safety Information for Olanzapine. Zyprexa package insert. Eli Lilly & Company (2007). Retrieved on 2007-12-03. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1800 - War of the Second Coalition: Battle of Hohenlinden, French  “Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. [. . . ] ZYPREXA® (olanzapine) is not approved for the treatment of elderly patients with dementia-related psychosis. ”
  19. ^ a b Symbyax (Olanzapine and fluoxetine) drug overdose and contraindication information. RxList: The Internet Drug Index. WebMD (2007). WebMD is a medical and wellness information service primarily known for its public Internet site which provides health information a symptom checklist pharmacy information blogs of Retrieved on 2007-12-03. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1800 - War of the Second Coalition: Battle of Hohenlinden, French
  20. ^ McGlashan, T.H.; et al. Dr Thomas McGlashan (born 1942 is a professor of Psychiatry at Yale University. (1 May 2003). Events 305 - Diocletian and Maximian retire from the office of Roman Emperor. Year 2003 ( MMIII) was a Common year starting on Wednesday of the Gregorian calendar. "The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design". Schizophrenia Research 61 (1): 7-18. Amsterdam: Elsevier. Amsterdam (pronounced) is the capital and largest city of the Netherlands, located in the province of North Holland in the west Elsevier, the world's largest Publisher of Medical and Scientific literature, forms part of the Reed Elsevier group doi:10.1016/S0920-9964(02)00439-5. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12648731.  
  21. ^ McGlashan, Thomas H.; et al. Dr Thomas McGlashan (born 1942 is a professor of Psychiatry at Yale University. (May 2006). "Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis". American Journal of Psychiatry 163 (5): 790-99. The American Journal of Psychiatry (AJP is the official journal of the American Psychiatric Association (APA and the most widely read and cited Psychiatric Arlington, VA: American Psychiatric Association. The American Psychiatric Association (APA is the main Professional organization of Psychiatrists and trainee psychiatrists in the United States, and the doi:10.1176/appi.ajp.163.5.790. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16648318.  
  22. ^ [http://www.nytimes.com/2006/12/17/business/17drug.html The New York Times December 17, 2006
  23. ^ The Zyprexa Memos (Requires Tor)
  24. ^ Press Releases: January, 2007 | Electronic Frontier Foundation
  25. ^ ZyprexaKills: Download the documents and memos as multi-page tiff files
  26. ^ Canadian journalist Rob Wipond: Download the documents and memos as multi-page tiff files
  27. ^ Swiss/German web site Boocompany.com: Download or browse the documents and memos as pdf files and OCR-generated searchable ASCII text files
  28. ^ [1] Eli Lilly was Concerned by Zyprexa Side-Effects from 1998, The Times (London), January 23, 2007
  29. ^ [2] Mother Wonders if Psychosis Drug Helped Kill Son, New York Times, January 4, 2007
  30. ^ [3] Lilly to Pay Up to $500 Million to Settle Claims. Events 546 - Gothic War (535–554: The Ostrogoths of King Totila Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Tor ( The Onion Router) is a Free software implementation of second-generation Onion routing – a system enabling its users to communicate anonymously Events 393 - Roman Emperor Theodosius I proclaims his nine year old son Honorius co-emperor Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 46 BC - Titus Labienus defeats Julius Caesar in the Battle of Ruspina. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. The New York Times, January 4, 2007

External links

Manufacturer site

Consumer information

Controversy

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Dictionary

olanzapine

-noun

  1. An antipsychotic drug used to treat schizophrenia and bipolar disease etc
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