Olanzapine
From Wikipedia, the free encyclopedia
(Redirected from Zyprexa)
Zyprexa 10 mg tablets (AU)
[edit] Indications and Usage
- oral formulation: acute and maintenance treatment of schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder (monotherapy and in combination with lithium or valproate)
- intramuscular formulation: acute agitation associated with schizophrenia and bipolar I mania in adults
- oral formulation combined with fluoxetine: treatment of acute depressive episodes associated with bipolar I disorder in adults, or treatment of acute, resistant depression in adults [5]
Known FDA approvals are as follows:
- approved for the treatment of the manifestations of psychotic disorders on September 6, 1996[6]
- approved in combination with fluoxetine for the treatment of depressive episodes associated with Bipolar disorder on December 24, 2003[7]
- approved for the long-term treatment of bipolar I disorder on January 14, 2004[8]
- approved in combination with fluoxetine for treatment of resistant depression on March 19, 2009.[9]
[edit] 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,[10] panic disorder,[11] post-traumatic stress disorder);[12] however, olanzapine has not been rigorously evaluated in randomized, placebo-controlled trials for this use and is not FDA approved for these indications. 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. It has also been used for Tourette syndrome and stuttering.[13][14] Olanzapine is also used in many addiction clinics as a sleep aid (usually 2.5–5 mg) due to its low abuse profile and zero addictive properties.
[edit] Prevention of psychosis
Olanzapine has been considered as part of an early psychosis approach for schizophrenia. 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 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.[15] In this study, patients receiving olanzapine had a lower risk of progressing to psychosis, although the difference did not reach statistical significance. Olanzapine was effective for treating the prodromal symptoms, but was associated with significant weight gain.[16]
[edit] 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. In the U.S., olanzapine comes with a black box warning for increased risk of death in elderly patients. It is not approved for use in patients with dementia-related psychosis.[17][18]
However, a BBC investigation in June 2008 found that this advice was being widely ignored by British doctors.
Antipsychotics
From Wikipedia, the free encyclopedia
An antipsychotic (or neuroleptic) is a tranquilizing psychiatric medication primarily used to manage psychosis (including delusions or hallucinations, as well as disordered thought), particularly in schizophreniabipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s. Most of the drugs in the second generation, known as atypical antipsychotics, have been developed more recently, although the first atypical antipsychotic, clozapine, was discovered in the 1950s and introduced clinically in the 1970s. Both generations of medication tend to block receptors in the brain’s dopamine pathways, but antipsychotic drugs encompass a wide range of receptor targets. and
A number of harmful and undesired (adverse) effects have been observed, including lowered life expectancy, weight gain, enlarged breasts and milk discharge in men and women (hyperprolactinaemia), lowered white blood cell count (agranulocytosis), involuntary repetitive body movements (tardive dyskinesia), diabetes, an inability to sit still or remain motionless (tardive akathisia), sexual dysfunction, a return of psychosis requiring increasing the dosage due to cells producing more neurochemicals to compensate for the drugs (tardive psychosis), and a potential for permanent chemical dependence leading to psychosis much worse than before treatment began, if the drug dosage is ever lowered or stopped (tardive dysphrenia).
Temporary withdrawal symptoms including insomnia, agitation, psychosis, and motor disorders may occur during dosage reduction of antipsychotics, and can be mistaken for a return of the underlying condition.[1][2]
History
The original antipsychotic drugs were happened upon largely by chance and then tested for their effectiveness. The first, chlorpromazine, was developed as a surgical anesthetic. It was first used on psychiatric patients because of its powerful calming effect; at the time it was regarded as a “chemical lobotomy“. Lobotomy at the time was used to treat many behavioral disorders, including psychosis, although its effect was to markedly reduce behavior and mental functioning of all types. However, chlorpromazine proved to reduce the effects of psychosis in a more effective and specific manner than the extreme lobotomy-like sedation it was known for. The underlying neurochemistry involved has since been studied in detail, and subsequent antipsychotic drugs have been discovered by an approach that incorporates this sort of information.
Drug action
All antipsychotic drugs tend to block D2 receptors in the dopamine pathways of the brain. This means that dopamine released in these pathways has less effect. Excess release of dopamine in the mesolimbic pathway has been linked to psychotic experiences. It is the blockade of dopamine receptors in this pathway that is thought to control psychotic experiences.
Typical antipsychotics are not particularly selective and also block dopamine receptors in the mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects that the typical antipsychotics can produce (see below). They were commonly classified on a spectrum of low potency to high potency, where potency referred to the ability of the drug to bind to dopamine receptors, and not to the effectiveness of the drug. High-potency antipsychotics such as haloperidol, in general, have doses of a few milligrams and cause less sleepiness and calming effects than low-potency antipsychotics such as chlorpromazine and thioridazine, which have dosages of several hundred milligrams. The latter have a greater degree of anticholinergic and antihistaminergic activity, which can counteract dopamine-related side effects.
Atypical antipsychotic drugs have a similar blocking effect on D2 receptors. Some also block or partially block serotonin receptors (particularly 5HT2A, C and 5HT1A receptors):ranging from risperidone, which acts overwhelmingly on serotonin receptors, to amisulpride, which has no serotonergic activity. The additional effects on serotonin receptors may be why some of them can benefit the “negative symptoms” of schizophrenia.[74]
Controversy
Use of this class of drugs has a history of criticism in residential care. As the drugs used can make patients calmer and more compliant, critics claim that the drugs can be overused. Outside doctors can feel under pressure from care home staff.[81] In an official review commissioned by UK government ministers it was reported that the needless use of anti-psychotic medication in dementia care was widespread and was linked to 1800 deaths per year.[82][83] In the US, the government has initiated legal action against the pharmaceutical company Johnson and Johnson for allegedly paying kickbacks to Omnicare to promote its antipsychotic Risperidone (Risperdal) in nursing homes.[84]
There is some controversy over maintenance therapy for schizophrenia.[2][85] A review of studies about maintenance therapy concluded that long-term antipsychotic treatment was superior to placebo in reducing relapse in individuals with schizophrenia, although some of the studies were small.[86] A review of major longitudinal studies in North America found that a moderate number of patients with schizophrenia were seen to recover over time from their symptoms, raising the possibility that some patients may not require maintenance medication.[85] It has also been argued that much of the research into long-term antipsychotic maintenance may be flawed due to failure to take into account the role of antipsychotic withdrawal effects on relapse rates.[2]
There has also been controversy about the role of pharmaceutical companies in marketing and promoting antipsychotics, including allegations of downplaying or covering up adverse effects, expanding the number of conditions or illegally promoting off-label usage; influencing drug trials (or their publication) to try to show that the expensive and profitable newer atypicals were superior to the older cheaper typicals that were out of patent. For example in the US, Eli Lilly recently pleaded guilty to violating US laws for over a decade in regard to Zyprexa (olanzapine), and was ordered to pay $1.42 billion to settle criminal and civil allegations, including the biggest criminal fine for an individual corporation ever imposed in US history; while Astrazeneca Seroquel (quetiapine), amidst federal investigations of its marketing practices.[87] By expanding the conditions for which they were indicated, Astrazeneca’s Seroquel and Eli Lilly’s Zyprexa had become the biggest selling antipsychotics in 2008 with global sales of $5.5 billion and $5.4 billion respectively.[11] is facing about 9,000 personal-injury lawsuits from more than 15,000 former users of
Some critics have also analyzed the use of alleged front organizations and conflicted patient “advocacy” groups funded by pharmaceutical companies that seek to set the mental health agenda, including the use of the law to force people to take antipsychotics against their will, often justified by claims about risk of violence.[88]
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