Оланзапин: Эффективность, побочные эффекты и применение при психических расстройствах.

Atypical antipsychotic medication

The first line psychiatric treatment for schizophrenia is antipsychotic medication. Olanzapine appears to be effective in reducing symptoms of schizophrenia, treating acute exacerbations, and treating early onset schizophrenia. The usefulness of maintenance therapy, however, is difficult to determine, as more than half of people in trials quit before the 6 week completion date. Treatment with olanzapine (like clozapine) may result in increased weight gain and increased glucose and cholesterol levels when compared to most other second generation antipsychotic drugs used to treat schizophrenia.

Olanzapine is recommended by the National Institute for Health and Care Excellence as a first line therapy for the treatment of acute mania in bipolar disorder. It is recommended in combination with fluoxetine as a first line therapy for acute bipolar depression, and as a second line treatment by itself for the maintenance treatment of bipolar disorder. The Network for Mood and Anxiety Treatments recommends olanzapine as a first line maintenance treatment in bipolar disorder and the combination of olanzapine with fluoxetine as second line treatment for bipolar depression. A review on the efficacy of olanzapine as maintenance therapy in people with bipolar disorder was published by in 2006. A 2014 meta analysis concluded that olanzapine with fluoxetine was the most effective among nine treatments for bipolar depression included in the analysis.

Olanzapine is associated with the highest placental exposure of any atypical antipsychotic. Despite this, the available evidence suggests it is safe during pregnancy, although the evidence is insufficiently strong to say anything with a high degree of confidence. Breastfeeding in women taking olanzapine is advised against because olanzapine is secreted in breast milk, with one study finding that the exposure to the infant is about 1.8% that of the mother. A BBC investigation in June 2008 found that this advice was being widely ignored by British doctors. Evidence suggested that the elderly are more likely to experience weight gain on olanzapine compared to aripiprazole and risperidone.

The principal side effect of olanzapine is weight gain, which may be profound in some cases and/or associated with derangement in blood lipid and blood sugar profiles (see section metabolic effects). A 2013 meta analysis of the efficacy and tolerance of 15 antipsychotic drugs (APDs) found that it had the highest propensity for causing weight gain out of the 15 APDs compared with an SMD of 0.74. but may include tremors and muscle rigidity. Aripiprazole, asenapine, clozapine, quetiapine and olanzapine, in comparison to other antipsychotic drugs, are less frequently associated with hyperprolactinaemia. Although these drugs can cause transient or sustained hyperprolactinaemia, the risk is much lower. Owing to its partial dopaminergic agonist effect, aripiprazole is likely to reduce prolactin levels and, in some patients, can cause hypoprolactinaemia. Although olanzapine causes an early dose related rise in prolactin, this is less frequent and less marked than that seen with haloperidol, and is usually transient. A rise in prolactin is seen in about half of patients on olanzapine compared to over 90% of those taking risperidone, and enduring increases were less frequent in those taking olanzapine. It is not recommended to be used by IM injection in acute myocardial infarction, bradycardia, recent heart surgery, severe hypotension, sick sinus syndrome, and unstable angina. Several patient groups are at a heightened risk of side effects from olanzapine and antipsychotics in general. Olanzapine may produce nontrivial high blood sugar in people with diabetes mellitus. Likewise, the elderly are at a greater risk of falls and accidental injury. Young males appear to be at heightened risk of dystonic reactions, although these are relatively rare with olanzapine. Most antipsychotics, including olanzapine, may disrupt the body's natural thermoregulatory systems, thus permitting excursions to dangerous levels when situations (exposure to heat, strenuous exercise) occur. Other side effects include galactorrhea, amenorrhea, gynecomastia, and erectile dysfunction (impotence).

Many different types of medication can create or induce pure obsessive compulsive disorder (OCD) in patients who have never had symptoms before. A new chapter about OCD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (2013) now specifically includes drug induced OCD.

The US Food and Drug Administration (FDA) requires all atypical antipsychotics to include a warning about the risk of developing hyperglycemia and diabetes, both of which are factors in the metabolic syndrome. These effects may be related to the drugs' ability to induce weight gain, although some reports have been made of metabolic changes in the absence of weight gain. Studies have indicated that olanzapine carries a greater risk of causing and exacerbating diabetes than another commonly prescribed atypical antipsychotic, risperidone. Of all the atypical antipsychotics, olanzapine is one of the most likely to induce weight gain based on various measures. The effect is dose dependent in humans and animal models of olanzapine induced metabolic side effects. There are some case reports of olanzapine induced diabetic ketoacidosis. Olanzapine may decrease insulin sensitivity, though one 3 week study seems to refute this. It may also increase triglyceride levels. One small, open label, nonrandomized study suggests that taking olanzapine by orally dissolving tablets may induce less weight gain, but this has not been substantiated in a blinded experimental setting.

Postinjection delirium/sedation syndrome (PDSS) is a rare syndrome that is specific to the long acting injectable formulation of olanzapine, olanzapine pamoate. The incidence of PDSS with olanzapine pamoate is estimated to be 0.07% of administrations, and is unique among other second generation, long acting antipsychotics (e. g. paliperidone palmitate), which do not appear to carry the same risk.

Olanzapine is metabolized by the cytochrome P450 (CYP) system; principally by isozyme 1A2 (CYP1A2) and to a lesser extent by CYP2D6. By these mechanisms, more than 40% of the oral dose, on average, is removed by the hepatic first pass effect. Clearance of olanzapine also varies by race; in self identified African Americans or Blacks, olanzapine's clearance was 26% higher.

The preparation of olanzapine was first disclosed in a series of patents from Eli Lilly & Co. in the 1990s. In the final two steps, 5 methyl 2 [(2 nitrophenyl)amino] 3 thiophenecarbonitrile was reduced with stannous chloride in ethanol to give the substituted thienobenzodiazepine ring system, and this was treated with methylpiperazine in a mixture of dimethyl sulfoxide and toluene as solvent to produce the drug.

Eli Lilly has faced many lawsuits from people who claimed they developed diabetes or other diseases after taking Zyprexa, as well as by various governmental entities, insurance companies, and others. Lilly produced a large number of documents as part of the discovery phase of this litigation, which started in 2004; the documents were ruled to be confidential by a judge and placed under seal, and later themselves became the subject of litigation. and in early 2007, Lilly settled around 18,000 suits for $500 million, which brought the total Lilly had paid to settle suits related to the drug to $1.2 billion. The company denied these allegations and stated that the article had been based on cherry picked documents. in 2007 Lilly filed a protection order to stop the dissemination of some of the documents, which Judge Jack B. Weinstein of the Brooklyn Federal District Court granted. Judge Weinstein also criticized the New York Times reporter, Gottstein, and Egilman in the ruling. On 9 October 2000, senior Lilly research physician Robert Baker noted that an academic advisory board to which he belonged was "quite impressed by the magnitude of weight gain on olanzapine and implications for glucose." In September 2008, Judge Weinstein issued an order to make public Lilly's internal documents about the drug in a different suit brought by insurance companies, pension funds, and other payors. In March 2008, Lilly settled a suit with the state of Alaska, and in October 2008, Lilly agreed to pay $62 million to 32 states and the District of Columbia to settle suits brought under state consumer protection laws. The outcomes described here, and their legal ramifications, were fueled by motions and appeals that were not resolved until 2010. In 2021, Gottstein summarized this tangle of legal activities, and their impact on the political landscape of psychiatry and antipsychiatry in the US, in The Zyprexa Papers.