to be mediated by the following mechanisms: - Causing weight gain by antagonizing the histamine H1 and serotonin 5-HT2Creceptors and perhaps by interacting with other neurochemical pathways in the central nervous system. Neuroleptic malignant syndrome, a potentially fatal condition characterized by: - Autonomic instability, which can manifest with tachycardia, nausea, vomiting, diaphoresis, etc. - Hyperthermia — elevated body temperature. - Mental status change (confusion, hallucinations, coma, etc.) - Muscle rigidity - Laboratory abnormalities (e.g., elevated creatine kinase, reduced iron plasma levels, electrolyte abnormalities, etc.) Pancreatitis QT interval prolongation — more prominent in those treated with amisulpride, pimozide, sertindole, thioridazine and ziprasidone. Torsades de pointes Seizures, particularly in people treated with chlorpromazine and clozapine. Thromboembolism Myocardial infarction Stroke Long-term effects Some studies have found decreased life expectancy associated with the use of antipsychotics, and argued that more studies are needed. Antipsychotics may also increase the risk of early death in individuals with dementia. Antipsychotics typically worsen symptoms in people with depersonalisation disorder. Antipsychotic polypharmacy (prescribing two or more antipsychotics at the same time for an individual) is a common practice but not evidence-based or recommended, and there are initiatives to curtail it. Similarly, the use of excessively high doses (often the result of polypharmacy) continues despite clinical guidelines and evidence indicating that it is usually no more effective but is usually more harmful. A meta-analysis of observational studies with over two million individuals has suggested a moderate association of antipsychotic use with breast cancer. Loss of grey matter and other brain structural changes over time are observed amongst people diagnosed with schizophrenia. Meta-analyses of the effects of antipsychotic treatment on grey matter volume and the brain's structure have reached conflicting conclusions. A 2012 meta-analysis concluded that grey matter loss is greater in patients treated with first generation antipsychotics relative to those treated with atypicals, and hypothesized a protective effect of atypicals as one possible explanation. A second meta-analysis suggested that treatment with antipsychotics was associated with increased grey matter loss. Animal studies found that monkeys exposed to both first- and second-generation antipsychotics experience significant reduction in brain volume, resulting in an 8-11% reduction in brain volume over a 17–27 month period. The National Association of State Mental Health Program Directors said that antipsychotics are not interchangeable and it is recommend including trying at least one weight-neutral treatment for those patients with potential metabolic issues. Subtle, long-lasting forms of akathisia are often