INTRODUCTION The purpose of this paper is to inform the risk associated in antipsycotic treatment in schizophrenic patient and also the risk of sudden cardiac death. The paper was inspired by Bruce K Alexander, whose paper does not lose it’s actuality until present. The main research method used was Meta analyses and historical research. Users of typical antipsychotic drugs have an increased risk of serious ventricular arrhythmia’s and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which largely replaced the older agents in clinical practice.
Antipsychotic drugs have become the cornerstone of treatment for schizophrenia. The first-generation “conventional” antipsychotic drugs are high-affinity antagonists of dopamine receptors that are most effective against psychotic symptoms but have high rates of neurologic side effects, such as extrapyramidal signs and tardive dyskinesia. The introduction of second-generation, or”atypical,” antipsychotic drugs promised enhanced efficacy and safety. The atypical agents differ pharmacologically from previous antipsychotic agents in their lower affinity for dopamine receptors and greater affinities for other neuroreceptors, including those for serotonin and norepinephrine.
Although studies indicated that the atypical drugs are similar to the conventional drugs in reducing psychotic symptoms and produce few neurologic effects, the evidence of their superior efficacy has been neither consistent nor robust, with the exception of clozapine, which repeatedly has been effective in patients whose condition is refractory to treatment with other types of agents but has severe side effects that limit its use. The newer agents appear more efficacious than conventional drugs in reducing negative symptoms (e.g., lack of emotion, interest, and expression), possibly owing to the absence of extrapyramidal symptoms or other secondary causes of negative symptoms (e.g., depression) rather than to direct therapeutic effects.
The results of studies of the effects of treatment on cognitive impairment and mood symptoms have been inconclusive. The ability of atypical agents to prevent relapse and their effects on social and vocational functioning, quality of life and long-term outcome have been incompletely explored. The safety advantages of the atypical drugs have been questioned because of their propensity to induce weight gain and alter glucose and lipid metabolism. Nevertheless, these medications are widely used and have a 90 percent market share in the United States, resulting in burgeoning costs. In the wake of this trend, questions have been raised about the clinical advantages and cost effectiveness of the atypical drugs.
This report the primary outcomes of a double-blind, active-control clinical trial sponsored by the National Institute of Mental Health (NIMH) that was designed to compare the effectiveness of atypical and conventional antipsychotic drugs. METHOD INCLUSION CRITERIA I would be including articles that are mainly from reliable source such as PubMed, MDPI and ncbi. Recent study of anti-psychotic treatment in schizophrenic patient, published after 2000 in order to provide relevant information.
I would be also including articles based on research conducted over adequate sample size and having a valid comparison group so that the result of my final research can be generalized. EXCLUTION CRITERIA I would be excluding articles that were published before 2000. I would also be excluding studied conducted on association between second-generation anti-psychotic medications and risk of pneumonia requiring hospitalization in patients with schizophrenia because the evidence is limited in the population. MECHANISM OF ANTIPSYCOTIC ACTION Dopamine D2 receptor antagonism in the brain is a general pharmacodynamic property of all antipsychotics; this has given rise to the hypothesis that schizophrenia involves a dysregulation of dopaminergic circuits with excess dopaminergic activity in the mesolimbic pathway (leading to positive symptoms of psychosis) and reduced dopaminergic signalling in the mesocortical pathway (leading to negative symptoms). Evidence for the dopamine hypothesis comes from not only the efficacy of D2 receptor antagonists, but also through the effects of D2 agonists such as amphetamine in precipitating psychosis and the effects of dopamine-depleting drugs such as reserpine in reducing psychotic symptoms.Antipsychotic action has consistently been shown to occur when the occupation of striatal D2 receptors is more than 65%, but further increases in the level of D2 blockade are not associated with improved antipsychotic efficacy; rather, it leads to the onset of side effects such as EPSEs and hyperprolactinaemia.
A threshold dose for EPSEs occurs when ?80% of the D2 receptors are occupied and for hyperprolactinaemia when D2 blockade exceeds 72%. Despite the association of striatal dopamine blockade with the risk of EPSEs, it is important to note that this is not the critical site of action for therapeutic effect, which occurs most prominently in the mesolimbic brain system. ANTIPSYCOTIC MEDICATION AND ADVERSE EFFECTIn Leuchts meta-analysis, amisulpride proved to be the best in terms of tolerability, with less discontinuation due to side effects compared with placebo.
Haloperidol was the worst drug for discontinuation rates compared with placebo. Haloperidol was identified as the medication most likely to cause EPSEs, while weight gain and metabolic dysfunction were most notably identified with the use of olanzapine and clozapine (and to a lesser extent with risperidone and quetiapine),findings that have been consistently replicated in other studies. CARDIOMETABOLIC ADVERSE EFFECTHigher rates of modifiable cardiovascular risk factors are seen in schizophrenic patient, with 33% of patients with schizophrenia meeting the criteria for metabolic syndrome throughout the course of the illness.
The increased risk for cardiometabolic risk factors is multifactorial with genetic factors and the cumulative long-term effect of poor health behaviours and long-term exposure to antipsychotic drug postulated as causes. SGAs are associated with higher rates of metabolic dysfunction compared with FGAs. Clozapine and olanzapine both have the greatest affinity for 5-HT2C and Histamine 1 receptors and the greatest weight gain potential, which can occur early in the course of treatment, before plateauing as the treatment continues. The most dramatic weight gain is seen in antipsychotic naive patients over the first 6 weeks of treatment and for the majority, those with initial weight gain did not lose that weight thereafter, even after switching to more weight-neutral antipsychotics.
SGAs such as aripiprazole, lurasidone and asenapine have a more neutral metabolic side effect profile. RESULT The primary cohort included 93,300 users of antipsychotic drugs and 186,600 matched controls. There were 44,218 and 46,089 users of single typical and atypical antipsychotic drugs, respectively, at cohort entry. The cohort that was matched for propensity score included 67,824 users of antipsychotic drugs and 116,069 nonusers As compared with users of typical antipsychotic drugs, users of atypical antipsychotic drugs were slightly younger, were less likely to be enrolled in Medicaid because of disability, and had a higher baseline cardiovascular risk score.
They also used higher doses of antipsychotic drugs, in part owing to the preponderance of low-dose use for the typical drug thioridazine. Users of atypical antipsychotic drugs also were likely to have a diagnosis of schizophrenia than were users of typical antipsychotic drugs. The research was completed according to the pre-specified plan without any deviation from the exact research idea. CONCLUSION In conclusion, the patients with chronic schizophrenia in this study discontinued their antipsychotic study medications at a high rate, indicating substantial limitations in the effectiveness of the drugs. Within this limited range of effectiveness, olanzapine appeared to be more effective than the other drugs studied, and there were no significant differences in effectiveness between the conventional drug and the other second-generation drugs.
However, olanzapine was associated with greater weight gain and increases in glycosylated hemoglobin, cholesterol, and triglycerides, changes that may have serious implications with respect to medical comorbidity such as the development of the metabolic syndrome. Current users of typical antipsychotic drugs and of atypical antipsychotic drugs in the study cohort had a similar dose-related increased risk of sudden cardiac death. This finding suggest that with regard to this adverse effect, the atypical antipsychotic drugs are no safe than the older drugs. REFERENCES 1. https://www.ncbi.
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