Generation Antipsychotic Drugs Research Articles

Efficacy Review of Antipsychotics

SUMMARYAntipsychotic drugs have been available for more than 40 years. The invention of neuroleptics changed the overall treatment of schizophrenia dramatically. Nevertheless, the discussion on the importance and role of antipsychotic therapy still goes on1. In the public as well as in the media, there remains a great deal of scepticism about the role of psychopharmacotherapy in the treatment of schizophrenia. The best way to handle this is an evidence-based approach. The efficacy of neuroleptic treatment has been proven in over 150 double-blind, controlled clinical trials. Thesecond generation of antipsychotic drugs show similar antipsychotic properties as the classical agents, but with fewer side-effects such as extrapyramidal symptoms (EPS). The atypical antipsychotic agents have improved the quality of therapy and can also improve and support other aspects of treatment. When used with other treatment strategies, atypical antipsychotic agents could improve the overall outcome of this usually chronic disease. It is now necessary to implement these strategies as effectively as possible.

Treatments for chronic psychosis

Psychosis is a mental condition characterized by hallucinations, delusions, and thought disorder; it spans diagnostic entities that respond to similar therapeutic approaches. Psychosis has no fully described tissue pathology, as vet, but is still identified and assessed symptomatically. The first generation of antipsychotic drugs was developed in the middle of the 20th century. The second generation of drugs arrived in the 1990s. This new group of antipsychotic drugs has potent therapeutic actions on the positive symptoms of psychosis with far fewer side effects, especially motor effects. However, each of the new drugs has its own characteristic clinical and pharmacological features that affect individual patient response. Understanding these individual drug characteristics can promote optimal drug choice and use in conditions of chronic psychosis.

The new generation of antipsychotic drugs: how atypical are they?

The cardinal feature of traditional neuroleptic drugs is extrapyramidal symptoms (EPS), such as parkinsonism, akathisia, and dystonia. Irrespective of the autonomic nervous system side-effect profile of a specific neuroleptic, the entire class produces EPS. Therefore, EPS and antipsychotic activity were once thought to be inextricably linked. However, with the discovery of clozapine, this concept was no longer defensible. Clozapine produced antipsychotic actions without associated EPS or increases in serum prolactin levels, and the term 'atypical' was coined to differentiate its actions from those of the traditional agents. Later, the definition of atypical was expanded to encompass clozapine's unique clinical spectrum of activity, including its effectiveness in treating some patients unresponsive to traditional neuroleptics. Clozapine thus became the archetype for a new generation of antipsychotic drugs, which now includes quetiapine, olanzapine, risperidone, sertindole, ziprasidone, zotepine and amisulpride. This paper will review the pharmacological actions that contribute to the unique features of clozapine, focusing on receptor profile and activity in animal models used for evaluations of antipsychotic activity and EPS. Similarities and differences amongst the new agents will also be discussed. Although conclusions regarding atypicality require controlled clinical trials in addition to preclinical and animal models, it is apparent from this review that not all agents match the profile of clozapine.

Treatment mechanisms: traditional and new antipsychotic drugs

The first generation of antipsychotic drugs was discovered in the 1960s and 1970s, These agents were effective in treating psychosis, but were accompanied by significant side effects, including severe parkinsonism and akathisia. Second-generation antipsychotics were introduced in the 1990s, These drugs have at least equal efficacy to their predecessors, but far fewer side effects. Some data suggest a broader efficacy profile. Clozapine remains the only superior antipsychotic in terms of the magnitude of psychotic symptom reduction. Clinical and animal studies are consistent in suggesting that the antipsychotic component of antidopaminergic treatments is initiated by dopamine receptor blockade in the striatum and that the signal is transmitted to the neocortex through the established basal ganglia-thalamo-cortical neuronal circuits. Other neurotransmitter actions (eg, antiserotonergic) can be exerted locally, in the neocortex. Defining tissue targets of drug action may suggest additional strategies for developing new antipsychotic drugs.

New dimensions in the pharmacologic treatment of schizophrenia and related psychoses.

During the past 5 years unprecedented advances have taken place in the psychopharmacology of schizophrenia and related psychoses. Clozapine and risperidone, two prototypic novel antipsychotic drugs, have had a significant impact on the treatment of psychotic disorders. Additionally, they have ushered in another generation of antipsychotic drugs with complex pharmacologic profiles, potentially enhanced efficacy, and more benign side-effect profiles than previously associated with conventional antipsychotic medications. This review highlights these developments, implications for the management of psychotic disorders, and the use of novel antipsychotic drugs in specific clinical subgroups.

New generation of antipsychotic drugs: Novel mechanisms of action. Edited by N. Brunello, J. Mendlewicz and G. Racagni. Karger, Basel, 1993. ISBN: 3‐8055‐5654‐3

New generation of antipsychotic drugs: Novel mechanisms of action. Edited by N. Brunello, J. Mendlewicz and G. Racagni. Karger, Basel, 1993. ISBN: 3‐8055‐5654‐3

Pharmacologic Advances in the Treatment of Schizophrenia

The treatment of schizophrenia was revolutionized with the introduction of chlorpromaeine in 1952. The effectiveness of chlorpromazine in controlling psychotic symptoms lead to the dopamine Hypothesis of schizophrenia, which revolutionized our conceptualization of this illness. Since that time, numerous typical antipsychotic drugs have been developed for the treatment of schizophrenia. However, the introduction of clozapine in 1990 began a new era in the pharmacologic management of schizophrenia. Clozapine, an atypical antipsychotic drug, is effective in controlling the positive Symptoms of schizophrenia in a large number of otherwise treatment-resistant patients, and also improves the negative symptoms of the illness in marry patients. Clozapine is classified as an atypical antipsychotic drug because it has little potential for causing extrapyramidal side effects, and its effects on dopaminergic and serotonergic neurotransmitter systems are unique compared with those of typical antipsychotic medications. The effectiveness of clozapine and the explosion of research in neuroscience has led to the investigation of neurotransmitter systems other than dopamine as important in developing pharmacologic strategies for the treatment of schizophrenia. This paper will review current pharmacologic advances in the treatment of schizophrenia, and highlight the clinical findings and use of clozapine, the prototype of a new generation of antipsychotic drugs.