Schizophrenia atypical neuroleptics

How the atypical neuroleptics achieve this differential effect is less clear but they could achieve some control of schizophrenia without producing EPSs by ... 

Figure 17.9 Schematic representation of the proposed activity profile of an ideal neuroleptic. The figure shows DA pathways to the prefrontal cortex, mesolimbic nucleus accumbens and striatum the effects required for an ideal drug on the DA influence and symptoms there and to what extent they are met by most typical and atypical neuroleptics and by clozapine. Note that while all atypical neuroleptics induce few extrapyramidal w side-effects (EPSs) few of them, apart from clozapine, have much beneficial effect in overcoming negative symptoms of schizophrenia ...

Bantick RA, Deakin JFW and Grasby PM (2001). The 5-HTia receptor in schizophrenia Promising target for novel atypical neuroleptics. Journal of Psychopharmacology, 15, 37-46. 

Sernyak MJ, Leshe DL, Alarcon RD, et al. Association of diabetes meUitus with atypical neuroleptics in the treatment of schizophrenia. Am Psychiatry 2002 159 561-6. 

Atypical neuroleptics. Because of the limited effectiveness and safety of conventional neuroleptics in TS, clinicians have turned to a new generation of neuroleptics that have been introduced for the treatment of schizophrenia. Risperidone, a member of a class of antipsychotics that blocks both DA and serotonin receptors, has been established as superior to placebo and equal, or superior, to haloperidol in the treatment of schizophrenia (Chouinard et al. 1993 Marder and Meibach 1994]. Risperidone has a more favorable side-effect profile than that of conventional neuroleptics and may have less potential for producing tardive dyskinesia. Compared with haloperidol, fewer extrapyramidal side effects are observed with risperidone in doses of 6 mg/ day or less. As encouraging reports appear in the literature (Lombroso et al. 1995 Stamenkovic et al. 1994 van der Linden et al. 1994], risperidone is currently being widely used by clinicians to treat tic disorders. 

Utman RE, Su TP, Potter WZ, et al Idazoxan and response to typical neuroleptics in treatment-resistant schizophrenia comparison with the atypical neuroleptic, clozapine. Br J Psychiatry 168 571-579, 1996 Uttle A, Levy R, Chuaqui-Kidd P, et al A double-blind placebo-controlled trial of high-dose lecithin in Alzheimer s disease. J Neurol Neurosurg Psychiatry 12 110-118, 1985... 

The atypical neuroleptics—or new generation neuroleptics—cause fewer adverse side effects, are more effective in managing the symptoms of schizophrenia, and are effective for the treatment of bipolar disorder with or without psychosis. However, these drugs are cost more than the older medications. The five approved in the United States as of 2002 are ... 

It may be concluded that despite the importance of the dopamine hypothesis of schizophrenia in serving to unify the mechanism of action of both typical and atypical neuroleptics, it is apparent that some serotonin receptor subtypes, and glutamate receptors of the NMDA subtype, may also play a crucial role. 

In CONCLUSION, the use of the "classical" neuroleptics, as exemplified by the phenothiazines, thioxanthines, butyrophenones and diphenylbutyl-piperidines, has been a landmark in the pharmacotherapy of schizophrenia and psychotic disorders. The efficacy of such drugs in the alleviation of the symptoms of schizophrenia is universally accepted. However, it is also evident that they have a spectrum of adverse effects that frequently renders their long-term use problematic. Side effects such as akathisia, Parkinsonism, tardive dyskinesia and the all too frequent changes in peripheral autonomic activity are largely predictable from the structure of the molecules and the basic animal pharmacology data. Such adverse effects, and the difficulties encountered when attempting to reduce their frequency and severity by concurrent medication, has stimulated the development of "atypical" neuroleptics such as clozapine and risperidone which, hopefully, will combine efficacy with a reduction in side effects. 

Bantick RA, Deakin JF, Grasby PM. The 5-HT1A receptor in schizophrenia a promising target for novel atypical neuroleptics J Psychopharmacol 2001 15(1) 37—46. 

Despite the preponderance of data correlating the dopamine D2 receptor with schizophrenia, alternative sites in the brain (serotonergic, adrenergic, glutamatergic, and GABAergic) are also being investigated to explain the actions of atypical neuroleptics. 

In 2005, an NIMH multisite study called CATIE compared the older neuroleptic perphenazine (Trilafon) and atypical neuroleptics olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), and zipra-sidone (Geodon Lieberman et al., 2005a see also Nasrallah, 2007 Rosenheck et al., 2006 Weiden, 2007a). Phase I involved 1,460 patients diagnosed with schizophrenia initially randomly assigned in a doubleblind study to one of the five neuroleptics. The study lasted 18 months, with safety and tolerability outcomes evaluated at 1, 3, 6, 9, 12, 15, and 18 months. 

Szulc A, Galinska B, Tarasow E, Kubas B, Dzienis W, et al. 2007. N-acetylaspartate (naa) levels in selected areas of the brain in patients with chronic schizophrenia treated with typical and atypical neuroleptics A proton magnetic resonance spectroscopy (lh mrs) study. Med Sci Monit 13 Suppl 1 17-22. 

There have been systematic reviews from the Cochrane Collaboration (www.cochrane.org.uk) of head-to-head comparisons of atypical neuroleptic drugs in non-treatment-resistant schizophrenia. 

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