Before adding any other medication, or changing to another neuroleptic, a www.selleckchem.com/products/BI6727-Volasertib.html fundamental question should be answered: has the current neuroleptic been optimally used? This question can be divided into two different, questions: has the length of the medication trial been long enough, and has the patient received an optimal dosage? In this presentation, we will focus on the second question: Inhibitors,research,lifescience,medical what is the optimal dosage for the atypical neuroleptics? We will limit the neuroleptics to the atypical agents currently available in the USA (clozapine, risperidone, olanzapine, quetiapine, ziprasidone,

and aripiprazole), and thus we will not discuss dosing issues regarding other atypicals such as sertindole or amisulpride. Lessons from typical neuroleptics The issue of optimal dosage with typical neuroleptics has been the focus of frequent,

debates. For example, in the seventies, very high doses of haloperidol were routinely used. However, it became clear that high doses can Inhibitors,research,lifescience,medical lead to more side effects and particularly to more extrapyramidal side effects (EPS). In the nineties, an opposite trend arose: it was considered that, much lower doses than 30 mg/day were sufficient, to obtain optimal efficacy. This was supported by positron emission tomography (PET) studies that, showed that small daily doses such as 5 mg were sufficient, to obtain more then 60% blockade of the dopamine D2 receptors in the basal Inhibitors,research,lifescience,medical ganglia. Consequently, the average daily dosage of typical neuroleptics has decreased in clinical settings and in clinical research trials (eg, when haloperidol is used as a comparative treatment arm). One remaining issue is to

identify patients who may need higher doses. Although it is commonly accepted Inhibitors,research,lifescience,medical that fast mctabolizcrs need higher doses, there is very little evidence to support, the use of high doses in other circumstances. Inhibitors,research,lifescience,medical Clinicians tend to increase neuroleptic doses, and sometimes up to high doses, for breakthrough symptoms and for a partial response. One study1 found that patients who receive high doses of typical neuroleptics tend to show a more severe course of illness and more persistent symptoms, and some had a history of violence or regressed behavior. Drug_discovery What doses do clinicians prescribe? In the USA, clinical use of atypicals began in 1989 with clozapine. At that, time, it was commonly accepted that, the average daily dose should be around 500 to 600 mg. It is of note that, in the last 5 years, selleck chemicals llc publications report, that, in Europe the average daily dose of clozapine has been much lower (around or below 300 mg), and at the same time, the average daily dose of clozapine has decreased in the USA, as seen in psychiatric hospitals operated by the State of New York (Table I).2 State hospitals in the USA are dedicated to the treatment of people with mental illness who have minimal or no insurance, and who need longer hospital stays.