X hits on this document

Word document

The usefulness and use of second-generation - page 18 / 81





18 / 81

Children and adolescents appear to be at higher risk for weight gain on risperidone than adults. This was found by Hellings et al. [57] in mentally retarded and autistic patients and by Martin et al. [58] in a retrospective chart review of 37 child and adolescent in-patients. Over a 6-month observation period, these authors found that weight increased at an average rate of 1,2 kg/month.  Markianos et al. [59], who studied the effects of a number of FGAMs and SGAMs on prolactin levels, concluded that risperidone had a greater propensity to increase prolactin levels than haloperidol. They also found that clozapine and olanzapine (in that order) brought less risk of increased prolactin than risperidone.


Pezawas et al. [60] have added to the available information on the propensity of sertindole to prolong the QTc interval.  In a drug-surveillance study of 34 co-morbid and co-medicated sertindole-treated patients, they found a mean QTc interval prolongation of 19.7 ms without any evidence of cardiac dysrhythmia.

The suspension for sertindole in Europe has been lifted, and the producers (Lundbeck, Copenhagen, Denmark) of the medication have initiated two large-scale, international, post-marketing surveillance studies which will include all patients for whom sertindole is  prescribed from mid-2002 onwards.


A recent study, as yet unpublished but available on the Food and Drug Administration website (http://www.fda.gov), has produced evidence that ziprasidone induces a mean prolongation of the QTc interval of 20.3 ms at the time of maximum drug blood level. This is a larger increase than that induced by haloperidol, risperidone, olanzapine or quetiapine, though thioridazine led to a considerably larger QT prolongation (35.6 ms). Only 2 out of 2988 patients (0.06 %) who received ziprasidone in placebo-controlled clinical trials revealed QT intervals above the threshold of 500 ms considered clinically relevant by the Food and Drug Administration. One out of 440 (0.23 %) of the placebo-treated patients crossed this threshold.  To date there is no clinical correlate for propensity of ziprasidone to prolong the QT interval, since none of the published studies have found relevant increases in cardiac arrhythmias or an excess risk for unexplained sudden death in patients receiving ziprasidone. None of the countries in which ziprasidone has been licensed requires electrocardiogram monitoring,  but all package inserts provide a clear statement that ziprasidone is not to be used in patients with a known history of QT prolongation, with recent acute myocardial infarction or with uncompensated heart failure. Ziprasidone should not be taken concomitantly with other medications that are known to influence the QT interval, such as quinidine, pimozide, sotalol, thioridazine and sparfloxacin (this is not a complete list).

A review on antipsychotic drugs, cardiac safety and sudden death was published by Glassman and Bigger in 2001 [61]. This review and the report from a policy conference of the European Society of Cardiology on the potential for QT prolongation and proarrhythmia by non-antiarrhythmia drugs (clinical and regulatory implications) [62] provide a useful framework within which to assess the cardiac safety of antipsychotic drugs.

Document info
Document views335
Page views335
Page last viewedTue Jan 24 10:07:17 UTC 2017