Risperidone second-generation effects

The conventional antipsychotics have little effect on the negative psychotic symptoms such as autism, stupor and emotional withdrawal. The so-called atypical antipsychotics, or second-generation antipsychotics, like the heterocyclic compound risperidone, the benzamide sulpiride and several diben-zepines of which clozapine is the best known, have a broader spectrum which means that they also have an effect on the negative psychotic symptoms. Most share a common attribute of working on serotonin receptors as well as dopamine receptors. They have a low risk of extrapyramidal side effects. 

An addition (1994) to the antipsychotic armory is risperidone (Risperdal). Although still a member of the second generation, it may well be a member of its elite because of its alleged ties to both DA, D2 and serotonin type 2 receptors. Histamine and a receptors may also have connections to this agent. The extent of affinities of the latter three, however, are not known. The 9-hydroxy metabolite of risperidone is equally effective. 

A mutual increase in serum levels of both thioridazine and paroxetine is evident when these agents are combined. Paroxetine has also been shown to increase haloperidol and perphenazine serum levels, with associated extrapyramidal side-effects. The mechanism is presumably via inhibition of hepatic enzymes. With respect to the second-generation antipsychotic drugs (SCAs), paroxetine at a dose of 20 mg/daily produces a 3-9-fold elevation in plasma risperidone. If paroxetine is administered with clozapine, mean plasma concentrations of clozapine and norclozapine may increase significantly (by about 30%). 

Johnsen E, Kroken RA, Wentzel-Larsen T, Jorgensen HA. Effectiveness of second-generation antipsychotics a naturalistic, randomized comparison of olanzapine, quetiapine, risperidone, and ziprasidone. BMC Psychiatry 2010 10 26. 

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