Risperidone drug administration

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

Risperdal was first marketed in 1994 as an atypical neuroleptic. The clinical trials, most of which lasted a few weeks, were too short to determine the rate of tardive dyskinesia and many other adverse effects. Indeed, the brief controlled clinical trials used for the approval of both clozapine and risperidone do not provide sufficient information to determine either efficacy or safety since the drugs would be used for months and years in individual patients, rather than for a few weeks (see chapter 13). Patients taking the medications over the coming years will provide the experimental data. However, since Risperdal is a potent dopamine blocker, it should have been anticipated that it would cause similar adverse reactions as the older neuroleptics. In my own experience, I have evaluated many cases of tardive dyskinesia caused by Risperdal, Zyprexa, and Geodon. Meanwhile, the Food and Drug Administration (FDA) has required the same tardive dyskinesia and neuroleptic malignant syndrome warnings on the labels of clozapine and risperidone as on the labels of the older neuroleptics. 

The U.S. Food and Drug Administration today approved Risperdal (risperidone) for the treatment of schizophrenia in adolescents, ages 13 to 17, and for the short-term treatment of manic or mixed episodes of bipolar I disorder in children and adolescents ages 10 to 17. This is the first FDA approval of an atypical antipsychotic drug to treat either disorder in these age groups. 

US Food and Drug Administration. 2003 Safety alert RISPERDAL (risperidone). http //www.fda. gov./med-watch/S AFETY/2003/risperdal.htm... 

Adults with autistic disorder (n = 17) or pervasive developmental disorder not otherwise specified (n = 14) participated in a randomized, 12-week, double-blind, placebo-controlled trial of risperidone (41). Among those who completed the study, risperidone (n = 14) was superior to placebo (n = 16) in reducing the symptoms of autism, and the most prominent adverse effect was mild transient sedation during the initial phase of drug administration. Abnormal gait was reported in one patient taking risperidone. 

Iloperidone is a novel antipsychotic drug which is a mixed dopamine D2/serotonin 5-HT2A receptor antagonist. In 2008, the US Food and Drug Administration required Vanda Pharmaceuticals, the manufacturers, to carry out a comparison of iloperidone with placebo and an active comparator such as olanzapine or risperidone [80 ]. It was finally approved in the USA in May 2009. 

Paliperidone, or 9-hydroxyrisperidone, is the major active metabolite of risperidone. It binds to both dopamine Dj and serotonin 5-HT2A receptors, and antagonism at these receptors is thought to account for its therapeutic activity in schizophrenia. It was approved by the US Food and Drug Administration in 2007 for acute and maintenance treatment of schizophrenia it is available in modified-release tablets. The available literature on the pharmacodynamics, pharmacokinetics, clinical efficacy, and tolerability of paliperidone has been extensively reviewed [101 ]. 

Although the neuroleptic malignant syndrome has been reported in patients taking these atypical neuroleptic drugs, it is less common than in patients taking typical neuroleptic drugs, and lithium may have increased the risk in these cases. Co-administration of lithium and risperidone has been associated with the rabbit syndrome (638), but this reaction was probably caused by the risperidone, and the role of lithium was not clear. 

Systemic administration of classical antipsychotics or clozapine block amphetamine-induced discriminative stimulus responses in the rat (205,206). The amphetamine response can also be blocked by direct injection of the drug into the nucleus accumbens (207). While classical antipsychotics completely inhibit the response, clozapine and olanzapine are somewhat less active, risperidone and remoxipride are weakly active, and sertindole and quetiapine were inactive (208, 209). Based on these findings, it has been proposed that the antagonism of the amphetamine discriminative stimulus response may be an indication of neuroleptic-induced deficit properties (209). Antipsychotic drugs also seem to inhibit the discriminative stimulus effects of hallucinogenic 5-HT agonists like DOI, DOM, and LSD in proportion to their 5-HT antagonist potencies (209-211). 

At steady state, venlafaxine weakly inhibits the metabolism of risperidone however, this interaction is unlikely to be of clinical significance. Co-administration of milnacipran and levomepromazine increases the milnacipran plasma concentration because of a modification of the apparent total clearance of the drug. 

Psychiatric The incidence of suicide-related events in patients with schizophrenia or bipolar disorder taking aripiprazole has been studied using administrative data from three US sources [65 "]. Suicide attempts and death by suicide were assessed in patients aged at least 18 years. Among 20489 antipsychotic drug users (8985 patient-years), unadjusted suicide event rates per 1000 patient-years were 21 for aripiprazole 24 for olanzapine 32 for quetiapine 20 for risperidone and 49 for ziprasidone. Compared with current users of the other antipsychotic... 

Commercial drug products containing fine-particle active agents for intramuscular, intrasynovial, or intralesional administration are relatively common. These include products for the treatment of a variety of inflammatory conditions (methypred-nisolone acetate), bacterial infections (inipenem), acromegaly (octreotide acetate), endometriosis (leuprolide acetate), prostate cancer (triptorelin pamoate), and schizophrenia (risperidone). In some cases, these products are intended to provide therapeutic blood levels of the active agent for extended periods of time (the depot effect). Fine particles that are injected other than intravenously are not subject to the same particle size constraints as those that are injected directly into the bloodstream. 

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