Risperidone other atypicals

Risperidone was launched in China in 1997. Following that, other atypical medication including olanzapine and quetiapine were introduced in the market in 1999 and 2000, respectively. These were followed by the development of generic arip-iprazole and ziprasadone in 2005 and 2006, respectively. Brand-name aripiprazole and ziprasadone will also be launched in 2007 in China. 

Table 11.4 shows that clozapine has approximately 10 times higher affinity for the D4 and 5-HT2A-receptors than the D2-receptor and shows a greater occupancy of the 5-HT2 than the D2-like receptors. The other atypical neuroleptic risperidone has a similar affinity for the two D2-like receptors but an affinity for the 5-HT2a-receptor that is just over 3 times lower than for the D2-receptor. Receptor occupancy in vivo shows a similar profile to clozapine. In contrast, haloperidol s affinity for the D4-receptor is just under 3 times lower and over 100 times lower for the 5-HT2a-receptor, with no binding to the latter in vivo. The fractional occupancy of striatal... 

Atypical Antipsychotics. The so-called atypical antipsychotics are not well studied in the treatment of ADHD. However, a few case reports have indicated that risperidone (Risperdal) may reduce the impulsivity and hyperactivity of ADHD. There is also preliminary evidence that risperidone may be effective in treating tics. Although the usefulness of risperidone and other atypical antipsychotics in treating ADHD needs more study, this may prove another viable treatment alternative for patients with ADHD and tics or agitation. 

Antipsychotics. Dopamine-blocking antipsychotics can be used to manage the agitation and psychotic symptoms that accompany delirium. Generally, low doses of high potency antipsychotics such as haloperidol have been most often used, though risperidone, ziprasidone, and other atypical antipsychotics are gaining increased acceptance. Because, as we mentioned earlier, some evidence indicates... 

Wilton LV, Heeley El, Pickering RM, et al. Comparative study of mortahty rates and cardiac dysrhythmias in post-marketing surveillance studies of sertindole and two other atypical antipsychotic drugs, risperidone and olanzapine. J Psychophar-macol 2001 15 120-6. 

The first atypical antipsychotic is clozapine. Several other atypical antipsychotics have been developed since clozapine was introduced. The first was risperidone, followed by olanzapine, quetiapine, and ziprasidone. 

Clozapine was the first atypical antipsychotic released in the United States. However, clozapine is associated with the risk of leukopenia and, potentially, lethal agranulocytosis. Because of these concerns, hematological monitoring during clozapine pharmacotherapy is required (Alphs and Anand, 1999). Due to these hematological risks, clozapine is indicated only for patients with treatment-resistant schizophrenia. The other atypical antipsychotics, risperidone, olanzapine, quetiapine, and ziprasidone, that are marketed in the United States can be used as first-line treatments for adults with schizophrenia. 

Risperidone, a novel benzisoxazole derivative, is an atypical antipsychotic medication that combines dopamine D2 receptor antagonism with potent 5-HT2 receptor antagonism. Risperidone has a higher affinity for dopamine D2 receptors than does clozapine. Risperidone also antagonizes dopamine Dj and D4 receptors, aj- and a2-adrenergic receptors, and histamine Hj receptors. Although the optimal dose of risperidone in North American trials was 6 mg/day, subsequent clinical experience has indicated that most patients do well at lower doses of 3-6 mg/day, and elderly patients may require doses as low as 0.5 mg/day. Unlike other atypical antipsychotics. 

The global efficacy of olanzapine was not substantially different from that of haloperidol in two of three comparative trials involving 2500 patients, according to a comprehensive review of the safety and efficacy of olanzapine in addition, the only relevant comparative trial failed to demonstrate superiority of olanzapine over risperidone (52). Olanzapine has fewer adverse neurological effects than haloperidol, but there is no evidence that it differs from other atypical neuroleptic drugs in this respect. 

Try one of the other atypical anti psych otics (risperidone, quetiapine, ziprasidone, aripiprazole, amisulpride)... 

Clozapine and olanzapine are the most likely of the atypical agents to cause anticholinergic (anti-muscarinic) effects. They are more likely than other atypicals to cause weight gain (glucose tolerance may be impaired and should be monitored in susceptible individuals) and are second only to quetiapine in their sedative effects. Sexual dysfunction and skin problems are rare with atypical antipsychotics. Risperidone and amisulpride are as likely as classical antipsychotics to raise prolactin concentrations and cause galactorrhoea. 

Since the release of clozapine, researchers have sought to develop an atypical antipsychotic without the side effects of clozapine (especially aplastic anemia). As of this writing, two other atypical agents have been released risperidone and olanzapine, and several others may soon be released, including sertindole and quetiapine. These agents vary somewhat in their pharmacological profile and, as a group, may... 

Other new atypical antipsychotics are not associated with an increased risk of agranulocytosis (unlike typical antipsychotics), are less likely to cause acute EPS, and probably are associated with a lesser risk of TD. Risperidone, another atypical agent, is not associated with an excessive risk of agranulocytosis but is highly... 

An example of recent work carried out by the DSRU includes the examination of mortality rates and cardiac arrhythmias between sertindole and two other atypical antipsychotics, olanzapine and risperidone. Tolterodine, an agent often used for urinary frequency and bladder instability, is the latest drug to be examined by the DSRU. ... 

Social workers need to be aware of the other atypical antipsychotic medications, such as risperidone, olanzipine and quentiapine. Risperidone (Risperdal) was introduced as the first official atypical antipsychotic medi-... 

RISPERDAL), for example, is a potent S-HT and receptor antagonist. Low doses of risperidone have been reported to attenuate negative symptoms of schizophrenia with a low incidence of extrapyramidal side effects. Extrapyramidal effects are commonly seen, however, with doses of risperidone in excess of 6 mg/day. Other atypical antipsychotic agents—quetiapine (seroquel) and olanzapine (zyprexa)—act on multiple receptors, but their antipsychotic properties are thought to be due to antagonism of DA and 5-HT. 

Several modem, better-tolerated antipsychotic agents (olanzapine, quetiapine, and risperidone) have recently received FDA approval for use in acute mania. There is also evidence of antimanic efficacy for aripiprazole and ziprasidone. Olanzapine is FDA-approved for its long-term effectiveness in bipolar disorder 1. Other atypical antipsychotic drugs are under investigation for long-term prophylactic treatment of bipolar disorder. 

Augmentation is called for when there is partial or non-response to the above approaches. Combinations of SSRIs with buspirone, clonazepam, clonidine, inositol, lithium, pindolol, olanzapine, risperidone, trazodone, tryptophan, and venlafaxine have been reported, with limited benefit. To date, only two augmenting agents have been found to be effective in double-blind studies risperidone and pindolol. Augmentation of SSRIs with clomipramine (or vice versa) is a common practice in non-responders however, this combination may lead to a substantial increase in the level of tricyclics in the blood and/or increase the risk of serotonin syndrome. Phenelzine may be helpful in symmetry-related or other atypical obsessions. Electroconvulsive therapy (ECT) should be reserved for severely depressed and suicidal OCD patients. Neurosurgery is the last resort current operations include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leucotomy. The outcome of such operations is questionable. 

Systematic reviews Amisulpride and other atypical antipsychotic drugs (olanzapine, risperidone, and ziprasidone) have been compared in people with schizophrenia and schizophrenia-like psychoses in an analysis of 10 short- to medium-term trials with 1549 participants [56 ]. The overall attrition rate was considerable (35%), with no significant difference between the groups. Amisulpride was as effective as olanzapine and risperidone and more effective than ziprasidone. Amisulpride caused less weight gain than risperidone and olanzapine. Olanzapine was associated with a greater rise in blood glucose. There were no differences in cardiac and extrapyrami-dal reactions. 

Restless leg syndrome has been associated with olanzapine in three cases, in which it started after the beginning of treatment with olanzapine and resolved after withdrawal all three patients were subsequently treated with other atypical antipsychotic drugs (risperidone, quetiapine, or aripiprazole) without recurrence [105 ]. 

Systematic reviews Ziprasidone has been compared with other atypical antipsychotic drugs in a systematic review [151 ]. The rate of premature study discontinuation was very high (59% n=3361). Ziprasidone was less efficacious than amisulpride, olanzapine, and risperidone, but based on limited data there were no significant differences in tolerability between ziprasidone and amisulpride or clozapine. Ziprasidone produced less weight gain than olanzapine (median difference, -3.8 95% Cl = -4.7, -3.0 ... 

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