Risperidone adverse effects

These appear to be the only reports of an interaction between risperidone and protease inhibitors, and their general significanee is unclear. Until more is known it would be prudent to monitor patients taking risperidone who are given these protease inhibitors, particularly ritonavir, for risperidone adverse effects. 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

Case Example Because of a patient s partial response to 5 months of clozapine therapy at 600 mg/day, risperidone was added for augmentation (started with 0.5 mg b.i.d. and increased to 1 mg b.i.d. after 1 week). Before this addition, the clozapine plasma level was 344 ng/mL, but after 2 weeks of risperidone augmentation, the level was elevated to 598 ng/mL with no adverse effects and substantial clinical benefit. In another report, there was an increase in the steady-state plasma levels of clozapine (675 mg/day) and its active metabolite norclozapine after the addition of risperidone 2 mg/day in a patient treated for 2 years. Before the addition of risperidone, her clozapine and norclozapine levels were 829 and 1,384 ng/mL, respectively. Two days after risperidone was added, these levels rose to 980 and 1,800 ng/mL. Clozapine dosage was reduced to 500 mg/day, and after 5 days of combined treatment with 4 mg/day of risperidone, the clozapine and norclozapine levels were 110 and 760 ng/mL, respectively. Aside from some mild oculogyric crises, she had no symptoms of clozapine toxicity or clinical changes during the period of cross-tapering. In another case, risperidone was added to clozapine because the patient had relapsed after discontinuation of fluphenazine and had not responded to clozapine. The addition of risperidone resulted in an acute remission of psychosis ( 100). 

The introduction of clozapine, risperidone, quetiapine, and ziprazidone has had a dramatic impact on the decision-making process in choosing an antipsychotic. Thus, these agents both minimize neurological adverse effects and may qualitatively improve some psychotic symptoms to a greater degree than neuroleptics. 

Risperidone. Based on their review of the avaiiabie data on the efficacy and safety of risperidone, Umbricht and Kane ( 472) conciuded that the adverse effects most commoniy associated with risperidone treatment discontinuation in the United States and Canadian studies were dizziness (1-5%), nausea (1.2%), and agitation (1.0%). 

Nevertheless, this condition is responsive to treatment with dopamine-2 receptor antagonists. Hence, this condition is one of the clearest childhood indications for treatment with these medications. In theory, any dopamine-2 blocking receptor antagonist could be used. Haloperidoi has been the most extensively tested and used medication for this condition (167). The typical dose for children aged 3 to 12 years old is 0.2 mg/kg per day. More recently, in a double-blind study of 36 boys with Tourette s syndrome, risperidone was effective in reducing tics in 88% versus 60% for haloperidol (197), perhaps making risperidone a better option than a neuroleptic in terms of neurological adverse effects. 

Older typical antipsychotic drugs, as well as risperidone and paliperidone, produce adverse effects marked by elevations of prolactin, see Adverse... 

In 48 patients with schizophrenia taking clozapine, olanzapine, risperidone, or typical neuroleptic drugs, and 31 untreated healthy control subjects newer neuroleptic drugs, such as clozapine and olanzapine, compared with typical agents, were associated with adverse effects on blood glucose regulation (774). 

There were no significant adverse effects on growth or sexual maturation in a retrospective study based on a sample of 700 children aged 5-15 years who had been taking risperidone (0.02-0.06 mg/kg/day) for 11 or 12 months because of disruptive behavior disorders (1035). 

In CONCLUSION, the use of the "classical" neuroleptics, as exemplified by the phenothiazines, thioxanthines, butyrophenones and diphenylbutyl-piperidines, has been a landmark in the pharmacotherapy of schizophrenia and psychotic disorders. The efficacy of such drugs in the alleviation of the symptoms of schizophrenia is universally accepted. However, it is also evident that they have a spectrum of adverse effects that frequently renders their long-term use problematic. Side effects such as akathisia, Parkinsonism, tardive dyskinesia and the all too frequent changes in peripheral autonomic activity are largely predictable from the structure of the molecules and the basic animal pharmacology data. Such adverse effects, and the difficulties encountered when attempting to reduce their frequency and severity by concurrent medication, has stimulated the development of "atypical" neuroleptics such as clozapine and risperidone which, hopefully, will combine efficacy with a reduction in side effects. 

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. 

A 26-year-old woman with bipolar I disorder took lithium and valproate, and sometimes additional risperidone and lamotrigine. Both risperidone and lamo-trigine produced dermatological adverse effects. Her serum lithium concentration was 0.82 mmol/1. Topiramate 75 mg/day was added. A week later, she continued to show a mixed state with mostly manic features and a raised lithium concentration of 1.24 mmol/1. The lithium concentration continued to increase over the next 4 days to 1.97 mmol/1 even though the lithium dosage was reduced from 900 to 750 mg/day. Lithium was withdrawn and the lithium concentration fell. Lithium was then restarted at half the admission dose to achieve a blood concentration of 0.67 mmol/1. Subsequent increases in the dose of topiramate resulted in further increases in the lithium concentration. 

A 17-year-old man had taken risperidone for 2 years without adverse effects, but 12 weeks after lithium was added, he reported prolonged erections (lasting 1-3 hours) 2-5 times daily risperidone was tapered and withdrawn and the problem resolved (636). 

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