Risperidone long-term effects

Troost PW, Lahuis BE, Steenhuis MP, Ketelaars CE, Buitelaar JK, van Engeland H, Scahill L, Minderaa RB, Hoekstra PJ. Long-term effects of risperidone in children with autism spectrum disorders a placebo discontinuation study. J Am Acad Child Adolesc Psychiatry 2005 44 1137-44. 

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. 

Kim EY, Chang SM, Shim JC, Joo EJ, Kim JJ, Kim YS, et al. Long-term effectiveness of flexibly dosed paliperidone extended-release comparison among patients with schizophrenia switching from risperidone and other antipsychotic agents. Curr Med Res Opin 2013 29(10) 1231-40. 

Ari pi prazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). 

In reality, risperidone acts as an atypical antipsychotic at doses up to 4-6mg/day. At higher doses, risperidone begins to act more like a typical antipsychotic, and EPS can become a problem. The dose at which this occurs for individual patients is quite variable. In elderly patients, even low doses can cause EPS. Whether this risk for EPS translates into a risk for TD after long-term use remains unknown. There is now considerable evidence that risperidone is also effective in treating mania and in augmenting antidepressants in particularly low doses. 

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. 

Clozapine, risperidone, olanzapine, quetiapine, and ziprasidone have all been approved for the treatment of schizophrenia. Data from long-term open evaluations of clozapine demonstrate that improvement is maintained over time, even when the dose is reduced. Further, patients did not develop tolerance to its antipsychotic effect. Naturalistic reports indicate that an adequate trial for acute response in some patients may be at least 6 months. Further, a small number (8 of 14) of previously refractory patients were successfully maintained on clozapine for up to 2 years ( 215). 

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. 

Fig. 9. Effects of 3 neuroleptics (tiapride, haloperidol and risperidone) on escape latencies during the first trial of the same Morris maze task on 3 consecutive days. Note the clear decrease in escape latencies in the vehicle control group from day to day (long-term memory). Tiapride has no effect on the decrease in the first trial escape latency from day to day (absence of effect on long-term memory), whereas haloperidol clearly attenuates this decrease with a similar tendency for risperidone (perturbing effect on long-term memory).

The same group of antipsychotic drugs have been evaluated for their effects on working memory (276,277) in a visual spatial version of the delayed non-matching to position paradigm (278,279). Haloperidol and risperidone exhibit marked inhibitory effects in low doses, whereas considerably higher doses of clozapine, olanzapine, and ziprasidone are required to produce similar effects (276). Sertindole and quetiapine are inactive at the doses tested (276). Long-term treatment reveals a continued memory impairment of memory by haloperidol, the development of tolerance to the effects of clozapine on memory, and continued lack of impairment by sertindole (277). 

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