Akathisia risperidone

In general, lower doses (e.g., risperidone 2 to 6 mg/day olanzapine 5 to 20 mg/day) are preferable, usually sufficient, and help avoid toxicity. At these doses, results suggest that olanzapine has a substantially lower propensity than neuroleptics to evoke EPS, and perhaps TD. Indeed, early clinical trials were unable to distinguish olanzapine from placebo for EPS or akathisia. Further, there is some indication that doses of risperidone 10 mg may produce less improvement and more side effects than doses in the 4-8 mg dose range. 

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. 

Extrapyramidal effects Parkinsonian symptoms, akathisia (motor restlessness), and tardive dyskinesia (inappropriate postures of the neck, trunk, and limbs) occur with chronic treatment. Blocking of dopamine receptors in the nigrostriatal pathway probably causes these unwanted parkinsonian symptoms. Clozapine and risperidone exhibit a low incidence of these symptoms. 

A single case report (Byerly et al., 1995) indicated that risperidone can produce severe akathisia, described as behavioral stimulation with anxiety and agitation. In a study of clozapine, 2 of 29 patients developed akathisia, one mild and the other moderate in intensity (Chengappa et al., 1994). 

Clozapine has also been compared with risperidone in 60 treatment-resistant patients with schizophrenia in India (16). There was clinical improvement (a more than 20% reduction from baseline PANSS scale scores) in 80% of the clozapine-treated patients and 67% of the risperidone-treated patients. The predominant adverse effects with clozapine (n = 30) were tachycardia (77%), hypersalivation (60%), sedation (60%), weight gain (43%), and constipation (30%) one patient had a seizure. The adverse effects of risperidone (n = 30) were constipation (50%), dry mouth (47%), weight gain (43%), akathisia (37%), insomnia (33%), tachycardia (30%), and impotence (27%). The final mean daily doses after 16 weeks of treatment were 343 mg for clozapine and 5.8 mg for risperidone. 

In an open comparison of risperidone and olanzapine (mean daily doses at follow-up 4.5 and 13.8 mg respectively) in 42 schizophrenic patients, there was a greater reduction in psychotic symptoms after 6 months of treatment with risperidone, although akathisia was more frequent (98). 

Akathisia has been reported in 16% of patients taking olanzapine (SEDA-21, 56). Three patients developed severe akathisia during treatment with olanzapine (20-25 mg/day) (87). In two, the akathisia resolved after withdrawal of olanzapine and in one of those olanzapine was well tolerated when reintroduced in combination with lorazepam. In the third patient, the akathisia was controlled by dosage reduction. A 33-year-old man with AIDS and a prior history of extrapyramidal symptoms with both typical antipsychotic drugs and risperidone developed dose-dependent akathisia with olanzapine 15-19 mg/day the akathisia responded to dosage reduction and beta-blockade (88). 

There was marked reduction in aggression in 14 of 26 subjects (10-18 years old) in an open study of risperidone (0.5 1 mg/day) for 2-12 months (17). Two subjects had marked weight gain (8 and 10 kg) in the first 8 weeks another participant who took lithium (1400 mg/day, serum concentration 0.9 mmol/1) presented with moderate akathisia and hand tremor in seven, tiredness and sedation occurred after week 8. 

In a 6-month multicenter study in 96 manic patients (mean age 41 years 50% women) who took risperidone monotherapy 4.2 mg/day, 16 withdrew from the study, in four cases because of adverse events akathisia, impotence, drowsiness, and weight gain (28). 

In a 1-year randomized comparison of risperidone (mean age 39 years 236 men n = 349) and conventional neuroleptic drugs (mean age 38 years 231 men n = 326), risperidone produced statistically superior scores on the Positive and Negative Syndrome Scale for Schizophrenia, Barnes Akathisia Scale, and 36-Item Short Form Health Survey scale however, there was no statistically significant difference in resource utilization between the two groups (29). This study, the Risperidone Outcome Study of Effectiveness (ROSE), was supported by Janssen, the market authorization holder of risperidone. 

A homozygous non-functional genotype, CYP2D6 4, was found in a 17-year-old patient with schizophrenia who developed severe akathisia, parkinsonism, and drowsiness after taking risperidone 6 mg/day for 3 months he had high plasma concentrations of risperidone and an active metabolite (210). 

Finally, of 192 patients who had remained symptomatically stable for at least 1 month with another major second-generation antipsychotic drug, olanzapine (mean age 38 years 63% men), 70% completed a 6-month study with injectable risperidone treatment-related adverse events were reported by 121 patients (63%), mostly anxiety (12%), exacerbation of disease (10%), insomnia (9%), depression (6%), and akathisia (5%) (231). 

The optimal dose of risperidone in first-episode schizophrenia has been studied in 17 drug-naive patients (12 women, 5 men mean age 29 years) (234). The mean optimal dosage of risperidone was 2.70 mg/day. All the patients reached the optimal dose before developing extrapyramidal adverse effects four developed parkinsonism and one developed akathisia at a mean dosage of 5.20 mg/day. In contrast, acute exacerbations of schizophrenia may require a higher dose. 

Cocaine has been associated with movement disorders, such as acute dystonias, choreoathetosis, and akathisia. Chronic pancerebellar dysfunction occurred in a cocaine user with schizophrenia treated with risperidone (129). 

A pharmacokinetic interaction of risperidone with fluoxetine has been reported (SEDA-22, 71). When 10 schizophrenic patients stabilized on risperidone 4-6 mg/day took fluoxetine 20 mg/day for concomitant depression the mean plasma risperidone concentration increased from 12 to 56 ng/ml at week 4 the concentration of 9-hydroxyrisperidone was not significantly affected (169). One patient dropped out after 1 week because of akathisia associated with a markedly increased plasma risperidone concentration. 

Olanzapine, quetiapine, and risperidone are preferred alternative atypicals aripiprazole and ziprasidone are newer agents and may initially cause akathisia-like reactions clozapine is usually reserved for treatment-resistant mania or mixed states. 

In a few cases, marked extrapyramidal side-effects (akathisia, dystonia, and parkinsonism) have been reported with flupbenazine, perphenazine, sulpiride, and thiothixene when fluoxetine is added to the regimen. The mechanism is speculated to be the result of fluoxetine-induced further suppression of dopaminergic activity in the nigrostriatal pathways (serotonergic stimulation leads to decreased dopamine release), in addition to increases in their plasma concentration. Fluoxetine has been shown to increase haloperidol serum levels by about 20%, presumably via inhibition of cytochrome P450 enzymes. Fluoxetine can increase the risk of seizure induction when added to clozapine due to an increase in clozapine serum levels, or by additive effects. Concomitant treatment with fluoxetine and risperidone is associated with a mean 4-fold increase in the plasma concentration of risperidone. ... 

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