Extrapyramidal symptoms risperidone

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

The four drugs were administered by psychiatrists blinded to treatment group assignment of patients. The 14-week study consisted of an 8-week dose escalation and fixed dose and a 6-week variable-dose period. The mean dose levels (mg/day) of the four compounds after the first 8 weeks were 452 for clozapine. 20.2 for olanzapine. 8.3 for risperidone and 19.6 for haloperidol. Patients on haloperidol received prophylactic anticholinergic medication to prevent extrapyramidal symptoms, and a few other drugs were permitted to treat agitation and insomnia. 

Kapur S, Remington G, Zipursky RB, et al. The D 2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms a PET study. Life Sci 1995 57 103-107. 

In an open, 30-day trial, the pharmacokinetics, safety, and tolerability of a combination of risperidone 4 or 6 mg/ day with fluoxetine 20 mg/day were evaluated in 11 psychotic inpatients (52). CYP2D6 genotyping showed that three were poor metabolizers and eight were extensive metabolizers. The mean AUC of risperidone increased from 83 and 398 h.ng/ml to 341 and 514 h.ng/ml when risperidone was co-administered with fluoxetine in extensive and poor metabolizers respectively. However, despite this pharmacokinetic interaction, the severity and incidence of extrapyramidal symptoms and adverse events did not increase significantly when fluoxetine was added 10 of the 11 patients improved clinically. 

Extrapyramidal symptoms have been identified at much higher rates in psychotic youths than in comparable adult populations (194). Subjects who selected because of prominent positive psychotic symptoms were randomly assigned to double-blind, parallel treatment with risperidone (mean age 15 years mean dose at termination 4 mg n = 19), olanzapine (mean age, 14.6 years mean dose at termination, 12.3 mg n = 16) or haloperidol (mean age 15 years mean dose at termination 5 mg n = 15) for 8 weeks in all, 88% of those who took olanzapine, 74% of those who took risperidone, and 53% of those who took... 

Heck AH, Haffmans PM, de Groot IW, Hoencamp E. Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms a double-blind, multi-center trial. Schizophr Res 2000 46(2-3) 97-105. 

A 28-year-old woman simultaneously developed four types of tardive extrapyramidal symptoms (dystonia, dyskinesia, choreoathetotic movements, and myoclonus) while taking haloperidol the symptoms were subsequently relieved by the use of low-dose risperidone (3 mg/day) (19). 

Suenaga T, Tawara Y, Goto S, Kouhata SI, Kagaya A, Horiguchi J, Yamanaka Y, Yamawaki S. Risperidone treatment of neuroleptic-induced tardive extrapyramidal symptoms. Int J Psychiatry Chn Pract 2000 4 241-3. 

In a retrospective study in 499 in-patients with schizophrenia or schizoaffective disorder (39) 259 subjects were taking olanzapine and 240 risperidone. Treatment was considered effective in most cases (74% with olanzapine and 78% with risperidone). There were adverse effects in 19% of the patients taking olanzapine and 22% of those taking risperidone they were mainly somnolence (n = 15 and n = 17 respectively) and extrapyramidal symptoms (n = 9 and n = 6 respectively) there were also three cases of weight gain with olanzapine. 

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). 

Several symptoms of dementia can be improved by risperidone. In 18 patients with Alzheimer s disease (no sex or age data reported), delusions of theft, hallucinations, and agitation/aggression improved significantly after 12 weeks of treatment (22). The modal optimal dosage was 1 mg/day, the same already suggested for this pathology (SEDA-26, 64). There were mild extrapyramidal symptoms at some point during the trial in one patient. 

Similarly, risperidone caused extrapyramidal symptoms in fewer patients (24%) than haloperidol did (43%) in a two-phase study in patients with acute bipolar mania (phase I, 3 weeks, patients receiving either risperidone 1-6 mg/day, haloperidol 2-12 mg/day, or placebo (32). Plasma prolactin concentration was higher with risperidone (no data provided) prolactin-related adverse events included non-puerperal lactation, breast pain, dysmenorrhea, and reduced libido or sexual dysfunction these effects occurred in six patients on risperidone (4%) and in two on haloperidol (1.3%). 

In a 6-week open study of risperidone (mean dosage 4.7 mg/day) in combination with mood-stabilizing treatments (usually lithium, carbamazepine, or valproate) for the treatment of schizoaffective disorder in 102 patients, 95 of whom completed the trial, at week 4 most patients had improved symptom severity and 9.3% were completely symptom-free (35). There were no statistically significant differences between baseline and week 4 in the severity of extrapyramidal symptoms, as measured by the UKU Side-Effect Rating Scale subscale for neurological adverse effects other adverse effects included depressive symptoms (n = 13), exacerbation of mania ( n = 5), drowsiness (n = 3), and impotence (n = 2). 

In a 9-week open study of risperidone for agitated behavior in 15 patients with dementia (modal dose 0.5 mg/day), extrapyramidal symptoms developed at some point during the trial in 8 patients, and cognitive skills were impaired in 3 patients (70). Similarly, in 22 patients with dementia and behavioral disturbances, treated with risperidone 1.5 mg/ day (range 0.5 mg qds to 3 mg bd), 50% had significant improvement, but 50% had some extrapyramidal symptoms (71). A further case of a severe extrapyramidal reaction in an old patient with dementia further illustrated these susceptibility factors (72). 

Extrapyramidal symptoms have been reported within 24 hours of an injection of depot risperidone in patients with schizophrenia (73). 

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