Sedation risperidone

In another study, 118 children with IQs ranging from 35 to 84 who demonstrated conduct disorder were randomized to risperidone (at a mean dose of 1.23 mg/day) versus placebo in a double-blind design (96). In comparison with placebo, risperidone produced a statistically significant reduction in insecure/anxious behavior, hyperactivity, self-injurious/stereotyped behavior, irritability, and aggressive/destructive behavior, as well as an increase in adaptive social behavior. The latter is important because it shows that the changes are not due to sedation, although more somnolence was apparent with risperidone. 

In the development of new antipsychotics, cQT intervals are routinely evaluated but it is currently unclear how predictive these are of clinically significant cardiotoxicity or sudden death. For this reason, the heart rate variability (HRV) index has been developed. It has been shown that the HRV decreases after TCAs and clozapine. In a comparison of the acute effects of olanzapine, risperidone and thioridazine in healthy male volunteers, olanzapine was shown to increase, thioridazine to decrease while risperidone was without effect on the HRV. A decrease in the HRV is an established predictor of poor cardiac outcome. The cardiac changes were unrelated to the degree of sedation caused by the drugs. 

Risperidone Minimal sedation, low potential for extrapyramidal effects. ... 

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 8-week study, pre-school-age children with bipolar disorder (aged 4-6 years) took either olanzapine (n = 15 mean age 5.0 years 10 boys mean dose 6.3 mg/day) or risperidone (n = 16 mean age 5.3 years 12 boys mean dose 1.4 mg/day) (59). There were significantly more dropouts with olanzapine (6 versus 1), including one patient who withdrew because of adverse events (increased appetite and hand tremor). The main adverse events, found with both treatments, were significant increases in prolactin concentrations and weight gain. With both treatments, increased appetite, flu-like symptoms, headaches, and sedation were the most commonly reported adverse effects. 

Patients with bipolar disorders may benefit from risperidone. This has been observed in an open trial of ten patients with rapid cycling bipolar disorder who were refractory to lithium carbonate, carbamazepine, and valproate eight improved after 6 months of treatment. One patient dropped out through non-adherence to therapy and one because of adverse effects (agitation, anxiety, insomnia, and headache) (5). There was a similar beneficial effect in eight adults with moderate to profound mental retardation (6). Risperidone was associated with a significant reduction in aggression and self-injurious behavior, whereas adverse effects were primarily those of sedation and restlessness. 

The medical records of 151 hospitalized elderly psychiatric patients (mean age 71 years) have been analysed (8). Of 114 patients treated with risperidone (mean duration of treatment 17 days mean dose 3 mg/day), 78% responded. Adverse events were reported in 20 patients, including new-onset extrapyramidal effects in four tremor in four sedation in three hypotension in three diarrhea in two tardive dyskinesia in two and chest pain, anxiety, restlessness, itching, insomnia, and falls in one each. 

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 double-blind, placebo-controlled study of the addition of low-dose risperidone (mean dosage 2.2 mg/day) to a 5-HT re-uptake inhibitor in refractory obsessive-compulsive disorder in 70 adults, 18 of 20 risperidone-treated patients had at least one adverse effect (37). The adverse effects in both groups included sedation (n = 17 for risperidone, n = 8 for placebo), increased appetite (6 and 3), restlessness (6 and 6), and dry mouth (5 and 5). 

Adults with autistic disorder (n = 17) or pervasive developmental disorder not otherwise specified (n = 14) participated in a randomized, 12-week, double-blind, placebo-controlled trial of risperidone (41). Among those who completed the study, risperidone (n = 14) was superior to placebo (n = 16) in reducing the symptoms of autism, and the most prominent adverse effect was mild transient sedation during the initial phase of drug administration. Abnormal gait was reported in one patient taking risperidone. 

In a two-phase placebo-controlled study with an initial sample of 45 patients, 39 of whom completed the study, the addition of low doses of risperidone (0.5 mg/day) appeared to improve symptoms in patients with obsessive-compulsive disorder taking fluvoxamine monotherapy (51). The main adverse events included transient sedation and mildly increased appetite. 

Adverse effects leading to dosage reduction or discontinuation were also observed in a retrospective study in 57 patients mean age 84 (range 66-97) years, who took risperidone (doses 0.5-4 mg/day) for more than 1 year (average 2 years) for dementia-related behavioral disturbances (215). Adverse effects included hypotension (n = 4), agitation (n = 6), and sedation (n = 5), and six patients developed a new movement disorder. 

An example of SPE-LC-MS is the determination of Ro 48-6791, a short-acting agent for conscious sedation, and its major metabolite in human plasma [108]. In this particular case, the rationale for the use of the precolumn was in enlarging the permissible injeetion volume, beeause a 300-pm-ID microeapillaiy packed column was used in LC. The determination of risperidone and 9-hydroxyrisperidone in plasma and saliva from adult and pediatrie patients using SPE-LC-MS was discussed inCh. 11.4.2 [45]. 

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