Somnolence risperidone

Quetiapine IR at maximal dose (750 mg per day) was compared to oral risperidone in a 6-week, multicenter, randomised, rater single-blind study in Chinese patients with schizophrenia Extrapyramidal symptoms, prolactin levels and upper respiratory infection were significantly lower for quetiapine than for risperidone. Dizziness was significantly higher with quetiapine than with risperidone. Somnolence was greater with quetiapine. 

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 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. 

Risperidone has also been used in combination with topiramate in a Spanish multicenter study in 58 patients (28 men and 30 women mean age 41 years) with bipolar I disorder, with manic but not mixed episodes (20). Risperidone (mean dose 2.7 mg/day) and topiramate (mean dose 236 mg/day) were started with a maximum 48-hour time difference risperidone was used for acute manic symptoms and topiramate for longer-term stabilization and prevention of relapse. The incidence of any adverse event was 64%, mostly somnolence, paresthesia, dizziness, tremor, weight loss (n = 27 mean change -1.1 kg), extrapyramidal disorders, gastrointestinal effects, and cognitive disturbances. One patient developed tardive dyskinesia during the study and there were five dropouts because of adverse effects adverse effects that required withdrawal of risperidone but not topiramate were amenorrhea (n = 3) and sexual dysfunction (n = 1). 

In a two-phase long-term multicenter study in 74 patients (mean age 30 years 56 men), the starting dose of risperidone was 1 mg/day, increased to 2 mg after 3 days and adjusted to 8 mg/day maximum treatment duration was 2 weeks for phase 1 (mean dose at the end 3.8 mg/day) and 1 year for phase 2 (mean dose at the end 3.5 mg/day) (26). Of 12 patients who did not complete phase 1, two had adverse events (agitation, somnolence, and self-harm) there were nine dropouts during phase 2, but none was apparently due to adverse events. 

In a multicenter, randomized, double-blind, 12-week trial in Australia and New Zealand, 384 patients with dementia, mainly Alzheimer s disease, were initially enrolled and received at least one dose of risperidone (n = 167 71% women mean age 83 years modal dose 0.99 mg/day) or placebo (n = 170 72% women mean age 83 years) (47). Clinical improvement in aggression and psychotic symptoms was evidenced by means of specific scales 45 subjects taking risperidone and 56 taking placebo did not complete the trial, mainly because of insufficient responses and adverse effects. In the whole sample there was a high prevalence and variety of adverse events (94% of those taking risperidone and 92% of those taking placebo), mainly injuries, falls, somnolence, and urinary tract infections however, only the last two were more common in those taking risperidone than in those... 

Possible interactions between donepezil and risperidone, which are both metabolized by CYP2D6 and CYP3A4, have been studied (SEDA-26,65) (247). Of 24 healthy men (mean age 40 years) were assigned to risperidone 1 mg/day, donepezil 5 mg/day, or both, 20 reported at least one adverse event, mostly headache, nervousness, or somnolence. However, measures of pharmacokinetics showed no interaction. 

An open comparison of donepezil and risperidone, alone or in combination, in 24 healthy men showed no significant pharmacokinetic differences (88). Adverse events such as headache, nervousness, and somnolence were minor and comparable in all groups. These results suggest that no clinically significant interactions occur between risperidone and donepezil at steady state. However, whether these conclusions can be extrapolated to the elderly patients with dementia, who may eliminate both donepezil and risperidone slowly, is uncertain. 

Risperidone was also effective and well tolerated in 118 children aged 5-12 years with subaverage intelligence and severely disruptive behavior in a 6-week, multicenter, double-blind, randomized trial (7). Risperidone produced significantly greater improvement than placebo on the conduct problem subscale of the Nisonger Child Behavior Rating Form from week 1 (respective reductions in score of 15 and 6). The most common adverse effects of risperidone (mean dose at end-point 1.16 mg/day) were headache and somnolence the extrapyramidal symptom profile of... 

The safety, tolerability, and efficacy of risperidone have been assessed in 103 patients with schizophrenia (52 men and 51 women) aged 65 years or older in an open, multicenter, 12-week study (141). The mean risperidone dose at end-point was 2.4 mg/day. Adverse events occurred in 91 patients and included dizziness (n = 23), insomnia (n = 17), agitation (n = 15), somnolence (n = 15), injury (n = 12), constipation (n = 11), and extrapyramidal disorders (n = 10) 11 patients withdrew because of adverse events. Among the 91 patients with normal baseline QTc intervals (below 450 ms), 9 had a prolonged QTc interval during the study (range 450-516 ms). 

Until the advent of the atypical antipsychotics, conventional agents were widely used, although available placebo-controlled studies suggested that they were moderately effective at best. More recently, risperidone has been shown to have modest effects in patients with psychotic symptoms or behavioral disturbances associated with dementia. " It is recommended to begin with 0.25 mg daily and to titrate in 0.25- to 0.5-mg increments to 1 mg daily, which is usually considered the optimal dose. If response is inadequate, further titrating to a maximum of 2 mg daily may be necessary if the patient is tolerating the medication however, side effects, particularly extrapyramidal effects, somnolence, and orthostasis, increase with increased dose. 

In a review of the use of risperidone in autistic disorder in children and adolescents it was stressed that somnolence, increased appetite, increased prolactin concentrations, and fatigue were the most common adverse events [117 ]. 

In a retrospective study of male delinquents, mean age 16 years, with childhood onset and persistent conduct disorder treated either with psychosocial treatment and risperidone (mean dose 2.5 mg/day n = 60) or cognitive-behavioral treatment alone n = 69), the most common adverse events in the patients taking risperidone were somnolence (26%), weight gain (18%), increased appetite (17%), and constipation (14%) mean body weight increased by 6.8 kg during a mean time of 9 months [119. ... 

Observational studies Numerous open studies of ziprasidone promoted by Pfeer, the marketing authorization holder, have previously been published [SEDA-32, 111] and further studies, similarly promoted, have emerged. Of 185 subjects who were switched from olanzapine or risperidone to ziprasidone, 72 completed a 1-year extension study [136 ]. The most common adverse effects were insomnia (23%) and somnolence (11%) no patient had a corrected QT interval over 500 ms at any time during the study. 

Nervous system A study comparing somnolence with asenapine, olanzapine, risperidone and haloperidol relative to placebo evaluated 10 clinical trials of patients with schizophrenia or bipolar disorder [36 -]. The duration and incidence of somnolence was greatest for asenapine and olanzapine (maximal for olanzapine) and with shorter time to onset than the other antipsychotics and placebo patients with bipolar disorder were the most sensitive. 

Four SGA long-acting injections are currently available risperidone microspheres, olanzapine pamoate, paliperidone palmitate and aripiprazole extended-release injection. The extended-release characteristics are achieved differently with each drug. A case analysis of clinical frials with olanzapine pamoate (2000-2008) reported an occurrence of postinjection delirium/sedation syndrome in approximately 0.07% of injections or 1.4% of patients [78 ]. A review of the published literature and clinical trial databases for olanzapine pamoate, risperidone microspheres and paliperidone palmitate found only one other case of postinjection delirium/sedation syndrome occurring in a patienf on placebo in a paliperidone palmitate trial. In four randomised, double-blind, placebo-controlled trials of paliperidone palmitate, the most common treatment-emergent adverse event was somnolence/sedation overall treatment discontinuation rates due to adverse events were similar to placebo. 

Observational Studies In a 12-week study of children and adolescents with autism spectrum disorders switched from risperidone to aripiprazole, mild somnolence was observed only in one subject and there were no significant changes in vital signs, weight or ECG while serum prolactin levels decreased significantly [90 ]. 

In a 20-week study of bipolar manic patients treated with oral risperidone, the most common adverse events included gastrointestinal disturbances (nausea), weight gain, headaches, somnolence and extrapyramidal symptoms (tremor, unsteady gait, muscle stiffness) 23% of patients gained >7% weight [242 ]. 

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