Risperidone side effects
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
List of side effects
Overview
Associated with discontinuation of treatment
Commonly observed in controlled clinical trials
Incidence of 1% or more (schizophrenia)
Overview
The following findings are based on the short-term, placebo-controlled, North American, premarketing trials for schizophrenia and acute bipolar mania, and are followed by a description of adverse events and other safety measures in short-term, placebo-controlled trials in pediatric patients treated for irritability associated with autistic disorder. In patients with Bipolar I Disorder, treatment-emergent adverse events are presented separately for risperidone as monotherapy and as adjunctive therapy to mood stabilizers.
Certain portions of the discussion below relating to objective or numeric safety parameters, namely dose-dependent adverse events, vital sign changes, weight gain, laboratory changes, and ECG changes are derived from studies in patients with schizophrenia. However, this information is also generally applicable to bipolar mania and pediatric patients with autistic disorder. Return to top
Associated with discontinuation of treatment
Schizophrenia (discontinuation)
Approximately 9% (244/2607) of Risperdal® (risperidone)-treated patients in Phase 2 and 3 studies discontinued treatment due to an adverse event, compared with about 7% on placebo and 10% on active control drugs. The more common events (≥0.3%) associated with discontinuation and considered to be possibly or probably drug-related included: extrapyramidal symptoms, dizziness, hyperkinesia, somnolence, nausea.
Suicide attempt was associated with discontinuation in 1.2% of Risperdal®-treated patients compared to 0.6% of placebo patients, but, given the almost 40-fold greater exposure time in Risperdal® compared to placebo patients, it is unlikely that suicide attempt is a Risperdal®-related adverse event. Discontinuation for extrapyramidal symptoms was 0% in placebo patients, but 3.8% in active-control patients in the Phase 2 and 3 trials. Return to top
Bipolar mania (discontinuation)
In the US placebo-controlled trial with risperidone as monotherapy, approximately 8% (10/134) of Risperdal®-treated patients discontinued treatment due to an adverse event, compared with approximately 6% (7/125) of placebo-treated patients. The adverse events associated with discontinuation and considered to be possibly, probably, or very likely drug-related included paroniria, somnolence, dizziness, extrapyramidal disorder, and muscle contractions involuntary. Each of these events occurred in one Risperdal®-treated patient (0.7%) and in no placebo-treated patients (0%).
In the US placebo-controlled trial with risperidone as adjunctive therapy to mood stabilizers, there was no overall difference in the incidence of discontinuation due to adverse events (4% for Risperdal® vs. 4% for placebo).Return to top
Commonly observed in controlled clinical trials
Schizophrenia (common)
In two 6- to 8-week placebo-controlled trials, spontaneously-reported, treatment-emergent adverse events with an incidence of 5% or greater in at least one of the Risperdal® groups and at least twice that of placebo were anxiety, somnolence, extrapyramidal symptoms, dizziness, constipation, nausea, dyspepsia, rhinitis, rash, and tachycardia.
Adverse events were also elicited in one of these two trials (i.e., in the fixed-dose trial comparing Risperdal® at doses of 2, 6, 10, and 16 mg/day with placebo) utilizing a checklist for detecting adverse events, a method that is more sensitive than spontaneous reporting. By this method, the following additional common and drug-related adverse events occurred at an incidence of at least 5% and twice the rate of placebo: increased dream activity, increased duration of sleep, accommodation disturbances, reduced salivation, micturition disturbances, diarrhea, weight gain, menorrhagia, diminished sexual desire, erectile dysfunction, ejaculatory dysfunction, and orgastic dysfunction.
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Bipolar mania (common)
In the US placebo-controlled trial with risperidone as monotherapy, the most commonly observed adverse events associated with the use of Risperdal® (incidence of 5% or greater and at least twice that of placebo) were somnolence, dystonia, akathisia, dyspepsia, nausea, parkinsonism, vision abnormal, and saliva increased. In the US placebo-controlled trial with risperidone as adjunctive therapy to mood stabilizers, the most commonly observed adverse events associated with the use of Risperdal® were somnolence, dizziness, parkinsonism, saliva increased, akathisia, abdominal pain, and urinary incontinence. Return to top
Incidence of 1% or more (schizophrenia)
The list that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent among Risperdal®-treated patients treated at doses of ≤10 mg/day than among placebo-treated patients in the pooled results of two 6- to 8-week controlled trials. Patients received Risperdal® doses of 2, 6, 10, or 16 mg/day in the dose comparison trial, or up to a maximum dose of 10 mg/day in the titration study. This table shows the percentage of patients in each dose group (≤10 mg/day or 16 mg/day) who spontaneously reported at least one episode of an event at some time during their treatment. Patients given doses of 2, 6, or 10 mg did not differ materially in these rates. Reported adverse events were classified using the World Health Organization preferred terms.
The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in this clinical trial. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the side effect incidence rate in the population studied.
- Psychiatric: insomnia, agitation, anxiety, somnolence, aggrassive reaction
- Central/peripheral nervous system: extrapyramidal symptoms, headache, dizziness
- Gastrointestinal: constipation, nausea, dyspepsia, vomiting, abdominal pain, saliva increased, toothache
- Respiratory system: rhinitis, coughing, sinusitis, pharyngitis, dyspnea
- Body as a whole: back pain, chest pain, fever
- Dermatological: rash, dry skin, seborrhea
- Infections: upper respiratory
- Visual: abnormal vision
- Musculo-skeletal: arthralgia
- Cardiovascular: tachycardia
Adapted from the FDA Package Insert.