What are the side effects of risperidone?

Side Effects of Risperidone

Risperidone causes a range of common and serious side effects, with weight gain, sedation, and extrapyramidal symptoms being the most clinically significant, and notably, risperidone produces more extrapyramidal symptoms than other atypical antipsychotics. 1, 2

Most Common Side Effects

Metabolic Effects

• Weight gain and increased appetite occur in 36-52% of pediatric patients and 8-82% across all age groups, representing the most common significant problem with risperidone 3, 4
• Weight gain is dose-dependent: each 1 mg increase in daily dose causes 0.16% weight increase at 1 month and up to 0.29% at 3 months 5
• Each additional milligram increases risk of ≥5% weight gain (OR 1.18) after just 1 month, which strongly predicts long-term weight gain 5
• Total cholesterol increases by 0.05 mmol/L and LDL cholesterol by 0.04 mmol/L per milligram increase after 1 year of treatment 5

Neurological Effects

• Somnolence/drowsiness occurs in 51-63% of pediatric patients 6, 3, 4
• Fatigue affects 31% of pediatric patients 4
• Drooling/hypersalivation occurs in 12% of pediatric patients 4
• Headache affects 12-29% of patients 6, 4

Other Common Effects

• Fever (pyrexia) occurs in 16% of pediatric patients 4
• Enuresis (bedwetting) affects 16% of pediatric patients 4
• Nasopharyngitis and upper respiratory infections occur in 8-19% 4
• Nausea, vomiting, and dyspepsia occur in 15-20% 6, 4

Serious Extrapyramidal Side Effects (EPS)

Risk Profile

• Risperidone is the most likely among atypical antipsychotics to produce extrapyramidal symptoms 1, 2
• EPS risk is dose-dependent: incidence increases from 7% at 1 mg/day to 35% at 16 mg/day in adults 4
• Risk substantially increases at doses >6 mg/24 hours 2

Specific Movement Disorders

• Parkinsonism: muscle rigidity, bradykinesia, cogwheel rigidity, masked facies, and akinesia occur in 8% of pediatric patients 2, 4
• Acute dystonia: involuntary motor tics or spasms involving face, neck, back, and limbs—typically occurs after first few doses or dose increases 2
• Akathisia: restlessness and inability to sit still, with incidence up to 2% at higher doses 2, 4
• Tremor: Parkinsonian rest tremor 2
• Tardive dyskinesia: potentially irreversible movement disorder reported in both adults and teenagers 1, 2
• Neuroleptic malignant syndrome: rare but life-threatening, documented in adults and teenagers 1, 2
• Laryngeal dystonia: rare but life-threatening, presents as choking sensation and difficulty breathing 2

Endocrine Effects

• Asymptomatic prolactin elevation is common and more pronounced than with other atypical antipsychotics 1, 3
• Can result in amenorrhea, menstrual irregularities, and sexual dysfunction 4, 7
• Gynecomastia and galactorrhea may occur 4

Cardiovascular Effects

• Orthostatic hypotension is a common problem requiring monitoring, particularly in elderly and frail patients 2
• Can cause dizziness and falls 2
• QTc prolongation: causes 0-5 ms mean QT prolongation, less than many other antipsychotics 2

Rare but Serious Effects

Hematological

• Leukocytopenia: case reports in teenage patients 2
• Agranulocytosis can occur with any antipsychotic, though primarily associated with clozapine 2

Hepatic

• Elevated hepatic transaminase levels: often transient and resolve with drug cessation 2
• Case reports of liver enzyme abnormalities and fatty infiltrates associated with obesity in adolescent males 2

Other Rare Effects

• Peripheral edema: rare but can affect patient compliance and quality of life 8
• Hyperglycemia requires monitoring 9

Age-Specific Considerations

Pediatric Patients

• Higher rates of sedation, drooling, and weight gain compared to adults 2
• Adolescents show dose-dependent weight gain up to 1.63% per mg increase at 3 months 5

Elderly Patients (≥65 years)

• More sensitive to orthostatic hypotension—require lower starting doses (0.25-0.5 mg) 2
• Show dose-dependent weight gain up to 1.58% per mg increase 5

Discontinuation Rates

• Approximately 7% of adult patients discontinue due to adverse reactions in schizophrenia trials 4
• 12% of pediatric patients with bipolar mania discontinue due to adverse reactions 4
• Most common reasons for discontinuation: dizziness, somnolence, sedation, nausea, and extrapyramidal symptoms 4

Monitoring Requirements

• Baseline and periodic monitoring should include weight, height, metabolic parameters (glucose, lipids), and prolactin levels 3, 2
• Regular neurological examination for extrapyramidal symptoms 1
• ECG monitoring in patients with cardiac risk factors 2
• Baseline liver function tests with periodic monitoring during ongoing therapy 2