What are the side effects of risperidone?

Risperidone Side Effects

Risperidone causes a distinct side effect profile dominated by extrapyramidal symptoms, metabolic disturbances, and hyperprolactinemia that requires systematic monitoring and risk mitigation strategies.

Neurological and Movement Side Effects

Extrapyramidal Symptoms (EPS)

• Risperidone produces more extrapyramidal symptoms than other atypical antipsychotics, making it the most likely drug in this class to cause movement disorders 1

• EPS risk increases significantly at doses exceeding 6 mg/24 hours 1

• Specific manifestations include:

  • Parkinsonism (14-28% in adults): muscle rigidity, bradykinesia, cogwheel rigidity, masked facies, and akinesia 1, 2
  • Akathisia (8-10% in adults): restlessness and inability to sit still 1, 2
  • Acute dystonia (3-6% in adults): involuntary motor tics or spasms involving face, extraocular muscles (oculogyric crisis), neck, back, and limb muscles—typically occurs after first doses or dose increases 1, 2
  • Tremor (2-11% in adults): parkinsonian rest tremor 1, 2

• Risperidone requires antiparkinsonian medication more frequently than clozapine (NNH 6), olanzapine (NNH 17), quetiapine (NNH 20), and ziprasidone 3

• Compared to typical antipsychotics, risperidone produces significantly fewer general movement disorders (NNT 3) and requires less antiparkinsonian medication (NNT 4) 4

Serious Neurological Complications

• Neuroleptic malignant syndrome has been documented in both adults and teenagers 1
• Tardive dyskinesia is potentially irreversible and reported in adults and teenagers 1
• Laryngeal dystonia is rare but life-threatening, presenting as choking sensation and difficulty breathing 1

Metabolic and Endocrine Side Effects

Weight Gain and Metabolic Syndrome

• Extreme weight gain is the most common significant problem with risperidone 1
• Pediatric patients gain an average of 2.7 kg over 8 weeks of treatment 5
• Adult patients experience significantly more weight gain than those on amisulpride (MD 0.99 kg), aripiprazole, or ziprasidone, but less than those on clozapine (MD -3.30 kg), olanzapine (MD -2.61 kg), quetiapine, or sertindole 3
• Increased appetite occurs in approximately 15% of patients 1, 5
• Risperidone is classified among second-generation antipsychotics with "more metabolic effects" on glucose metabolism, requiring systematic screening for dysglycemia 5

Lipid and Glucose Abnormalities

• Cholesterol increases more than with ziprasidone (MD 8.58 mg/dL) and aripiprazole (MD 22.30 mg/dL), but less than with quetiapine 3
• Fasting glucose screening is required at baseline, at 12-16 weeks, and then annually 5
• Metabolic syndrome associated with risperidone confers a 3- to 6-fold increased risk of diabetes 5

Hyperprolactinemia

• Risperidone increases prolactin levels more than all other atypical antipsychotics except amisulpride and sertindole 3
• Asymptomatic hyperprolactinemia is documented in pediatric patients 5
• Can result in amenorrhea and sexual dysfunction 6

Cardiovascular Side Effects

• Orthostatic hypotension is a common problem requiring monitoring, particularly in elderly and frail patients 1
• Can cause dizziness (6-16% in adults) and falls 1, 2
• QTc prolongation: risperidone causes 0-5 ms mean QT prolongation, significantly less than sertindole (MD -18.60 ms) 1, 3
• Palpitations occur in 2% of patients receiving adjunctive therapy 2

Gastrointestinal Side Effects

• Nausea occurs in 5-16% of adult patients 2
• Vomiting affects 10% of pediatric patients 2
• Diarrhea occurs in 3-8% of patients 2
• Salivary hypersecretion (drooling) affects 10% of pediatric patients and 2-3% of adults 5, 2
• Dyspepsia, stomach discomfort, and dry mouth are also reported 2

Central Nervous System Side Effects

• Sedation/somnolence is extremely common, occurring in 51-63% of pediatric patients and 10-56% of adults depending on dose 1, 5, 2
• Administering the dose in the evening can mitigate daytime drowsiness 5
• Headache affects 12-29% of patients 1
• Dizziness occurs in 6-16% of patients 2
• Lethargy affects 2% of patients 2
• Anxiety occurs in 3-16% of patients 2
• Insomnia affects 25-32% of patients 2
• Risperidone is less sedating than clozapine and quetiapine 3

Hematological Side Effects

• Leukocytopenia has been reported in teenage patients 1
• Agranulocytosis can occur with any antipsychotic agent, though primarily associated with clozapine 1
• Baseline and periodic monitoring should be considered in high-risk patients 1

Hepatic Side Effects

• Elevated hepatic transaminase levels are often transient and resolve with drug cessation 1
• Two cases of liver enzyme abnormalities and fatty infiltrates associated with obesity have been reported in adolescent males 1
• Mean liver enzyme levels increase significantly after both 1 and 6 months of treatment 5
• Baseline liver function tests with periodic monitoring during ongoing therapy are recommended 1, 5

Other Side Effects

• Nasal congestion/rhinitis occurs in 4-10% of patients (NNH 3 compared to typical antipsychotics) 2, 4
• Pharyngolaryngeal pain affects 3-10% of pediatric patients 2
• Rash occurs in 1-7% of patients 2
• Dry skin affects 1-3% of patients 2
• Epistaxis (nosebleeds) is reported in less than 2% of patients 2
• Urinary tract infection occurs in 2% of patients 2
• Back pain affects 4% of patients 2
• Arthralgia occurs in 2% of patients 2
• Dyspnea affects 1% of patients 2
• Cough occurs in 2% of patients 2
• Fatigue affects 2-30% of patients depending on indication 2
• Chest pain occurs in 2% of patients 2
• Blood creatine phosphokinase increase affects 1% of patients 2
• Heart rate increase occurs in less than 1% of patients 2
• Risperidone produces fewer seizures than clozapine (NNT 14) 3

Special Population Considerations

Pediatric Patients

• Higher rates of sedation, drooling, and weight gain compared to adults 1
• Extrapyramidal symptoms occur but may present differently than in adults 1
• Children with intellectual disability are more sensitive to risperidone-related adverse effects, supporting conservative starting doses and slower titration 5

Elderly Patients

• Use lowest effective doses (start 0.25-0.5 mg) and monitor closely for orthostatic hypotension 1
• Increased risk of falls due to dizziness and orthostatic hypotension 1

Critical Monitoring Requirements

• Weight, height, and BMI: at baseline, monthly for first 3 months, then quarterly 5
• Fasting blood glucose: at baseline, 3 months, then annually 5
• Fasting lipid panel: at baseline, 3 months, then annually 5
• Blood pressure: at baseline, 3 months, then annually 5
• Liver function tests: at baseline with periodic monitoring during maintenance 5
• Prolactin levels: periodic monitoring, particularly if clinical signs of hyperprolactinemia develop 5
• ECG monitoring: in patients with cardiac risk factors 1
• Complete blood count: at baseline in high-risk patients 1, 5
• Clinical assessment for EPS and tardive dyskinesia: at each visit 5