What are the side effects of risperidone?

Risperidone Side Effects

Risperidone causes somnolence (51%), headache (29%), vomiting (20%), weight gain (15%), and asymptomatic hyperprolactinemia as its most common adverse effects in pediatric patients, with extrapyramidal symptoms occurring in a dose-dependent manner. 1

Most Common Side Effects by Population

Pediatric Patients with Autism and Behavioral Disorders

• Somnolence occurs in approximately 51% of children, making it the most frequent adverse effect; administering the evening dose at bedtime can mitigate daytime sedation. 1, 2
• Headache affects 29% of pediatric patients treated with risperidone for disruptive behaviors. 1
• Vomiting occurs in 20% of children, along with dyspepsia in 15% of cases. 1
• Weight gain averages 2.7 kg over 8 weeks, with 15% of patients experiencing clinically significant weight increase and increased appetite reported in approximately 15-49% depending on the indication. 1, 2, 3
• Asymptomatic hyperprolactinemia is documented in children receiving risperidone, though clinical correlation with adverse events remains limited. 1, 2

Adult Patients with Schizophrenia

• Parkinsonism occurs in 14-17% of adults receiving risperidone 2-8 mg/day, compared to 8% with placebo. 3
• Akathisia affects 10% of patients at therapeutic doses (2-8 mg/day). 3
• Sedation is reported in 10% of adults, with dizziness in 7% and dystonia in 3-4%. 3
• Orthostatic hypotension occurs in 2% of patients, requiring blood pressure monitoring in both supine and standing positions when combining with antihypertensive medications. 4, 3

Patients with Bipolar Mania

• Parkinsonism is the most common extrapyramidal effect, occurring in 25% of adults with bipolar mania versus 9% on placebo. 3
• Sedation affects 11% of adults and 42-63% of pediatric patients with bipolar mania, showing marked age-related differences. 3
• Fatigue is reported in 18-30% of pediatric patients with bipolar disorder. 3

Dose-Dependent Adverse Effects

Extrapyramidal Symptoms Show Clear Dose-Response

• EPS incidence increases from 13% at placebo to 35% at 16 mg/day in fixed-dose trials, with Parkinsonism scores rising from 1.2 (placebo) to 2.6 (16 mg/day). 3
• At doses of 1-4 mg/day, EPS rates remain 7-12%, but escalate to 17-20% at 8-16 mg/day. 3
• Doses above 2.5 mg/day in children produce more adverse effects without improved efficacy, supporting conservative dosing strategies. 2
• The extrapyramidal symptom profile at therapeutic doses is comparable to placebo in pediatric trials, with no changes detected on electrocardiography. 1

Metabolic Effects Require Systematic Monitoring

• Risperidone is classified among second-generation antipsychotics with "more metabolic effects" on glucose metabolism, requiring fasting glucose screening at baseline, 12-16 weeks, and annually. 2
• Weight gain risk is similar to olanzapine, clozapine, and quetiapine, and significantly higher than aripiprazole, ziprasidone, or lurasidone. 2
• Metabolic syndrome associated with risperidone confers a 3- to 6-fold increased risk of diabetes and markedly higher cardiovascular morbidity. 2

Hepatic and Hematologic Considerations

• Baseline and periodic liver function monitoring is prudent in adolescents, as liver enzyme abnormalities and fatty infiltrates have been reported in adolescent males during therapy. 4
• Mean liver enzyme levels increase significantly after both 1 and 6 months of treatment, warranting periodic monitoring during maintenance therapy. 2
• A complete blood count with differential should be checked at baseline to screen for pre-existing hematological abnormalities. 2

Special Population Considerations

Children with Intellectual Disability

• Children with intellectual disability appear more sensitive to risperidone-related adverse effects, supporting conservative starting doses (0.25 mg/day if <20 kg; 0.5 mg/day if ≥20 kg) and slower titration schedules. 2
• When combined with stimulants, risperidone produces less somnolence, headaches, and vomiting, but more rhinitis and increased appetite compared to risperidone monotherapy. 1
• Stimulant co-administration does not prevent weight gain, with mean weight gain of 2.84 kg occurring irrespective of combined use. 1

Endocrine and Sexual Side Effects

• Hyperprolactinemia occurs asymptomatically in many patients, with similar rates whether risperidone is used alone or combined with stimulants. 1
• Clinical manifestations may include menstrual irregularities, amenorrhea, gynecomastia, galactorrhea, and sexual dysfunction including erectile dysfunction and ejaculation disorders. 3, 5

Cardiovascular Effects

• Blood pressure should be measured in both supine and standing positions when combining risperidone with hypotensive medications to detect orthostatic changes. 4, 6
• Heart rate increases and palpitations occur in <1-2% of patients. 3

Drug Interaction-Related Side Effects

• CYP2D6 inhibitors increase risperidone exposure, requiring monitoring for increased extrapyramidal symptoms and excessive sedation. 4, 6
• Concomitant use with other CNS-active medications or alcohol requires caution due to additive central nervous system depression and increased fall risk. 4, 6

Common Pitfalls to Avoid

• Do not ignore weight gain as a metabolic concern when combining risperidone with other weight-promoting medications like valproate or other atypical antipsychotics. 6
• Avoid combining with multiple sedating medications without careful monitoring, as additive CNS depression can impair function and increase fall risk. 6
• Do not assume absence of side effects means optimal dosing; children with ID/IDD may require doses lower than those used in typical development populations. 1