What are the side effects of risperidone?

Side Effects of Risperidone

Risperidone causes a distinct adverse-effect profile dominated by extrapyramidal symptoms, hyperprolactinemia, weight gain, and sedation, with the specific pattern and severity varying by dose, age, and indication. 1, 2

Common Side Effects in Adults with Schizophrenia

The most frequently reported adverse reactions in adults include:

• Parkinsonism occurs in 14-17% of patients at therapeutic doses (versus 8% with placebo), manifesting as extrapyramidal disorder, musculoskeletal stiffness, bradykinesia, muscle rigidity, and masked facies 2
• Akathisia (restlessness) affects 10% of patients at therapeutic doses compared to 3% with placebo 2
• Sedation is reported in 10% of patients (versus 2% placebo), though this is less than with clozapine or quetiapine 2, 3
• Dizziness occurs in 7% (versus 4% placebo) 2
• Weight gain is common, though less than with olanzapine or clozapine but more than with aripiprazole or ziprasidone 1, 3
• Dystonia affects 3-4% of patients (versus 2% placebo), including muscle spasms and oculogyration 2

Pediatric-Specific Adverse Effects

Children experience a different and often more pronounced side-effect profile:

• Somnolence is the most common adverse effect, occurring in approximately 51% of children treated for behavioral disorders; administering the evening dose at bedtime reduces daytime sedation 1
• Headache affects approximately 29% of pediatric patients 1
• Vomiting occurs in approximately 20% of children, with dyspepsia in an additional 15% 1
• Weight gain averages 2.7 kg over 8 weeks, with 15% experiencing clinically significant gain and increased appetite noted in 15-49% depending on indication 1
• Appetite suppression and sleep problems occur when combined with stimulants, similar to stimulant monotherapy 4

Dose-Dependent Extrapyramidal Effects

Extrapyramidal symptoms increase in a clear dose-dependent manner:

• At 2 mg/day, parkinsonism scores average 0.9 with 17% EPS incidence 2
• At 6 mg/day, parkinsonism scores rise to 1.8 with 21% EPS incidence 2
• At 16 mg/day, parkinsonism scores reach 2.6 with 35% EPS incidence 2
• Doses exceeding 2.5 mg/day in children generate more adverse effects without added efficacy 1
• At therapeutic pediatric doses, the extrapyramidal symptom profile is comparable to placebo 1

Endocrine and Metabolic Effects

Risperidone has pronounced effects on prolactin and metabolism:

• Hyperprolactinemia is universal and more pronounced than with most other atypical antipsychotics (except amisulpride), though often asymptomatic 1, 3, 5
• Sexual dysfunction includes amenorrhea (approximately 30% of premenopausal women), erectile dysfunction, retrograde ejaculation, galactorrhea, and gynecomastia 2, 6, 5
• Metabolic syndrome risk is similar to olanzapine, clozapine, and quetiapine, conferring a 3- to 6-fold increased risk of diabetes and markedly higher cardiovascular morbidity 1
• Weight gain is less than olanzapine or clozapine but more than amisulpride, aripiprazole, or ziprasidone 1, 3

Cardiovascular Effects

• Orthostatic hypotension occurs in 2% of adults (versus 0% placebo) 2
• Tachycardia and QTc prolongation are less pronounced than with sertindole 3
• Blood pressure should be measured both supine and standing when combined with hypotensive agents 1, 7

Hepatic and Hematologic Effects

• Liver enzyme elevations occur, with mean levels rising significantly after 1 month and 6 months of therapy 1
• Fatty liver infiltrates have been reported in adolescent males 1, 7
• Baseline and periodic liver function testing is advised in adolescents 1, 7
• A complete blood count with differential should be obtained at baseline 1

Other Notable Adverse Effects

• Rhinitis is more common with risperidone than conventional antipsychotics (NNH 3) 8
• Nasal congestion affects 4-6% of adults 2
• Seizure risk is lower than with clozapine (NNT 14 to prevent one seizure) 3
• Sedation is less than clozapine and quetiapine 3
• Minimal anticholinergic effects distinguish risperidone from low-potency typical antipsychotics 5

Special Population: Intellectual Disability

Children with intellectual disability demonstrate heightened sensitivity to risperidone:

• A starting dose of 0.25 mg/day if weight < 20 kg and 0.5 mg/day if weight ≥ 20 kg is recommended, with slower titration 1
• When combined with stimulants, these patients experience less somnolence, headache, and vomiting but more rhinitis and increased appetite 1
• Stimulant co-administration does not prevent weight gain (mean gain ≈ 2.8 kg) 1

Monitoring Requirements

Metabolic Monitoring

• Fasting glucose at baseline, 12-16 weeks, and annually thereafter 1
• Weight at each visit, with particular attention to clinically significant gain (≥7% baseline weight) 1

Hepatic Monitoring

• Baseline liver function tests in all patients 7
• Periodic monitoring during maintenance, especially in adolescents 1, 7

Hematologic Monitoring

• Baseline complete blood count to screen for pre-existing abnormalities 1

Cardiovascular Monitoring

• Orthostatic vital signs when combined with hypotensive medications 1, 7
• ECG may be indicated based on individual risk factors 7

Drug Interaction-Related Adverse Effects

• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) increase risperidone exposure, requiring monitoring for increased extrapyramidal symptoms and excessive sedation 1, 7
• CNS-active medications or alcohol cause additive central nervous system depression and heightened fall risk 1, 7

Critical Clinical Pitfalls

• Do not disregard weight gain when risperidone is combined with other weight-promoting agents (e.g., valproate, other atypical antipsychotics) 1
• Avoid combining multiple sedating drugs without careful monitoring; additive CNS depression impairs function and increases fall risk 1
• Absence of observable side effects does not guarantee optimal dosing; children with intellectual/developmental disabilities may require lower doses than typically developing peers 1
• Women with amenorrhea may assume they are menopausal and discontinue birth control; counsel that menses may resume if risperidone is reduced or switched 6
• Retrograde ejaculation in men is related to strong alpha-1 adrenergic blockade and may be intolerable, requiring medication adjustment 6