Risperidone
Mechanism :
The mechanism of action of risperidone, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drugs therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism.
Indication :
- Schizophrenia
- Aggressive behaviour
- Attention deficit hyperactivity disorder (ADHD)
- Tourette syndrome
- Bipolar Mania
- Autism
Contraindications :
Do not use in patients with known hypersensitivity to phenothiazines. Do not use in comatose states or in the presence of large amounts of central nervous system depressants like alcohol, barbiturates and narcotics.
Dosing :
Aggressive behaviour, Tourette syndrome:
Oral: Once daily or in 2 divided doses.
2-12 years: 0.5-2 mg.
12-18 years: 1-4 mg.
Schizophrenia:
<13 years: Safety and efficacy not established.
>13 years: Initially 0.5 mg/day PO in the morning/evening; may be increased in increments of 0.5-1 mg/day to recommended dose of 2.5 mg/day (dose range: 0.5-6 mg/day). In case of persistent somnolence, divide daily dose 12 hourly.
Bipolar Mania:
Same dose as in schizophrenia but can be used in children >10 years OD age.
Autism:
<5 years:
Safety and efficacy not established.
5-16 years, <20 kg:
Initially 0.25 mg/day PO; after ≥4 days, it may be increased to recommended dosage of 0.5 mg/day.
5-16 years, ≥20 kg:
Initially 0.5 mg/day PO, after ≥4 days, it may be increased to recommended dosage of 1 mg/day.
In case of insufficient response, adjust dose every 2 weeks as follows:
<20 kg:
Increments of 0.25 mg/day. Maximum: 1 mg/day.
>20 kg:
Increments of 0.5 mg/day. Maximum: 2.5 mg/day.
Adverse Effect :
Somnolence, agitation, anxiety, akathisia, agitation, rhinitis, Parkinsonism, dyspepsia, constipation, dry mouth, fatigue and weight increase.
Interaction :
Fluoxetine and Paroxetine: Inhibits CYP 2D6, have been shown to increase the plasma concentration of risperidone.
Clozapine: Chronic administration of clozapine with risperidone may decrease the clearance of risperidone.
Cimetidine and Ranitidine: Increase the bioavailability of risperidone, but only marginally increased the plasma concentration of the active antipsychotic fraction.
May antagonize the effects of levodopa and dopamine agonists.
Because of its potential for inducing hypotension, may enhance the hypotensive effects of other therapeutic agents with this potential.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Initially 0.5 mg twice daily, increasing by 0.5 mg BD to 1–2 mg twice daily. Use with caution. |
| 10-20 | Initially 0.5 mg twice daily, increasing by 0.5 mg BD to 1–2 mg twice daily. Use with caution. |
| <10 | Initially 0.5 mg twice daily, increasing by 0.5 mg BD to 1–2 mg twice daily. Use with caution. |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in GFR<10 mL/min |
| HD | Dialysed. Dose as in GFR<10 mL/ min |
| HDF/High flux | Dialysed. Dose as in GFR<10 mL/ min |
| CAV/VVHD | Unlikely to be dialysed. Dose as in GFR=10–20 mL/min |
Hepatic Dose :
No specific paediatric dose adjustment is given, however recommendations are based on experience with adults. Due to hepatic metabolism, in hepatic impairment the mean plasma level of free fraction of risperidone may be increased by 35%.
Mild to moderate hepatic impairment: no dosage adjustment is recommended, but reduction of dose is reasonable.
Severe hepatic impairment: Daily dose should be halved. Titrate the dose weekly.