Risperidone is an antipsychotic medication used to treat schizophrenia, bipolar disorder, and irritability associated with autism.
Also known as: risperidone, risperdal
CYP2D6 inhibitor SSRI + antipsychotic: risperidone levels increased 2-4-fold. Risk of extrapyramidal effects.
Fluoxetine is a potent CYP2D6 inhibitor (Ki ~0.2 μM), the main metabolic pathway for risperidone (70% of clearance). Co-administration increases risperidone levels 2-4-fold, depending on the patient's CYP2D6 phenotype. The risk of extrapyramidal effects (tremor, rigidity, parkinsonism) increases significantly. In severe cases, neuroleptic malignant syndrome may occur (hyperthermia >40°C, muscular rigidity, unconsciousness, autonomic instability). Fluoxetine has a long half-life (2-6 days) and its active metabolite (norfluoxetine) inhibits CYP2D6 for 2-3 weeks after discontinuation. The Portuguese Prontuário Terapêutico recommends reducing risperidone dose by 50% or switching to an antipsychotic not metabolised by CYP2D6 (e.g. aripiprazole, quetiapine).
CYP2D6 inhibitor SSRI + antipsychotic: risperidone levels increased 2-4-fold. Risk of EPS and neuroleptic malignant syndrome.
Fluoxetine is a potent CYP2D6 inhibitor (Ki ~0.2 μM), the main metabolic pathway for risperidone. Co-administration may increase risperidone levels 2-4-fold, increasing the risk of extrapyramidal effects, parkinsonism, and neuroleptic malignant syndrome.
Extrapyramidal effects, torticollis, rigidity.
Neuroleptic malignant syndrome (hyperthermia, rigidity, unconsciousness).
If possible, avoid. If necessary, reduce risperidone dose by 50% and monitor for extrapyramidal effects.
DailyMed/FDA
Mood stabiliser + antipsychotic: increased risk of EPS and neurotoxicity.
The combination is used therapeutically in acute mania and maintenance. However, the risk of extrapyramidal effects and neurotoxicity is additive. Lithium may potentiate EPS from antipsychotics. Monitor for neuroleptic malignant syndrome (hyperthermia, rigidity, unconsciousness). Maintain lithium levels within therapeutic range (0.6-1.0 mEq/L). Adjust doses as needed.
Mood stabiliser + antipsychotic: increased risk of EPS and neurotoxicity. Monitor for neuroleptic malignant syndrome.
The combination may increase the risk of extrapyramidal effects and neurotoxicity. Monitor for signs of neuroleptic malignant syndrome.
EPS, neurotoxicity signs.
Neuroleptic malignant syndrome.
Monitor for EPS and neurotoxicity signs (confusion, tremor, fever).
DailyMed/FDA
No documented food or drink interactions.
No documented disease interactions.
No documented pregnancy or breastfeeding information.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
D2 and 5-HT2A antagonist. Effect on positive and negative symptoms of schizophrenia.
Competitive antagonism of D2 receptors in the mesolimbic circuit (antipsychotic effect) and 5-HT2A in the cortex (improvement of negative symptoms).
Complete oral absorption. Bioavailability: 70%. Food does not affect extent.
Metabolised by CYP2D6 to 9-hydroxyrisperidone (active). CYP3A4 contributes secondarily.
3-6 h (risperidone); 17-24 h (9-hydroxyrisperidone).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
