Risperidone

Risperidone is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection into a muscle. The injectable formulation is long-acting (depot) and lasts for about two weeks.

Pharmacodynamics

The main action of risperidone is to reduce the activity of dopaminergic and serotonergic pathways in the brain, thereby reducing symptoms of schizophrenia and mood disorders. Risperidone has a high binding affinity for serotonergic 5-HT2A receptors compared to dopaminergic D2 receptors in the brain. Risperidone binds to D2 receptors with lower affinity than first-generation antipsychotics, which bind with very high affinity. A reduction in extrapyramidal symptoms with risperidone compared to its predecessors is likely a result of its moderate affinity for dopaminergic D2 receptors.

Pharmacokinetics

Risperidone is subject to hepatic metabolism and renal excretion. Lower doses are recommended for patients with severe hepatic and renal disease. The active metabolite of risperidone, paliperidone, is also used as an antipsychotic. The absolute oral bioavailability of risperidone is 70%.

Drug Interactions

• Carbamazepine and other enzyme inducers may reduce plasma levels of risperidone. If a person is taking both carbamazepine and risperidone, the dose of risperidone must be increased.
• CYP2D6 inhibitors, such as SSRI antidepressants, may increase the plasma levels of risperidone.
• Because risperidone can cause hypotension, risperidone use should be monitored closely if a patient is taking concomitant antihypertensive medications to avoid a severe drop in blood pressure.
• Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St. John's wort.

Side effects

Common side effects include movement disorders, drowsiness, dizziness, visual disturbances, constipation, and weight gain. Approximately 9% to 20% of patients gained more than 7% of baseline weight, depending on the dose.

Serious side effects include potentially permanent movement disorder tardive dyskinesia as well as neuroleptic malignant syndrome, increased risk of suicide, and high blood glucose levels.

In the elderly with psychosis secondary to dementia, it may increase the risk of death.

While atypical antipsychotics appear to have a lower rate of movement problems compared to typical antipsychotics, risperidone has a high risk of movement problems among atypicals. However, atypical antipsychotics are associated with greater weight gain.

Toxicological Data

LD50 (rat, oral): 56.6 mg-kg-1