Description

Risperidone, sold under brand names such as Risperdal®, is an atypical antipsychotic medication. It belongs to the class of second-generation antipsychotics and is known for its potent antagonism of both dopamine D2 and serotonin 5-HT2A receptors. It is available in various formulations, including oral tablets, oral solution, and a long-acting injectable (LAI) form, which is used for maintenance therapy.

Indications

Risperidone has a broad range of approved indications for the treatment of both psychotic and mood disorders. Its main uses include:

• Schizophrenia: Treatment of acute and chronic schizophrenia, including first-episode psychosis.

• Bipolar Disorder:
  • Treatment of manic or mixed episodes associated with bipolar I disorder.

• • Maintenance treatment of bipolar I disorder, often as monotherapy or as an adjunctive to mood stabilizers.

• Irritability associated with Autistic Disorder: It is approved for the treatment of irritability, including aggression, self-injurious behavior, and temper tantrums, in children and adolescents with autism.

• Other Off-label Uses: It is also used off-label for a variety of conditions, including:
  • Behavioral disturbances in dementia

• • Agitation in various psychiatric conditions
  • Treatment-resistant depression (as an add-on therapy)

Mechanism of Action

Risperidone’s therapeutic effects are attributed to its strong and balanced antagonism of both dopamine and serotonin receptors.

1. Dopamine D2 Receptor Antagonism: Risperidone is a potent antagonist at dopamine D2 receptors. By blocking these receptors, it reduces the excessive dopaminergic activity that is believed to contribute to the positive symptoms of psychosis, such as hallucinations and delusions. Its affinity for the D2 receptor is strong, which contributes to its efficacy but also carries a dose-dependent risk of extrapyramidal symptoms (EPS), similar to first-generation antipsychotics.
2. Serotonin 5-HT2A Receptor Antagonism: Risperidone also has a very high affinity and acts as a potent antagonist at serotonin 5-HT2A receptors. Its affinity for this receptor is even higher than for the D2 receptor. This potent 5-HT2A antagonism is believed to be a key reason for its atypical profile, as it helps to alleviate both positive and negative symptoms of schizophrenia and may contribute to a lower overall risk of certain side effects compared to older antipsychotics.
3. Other Receptor Interactions: Risperidone also interacts with other receptors, which contribute to its overall effects and side-effect profile:

• • Alpha1-Adrenergic Receptor Antagonism: This can cause orthostatic hypotension (a drop in blood pressure when standing).

• • Histamine H1 Receptor Antagonism: This is responsible for its sedative effects.

In summary, risperidone’s balanced antagonism of dopamine D2 and serotonin 5-HT2A receptors is the key to its broad therapeutic efficacy in treating a range of psychiatric conditions. This dual action helps to manage both the positive symptoms of psychosis and the negative symptoms of schizophrenia.