Risperidone

aliases: risperdal, rispond, risperdal consta, ריספרדל, ריספרדל קונסטה, ריספונד

In bipolar disorders, it is FDA-approved only for the acute phase of mania.
used off-label for prophylaxis of mania and bipolar disorder despite lack of FDA labeling for this indication.

Indications. Risperidone is indicated for the acute and maintenance treatment of schizophrenia in adults and the treatment of schizophrenia in adolescents ages 13 to 17 years. Risperidone is also indicated for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder in adults and children and adolescents ages 10 to 17 years. The combination of risperidone with lithium or valproate is indicated for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder.

Risperidone is also indicated for the treatment of irritability associated with an autistic spectrum disorder in children and adolescents ages 5 to 16 years, including symptoms of aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods.

Pharmacology. Risperidone is a benzisoxazole. It undergoes extensive first-pass hepatic metabolism to 9-hydroxy risperidone, a metabolite with equivalent antipsychotic activity. Peak plasma levels of the parent compound occur within 1 hour for the parent compound and 3 hours for the metabolite. Risperidone has bioactivity of 70 percent. The combined half-life of risperidone and 9-hydroxy risperidone averages 20 hours, so it is useful in once-daily dosing. Risperidone is an antagonist of the serotonin 5-HT2A, dopamine D2, α1-adrenergic and α2-adrenergic, and histamine H1 receptors. It has a low affinity for α-adrenergic and muscarinic cholinergic receptors. Risperidone is a potent antagonist of D2 receptors, as potent as haloperidol, however unlike haloperidol it causes less EPS.

Dosages. The recommended dose range and frequency of risperidone dosing have changed since the drug first came into clinical use. Risperidone is available in 0.25-, 0.5-, 1-, 2-, 3-, and 4-mg tablets and a 1-mg/mL oral solution. The initial dosage is usually 1 to 2 mg at night, which can then be increased to 4 mg/day. Positron emission tomography (PET) studies have shown that dosages of 1 to 4 mg/day provide the required D2 blockade for a therapeutic effect. At first, it was believed that because of its short elimination half-life, risperidone should be given twice a day, but studies have shown equal efficacy with once-a-day dosing. Dosages above 6 mg a day are associated with a higher incidence of adverse effects, particularly EPS. There is no correlation between plasma concentrations and therapeutic effects. Dosing guidelines for adolescents and children are different from those for adults, requiring lower starting dosages; higher dosages are associated with more adverse effects.

keypoint :: "- [i] 1 to 4 mg/day provide the required D2 blockade for a therapeutic effect"

Side Effects. The EPS of risperidone is largely dosage dependent, and there has been a trend to using lower doses than initially recommended. Weight gain, anxiety, nausea and vomiting, rhinitis, erectile dysfunction, orgasmic dysfunction, and increased pigmentation are associated with risperidone use. The most common drug-related reasons for discontinuation of risperidone use are EPS, dizziness, hyperkinesias, somnolence, and nausea. Marked elevation of prolactin may occur. Weight gain occurs more commonly with risperidone use in children than in adults.

Risperidone is also available as an orally disintegrating tablet (Risperdal M-Tab), which is available in 0.5, 1, and 2 mg strengths, and in a depot formulation (Risperdal Consta), which is given as an intramuscular (IM) injection formulation every 2 weeks. The dose may be 25, 50, or 75 mg. Oral risperidone should be coadministered with Risperdal Consta for the first 3 weeks before being discontinued.

Drug Interactions. Inhibition of CYP 2D6 by drugs such as paroxetine and fluoxetine can block the formation of risperidone’s active metabolite. Risperidone is a weak inhibitor of CYP2D6 and has little effect on other drugs. Combined use of risperidone and SSRIs may result in significant elevation of prolactin, with associated galactorrhea and breast enlargement.