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Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as aggressive and self-injurious behaviors associated with autism spectrum disorder. It is taken either by mouth or by injection (i.e., subcutaneous or intramuscular). The injectable versions are long-acting and last for 2–4 weeks.
Common side effects include weight gain, Somnolence, fatigue, insomnia, dry mouth, constipation, elevated prolactin levels, and Akathisia. Serious side effects may include the potentially permanent movement disorder tardive dyskinesia, as well as neuroleptic malignant syndrome, an increased risk of suicide, and hyperglycemia. In older people with psychosis as a result of dementia, it may increase the risk of death. It is unknown if it is safe for use in pregnancy. Its mechanism of action is not entirely clear, but is believed to be related to its action as a dopamine and serotonin antagonist.
Study of risperidone began in the late 1980s and it was approved for sale in the United States in 1993.
It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2022, it was the 183rd most commonly prescribed medication in the United States, with more than 2million prescriptions.
Studies evaluating the utility of risperidone by mouth for maintenance therapy have reached varying conclusions. A 2012 systematic review concluded that evidence is strong that risperidone is more effective than all first-generation antipsychotics other than haloperidol, but that evidence directly supporting its superiority to placebo is equivocal. A 2011 review concluded that risperidone is more effective in relapse prevention than other first- and second-generation antipsychotics with the exception of olanzapine and clozapine. A 2016 Cochrane review suggests that risperidone reduces the overall symptoms of schizophrenia, but firm conclusions are difficult to make due to very low-quality evidence. Data and information are scarce, poorly reported, and probably biased in favour of risperidone, with about half of the included trials developed by drug companies. The article raises concerns regarding the serious side effects of risperidone, such as parkinsonism. A 2011 Cochrane review compared risperidone with other atypical antipsychotics such as olanzapine for schizophrenia:
Long-acting injectable formulations of antipsychotic drugs provide improved compliance with therapy and reduce relapse rates relative to oral formulations. The efficacy of risperidone long-acting injection appears to be similar to that of long-acting injectable forms of first-generation antipsychotics.
Risperidone has shown promise in treating therapy-resistant obsessive–compulsive disorder, when serotonin reuptake inhibitors alone are not sufficient.
Risperidone has proven to be effective in treatment of aggression associated with attention deficit hyperactivity disorder (ADHD), or with another mental condition.
Risperidone has not demonstrated a benefit in the treatment of eating disorders or personality disorders, except for limited evidence in schizotypal personality disorder.
While atypical antipsychotics appear to have a lower rate of movement problems as compared to typical antipsychotics, risperidone has a high risk of movement problems among the atypicals. Atypical antipsychotics, however, are associated with a greater amount of weight gain and other metabolic side effects.
Risperidone has been classified as a "qualitatively atypical" antipsychotic agent with a relatively low incidence of extrapyramidal side effects (when given at low doses) that has more pronounced serotonin antagonism than dopamine antagonism. Risperidone contains the of benzisoxazole and piperidine as part of its molecular structure. Although not a butyrophenone, it was developed with the structures of benperidol and ketanserin as a basis. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT2C, linked to weight gain, and 5-HT2A, linked to its antipsychotic action and relief of some of the extrapyramidal side effects experienced with typical antipsychotics.Brunton L, Chabner B, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.
It has been found that D-amino acid oxidase, the enzyme that catalyses the breakdown of D-amino acids (e.g. D-alanine and D-serine — the neurotransmitters) is inhibited by risperidone.
Risperidone acts on the following receptors:
Dopamine receptors: This drug is an antagonist of the D1 (D1, and D5) as well as the D2 (D2, D3 and D4) family receptors, with 70-fold selectivity for the D2 family. It has "tight binding" properties, which means it has a long half-life. Like other antipsychotics, risperidone blocks the mesolimbic pathway, the prefrontal cortex limbic pathway, and the tuberoinfundibular pathway in the central nervous system. Risperidone may induce extrapyramidal side effects, akathisia and , which is associated with diminished dopaminergic activity in the striatum. It can also cause sexual side effects, galactorrhoea, infertility, gynecomastia, and, with chronic use, reduced bone mineral density leading to Bone fracture, all of which are associated with increased prolactin secretion.
Alpha α1 adrenergic receptors: This action accounts for the orthostatic hypotensive effects and perhaps some of the sedating effects of risperidone.
Alpha α2 adrenergic receptors: Risperidone's action at these receptors may cause greater positive, negative, affective, and cognitive symptom control.
Histamine H1 receptors: effects on these receptors account for its sedation and reduction in vigilance. This may also lead to drowsiness and weight gain.
Voltage-gated sodium channels: Because it accumulates in synaptic vesicles, Risperidone inhibits voltage-gated sodium channels at clinically used concentrations.
On 16 December 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) formally recommended market authorization for Okedi, a long-acting depot injection of risperidone. Okedi was approved for the treatment of schizophrenia in adults for whom the tolerability and effectiveness of risperidone had already been established using an oral formulation. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Long-acting depot injectable risperidone was approved for medical use in the European Union in February 2022.
In August 2012, J&J agreed to pay $181 million to 36 US states to settle claims that it had promoted risperidone and paliperidone for including for dementia, anger management, and Anxiety disorder.
In November 2013, J&J was fined $2.2 billion for illegally marketing risperidone for use in people with dementia and paying kickbacks to prescribing physicians and nursing home pharmacies.
In 2015, Steven Brill wrote an investigative journalism piece about J&J in The Huffington Post focused on J&J's marketing of risperidone.
J&J has faced numerous civil lawsuits on behalf of children who were prescribed risperidone who grew breasts (a condition called gynecomastia); as of July 2016 there were about 1,500 cases in Pennsylvania state court in Philadelphia, and there had been a February 2015 verdict against J&J with $2.5 million awarded to a man from Alabama, a $1.75 million verdict against J&J that November, and in 2016 a $70 million verdict against J&J. In October 2019, a jury ordered J&J to pay $8 billion in punitive damages to a Pennsylvania man who had grown breasts during adolescence. This verdict amount chosen by the jury was reduced more than 1,000-fold by a judge in January 2020, with the new punitive damages being $6.8 million. A legal scholar commented that punitive damages which exceed the compensatory damages by a factor of 10 or more in cases of this type are usually found to be legally invalid.
Risperidone is available as a tablet, an oral solution, and an ampule, which is a depot injection.
Brand names include Risperdal, Risperdal Consta, Risperdal M-Tab, Risperdal Quicklets, Risperlet, Okedi, and Perseris.
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