Risperidone is effective in treating the acute exacerbations of schizophrenia.
Studies evaluating the utility of the oral form of risperidone for maintenance therapy have reached varying conclusions. A 2012 systematic review concluded that there is strong evidence 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 2010 Cochrane review found a slight benefit during the first few weeks of treatment of schizophrenia but the article raised concerns regarding bias favoring risperidone.
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.
Second generation antipsychotics, including risperidone, are effective in the treatment of manic symptoms in acute manic or mixed exacerbations of bipolar disorder. In children and adolescents, risperidone may be more effective than lithium or divalproex, but has more metabolic side effects. As maintenance therapy, aripiprazole is effective for the prevention of manic episodes but not depression. The long-acting injectable form of risperidone may be advantageous over long acting first generation antipsychotics, as it is better tolerated (fewer extrapyramidal effects) and because long acting injectable formulations of first generation antipsychotics may increase the risk of depression.
Compared to placebo, risperidone treatment reduces certain problematic behaviors in autistic children, including aggression toward others, self-injury, temper tantrums, and rapid mood changes. The evidence for its efficacy appears to be greater than that for alternative pharmacological treatments.Weight gain is an important adverse effect. Some authors recommend limiting the use of aripiprazole to those with the most challenging behavioral disturbances in order to minimize the risk of drug-induced adverse effects. Evidence for the efficacy of risperidone in autistic adolescents and young adults is less persuasive.
Risperidone provides no benefit in the treatment of eating disorders or personality disorders.
While antipsychotic medications such as risperidone have a slight benefit in people with dementia, they have been linked to higher incidences of death and stroke. Because of this increased risk of death, treatment of dementia-related psychosis with risperidone is not FDA approved.
Carbamazepine and other enzyme inducers may reduce plasma levels of risperidone.If a person is taking both carbamazepine and risperidone, the dose of risperidone will likely need to be increased. The new dose should not be more than twice the patient's original dose.
CYP2D6 inhibitors, such as SSRI medications, may increase plasma levels of risperidone.
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse. Some have argued the additional somatic and psychiatric symptoms associated with dopaminergic super-sensitivity, including dyskinesia and acute psychosis, are common features of withdrawal in individuals treated with neuroleptics. This has led some to suggest the withdrawal process might itself be schizomimetic, producing schizophrenia-like symptoms even in previously healthy patients, indicating a possible pharmacological origin of mental illness in a yet unknown percentage of patients currently and previously treated with antipsychotics. This question is unresolved, and remains a highly controversial issue among professionals in the medical and mental health communities, as well the public.
Older people with dementia-related psychosis are at a higher risk of death if they take risperidone compared to those who do not. Most deaths are related to heart problems or infections.
Risperidone is available as an oral tablet, oral dissolving tablet, or intramuscular injection. The intramuscular preparation, marketed as Risperdal Consta, can be given once every two weeks. It is slowly released from the injection site. This method of administration may be used on sanctioned patients (detained), who are refusing, or consenting patients who may have disorganized thinking and cannot remember to take their daily doses.
Risperidone undergoes hepatic metabolism and renal excretion. Lower doses are recommended for patients with severe liver and kidney disease.
Risperidone belongs as a chemical structure to a new antipsychotic medication chemical group called "benzioxazoles".
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. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT2C, linked to weight gain, 5-HT2A, linked to its antipsychotic action and relief of some of the extrapyramidal side effects experienced with the typical neuroleptics.
Dopamine receptors: This drug is an antagonist of the D1 (D1, and D5) as well as the D2 family (D2, D3 and D4) receptors. This drug has "tight binding" properties, which means it has a long half-life and 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 tremors, 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 breaks all of which are associated with increased prolactin secretion.
Serotonin receptors: Its action at these receptors may be responsible for its lower extrapyramidal side effect liability (via the 5-HT2A/2C receptors) and improved negative symptom control compared to typical antipsychotics such as haloperidol for instance. Its antagonistic actions at the 5-HT2C receptor may account, in part, for its weight gain liability.
Alpha α1 adrenergic receptors: This action accounts for its orthostatic hypotensive effects and perhaps some of the sedating effects of risperidone.
Risperidone was approved by the United States Food and Drug Administration (FDA) in 1994 for the treatment of schizophrenia. On August 22, 2007, risperidone was approved as the only drug agent available for treatment of schizophrenia in youths, ages 13–17; it was also approved that same day for treatment of bipolar disorder in youths and children, ages 10–17, joining lithium. Risperidone contains the functional groups 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. In 2003, the FDA approved risperidone for the short-term treatment of the mixed and manic states associated with bipolar disorder. In 2006, the FDA approved risperidone for the treatment of irritability in autistic children and adolescents. The FDA's decision was based in part on a study of autistic people with severe and enduring problems of violent meltdowns, aggression, and self-injury; risperidone is not recommended for autistic people with mild aggression and explosive behavior without an enduring pattern.
Janssen's patent on risperidone expired on December 29, 2003, opening the market for cheaper generic versions from other companies, and Janssen's exclusive marketing rights expired on June 29, 2004 (the result of a pediatric extension).
Risperidone is available as a tablet, an oral solution, and an ampule, Risperdal Consta, which is a depot injection administered once every two weeks. It is also available as a wafer known in the United States and Canada as Risperdal M-Tabs and elsewhere as Risperdal Quicklets. Risperidone is also available as paliperidone IM injections (a risperidone derivative). This injection is given 12 times a year on the same day each month.
Risperidone became available as a generic drug in October 2008 from Teva Pharmaceuticals, Dr. Reddy's Laboratories, Inc. and Patriot Pharmaceutics. The Patriot generic is an authorized generic pharmaceutical. The drug is currently marketed in India under several brand names including Risperdal, Risdon and Sizodon.
On 11 April 2012, Johnson & Johnson and its subsidiary Janssen Pharmaceuticals Inc. were fined $1.2 billion by Judge Timothy Davis Fox of the Sixth Division of the Sixth Judicial Circuit of the U.S. state of Arkansas. The jury found the companies had downplayed multiple risks associated with risperidone (Risperdal). The verdict was later reversed by the Arkansas State Supreme court.
According to the Wall Street Journal on June 20, 2012, "Johnson & Johnson and the U.S. Justice Department [we]re close to settling a protracted investigation into the company’s promotion of the antipsychotic Risperdal, for what would be one of the highest sums to date in a drug-marketing case. The sides are trying to wrap together a number of lawsuits, state investigations and other probes of alleged illegal marketing, and are discussing a payment of $1.5 billion or higher." The fine ultimately imposed totaled $2.2 billion.
^ abcdTruven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 18]. Greenwood Village, CO: Thomsen Healthcare; 2013.
^ abKomossa K, Rummel-Kluge C, Schwarz S, Schmid F, Hunger H, Kissling W, Leucht S (Jan 19, 2011). "Risperidone versus other atypical antipsychotics for schizophrenia.". The Cochrane database of systematic reviews (1): CD006626. doi:10.1002/14651858.CD006626.pub2. PMID21249678.
^Hasnain M, Vieweg WV, Hollett B (July 2012). "Weight gain and glucose dysregulation with second-generation antipsychotics and antidepressants: a review for primary care physicians". Postgraduate Medicine124 (4): 154–67. doi:10.3810/pgm.2012.07.2577. PMID22913904.
^ ab"Respiridone". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
^Leucht S, Cipriani A, Spineli L, et al. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet382 (9896): 951–62. doi:10.1016/S0140-6736(13)60733-3. PMID23810019.
^Osser DN, Roudsari MJ, Manschreck T (2013). "The psychopharmacology algorithm project at the Harvard South Shore Program: an update on schizophrenia". Harv Rev Psychiatry21 (1): 18–40. doi:10.1097/HRP.0b013e31827fd915. PMID23656760.
^Glick ID, Correll CU, Altamura AC, et al. (December 2011). "Mid-term and long-term efficacy and effectiveness of antipsychotic medications for schizophrenia: a data-driven, personalized clinical approach". J Clin Psychiatry72 (12): 1616–27. doi:10.4088/JCP.11r06927. PMID22244023.
^Rattehalli RD, Jayaram MB, Smith M (2010). Rattehalli, Ranganath, ed. "Risperidone versus placebo for schizophrenia". Cochrane Database Syst Rev (1): CD006918. doi:10.1002/14651858.CD006918. PMID20091611.
^Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S (April 2011). "Oral versus depot antipsychotic drugs for schizophrenia--a critical systematic review and meta-analysis of randomised long-term trials". Schizophr. Res.127 (1-3): 83–92. doi:10.1016/j.schres.2010.11.020. PMID21257294.
^Lafeuille MH, Dean J, Carter V, et al. (August 2014). "Systematic review of long-acting injectables versus oral atypical antipsychotics on hospitalization in schizophrenia". Curr Med Res Opin30 (8): 1643–55. doi:10.1185/03007995.2014.915211. PMID24730586.
^Nielsen J, Jensen SO, Friis RB, Valentin JB, Correll CU (September 2014). "Comparative Effectiveness of Risperidone Long-Acting Injectable vs First-Generation Antipsychotic Long-Acting Injectables in Schizophrenia: Results From a Nationwide, Retrospective Inception Cohort Study". Schizophr Bull. doi:10.1093/schbul/sbu128. PMID25180312.
^Muralidharan K, Ali M, Silveira LE, et al. (September 2013). "Efficacy of second generation antipsychotics in treating acute mixed episodes in bipolar disorder: a meta-analysis of placebo-controlled trials". J Affect Disord150 (2): 408–14. doi:10.1016/j.jad.2013.04.032. PMID23735211.
^Sharma A, Shaw SR (2012). "Efficacy of risperidone in managing maladaptive behaviors for children with autistic spectrum disorder: a meta-analysis". J Pediatr Health Care26 (4): 291–9. doi:10.1016/j.pedhc.2011.02.008. PMID22726714.
^McPheeters ML, Warren Z, Sathe N, et al. (May 2011). "A systematic review of medical treatments for children with autism spectrum disorders". Pediatrics127 (5): e1312–21. doi:10.1542/peds.2011-0427. PMID21464191.
^BMJ Group, ed. (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISSN0260-535X. Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
^ abcdBrunton L, Chabner B, Knollman B. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.
^Abou El-Magd RM, Park HK, Kawazoe T, Iwana S, Ono K, Chung SP, Miyano M, Yorita K, Sakai T, Fukui K (July 2010). "The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia". Journal of Psychopharmacology24 (7): 1055–1067. doi:10.1177/0269881109102644. PMID19329549.
^Scahill L (2008). "How do I decide whether or not to use medication for my child with autism? should I try behavior therapy first?". J Autism Dev Disord38 (6): 1197–8. doi:10.1007/s10803-008-0573-7. PMID18463973.