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:
Risperidone seems to produce somewhat more extrapyramidal side effects and clearly more prolactin increase than other atypical antipsychotics. It may also differ from other compounds in the occurrence of other adverse effects such as weight gain, metabolic problems, cardiac effects, sedation, and seizures. Nevertheless, the large proportion of participants leaving studies early and incomplete reporting of outcomes makes drawing firm conclusions difficult.
Findings in words
Findings in numbers
Quality of evidence
No clinically significant response
Risperidone is not clearly different when compared to olanzapine. Data supporting this finding are based on moderate-quality evidence.
On average, people receiving risperidone scored slightly higher (worse) than people treated with olanzapine but there was no clear difference between the groups. The meaning of this in day-to-day care is unclear. This finding is based on data of low quality.
Average QLS scale score (high = poor) Follow-up: over 26 weeks
On average, people receiving risperidone scored higher than people treated with olanzapine. There was no clear difference between the groups. The meaning of this in day-to-day care is unclear. This finding is based on data of moderate quality.
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, long-acting injectable risperidone is effective for the prevention of manic episodes but not depressive episodes. 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, challenging behaviour, 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 risperidone and 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.
While antipsychotic medications such as risperidone have a slight benefit in people with dementia, they have been linked to higher incidence of death and stroke. Because of this increased risk of death, treatment of dementia-related psychosis with risperidone is not FDA approved and carries a black box warning. However many other jurisdictions regularly use it to control severe aggression and psychosis in those with dementia when other non-pharmacological interventions have failed and their pharmaceutical regulators have approved its use in this population.
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.
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 and those medications.
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 as the public.
Older people with dementia-related psychosis are at a higher risk of death.
Dopamine receptors: This drug is an antagonist of the D1 (D1, and D5) as well as the D2 family (D2, D3 and D4) 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 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.
Risperidone was approved by the United States Food and Drug Administration (FDA) in 1993 for the treatment of schizophrenia. 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. On 22 August 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.
On 16 December 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Okedi, intended for the treatment of schizophrenia in adults for whom tolerability and effectiveness has been established with oral risperidone. The applicant for this medicinal product is Laboratorios Farmacéuticos Rovi, S.A. Risperidone was approved for medical use in the European Union in February 2022.
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 awarded a Pennsylvania man $8 billion in a verdict against J&J.
Janssen's patent on risperidone expired in December 2003, opening the market for cheaper generic versions from other companies, and Janssen's exclusive marketing rights expired in June 2004 (the result of a pediatric extension). It is available under many brand names worldwide.
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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