Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic^[2] used to treat schizophrenia and bipolar disorder,^[2] as well as aggressive and self-injurious behaviors associated with autism spectrum disorder.^[8] It is taken either by mouth or by injection (i.e., subcutaneous or intramuscular).^[2] The injectable versions are long-acting and last for 2–4 weeks.^[9]

Common side effects include weight gain, drowsiness, fatigue, insomnia, dry mouth, constipation, elevated prolactin levels, and restlessness.^[2][10] Serious side effects may include the potentially permanent movement disorder tardive dyskinesia, as well as neuroleptic malignant syndrome, an increased risk of suicide, and high blood sugar levels.^[2][9] In older people with psychosis as a result of dementia, it may increase the risk of death.^[2] It is unknown if it is safe for use in pregnancy.^[2] Its mechanism of action is not entirely clear, but is believed to be related to its action as a dopamine and serotonin antagonist.^[2]

Study of risperidone began in the late 1980s and it was approved for sale in the United States in 1993.^[2][8][6] It is on the World Health Organization’s List of Essential Medicines.^[11] It is available as a generic medication.^[9] In 2023, it was the 176th most commonly prescribed medication in the United States, with more than 2 million prescriptions.^[12][13]

Risperidone is mainly used for the treatment of schizophrenia, bipolar disorder, and irritability associated with autism.^[14]

Risperidone is effective in treating psychogenic polydipsia and the acute exacerbations of schizophrenia.^[15][16]

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.^[17] 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.^[18] 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.^[19] A 2011 Cochrane review compared risperidone with other atypical antipsychotics such as olanzapine for schizophrenia, concluding it produced a somewhat higher risk of extrapyramidal side effects.^[20]

Long-acting injectable formulations of antipsychotic drugs provide improved compliance with therapy and reduce relapse rates relative to oral formulations.^[21][22] The efficacy of risperidone long-acting injection appears to be similar to that of long-acting injectable forms of first-generation antipsychotics.^[23]

Second-generation antipsychotics, including risperidone, are effective in the treatment of manic symptoms in acute manic or mixed exacerbations of bipolar disorder.^[24][25][26] In children and adolescents, risperidone may be more effective than lithium or valproate, but has more metabolic side effects.^[27] As maintenance therapy, long-acting injectable risperidone is effective for the prevention of manic episodes but not depressive episodes.^[28] 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.^[29]

Compared to placebo, risperidone treatment reduces certain problematic behaviors in autistic children, including aggression toward others, self-injury, challenging behavior, and rapid mood changes.^[30] The evidence for its efficacy appears to be greater than that for alternative pharmacological treatments.^[31] Weight gain is an important adverse effect.^[6][32] Some authors recommend limiting the use of risperidone and aripiprazole to those with the most challenging behavioral disturbances to minimize the risk of drug-induced adverse effects.^[33] Evidence for the efficacy of risperidone in autistic adolescents and young adults is less persuasive.^[34]

While antipsychotic medications such as risperidone have a slight benefit in people with dementia, they have been linked to a higher incidence of death and stroke.^[35] Because of this increased risk of death, treatment of dementia-related psychosis with risperidone is not FDA-approved and carries a black box warning.^[6] 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.^[36][37]