The Food and Drug Administration (FDA)-approved indications for oral risperidone (tablets, oral solution, and M-TABs) include the treatment of:

• Schizophrenia (in adults and children aged 13 and up)
• Bipolar I acute manic or mixed episodes as monotherapy (in adults and children aged 10 and up)
• Bipolar I acute manic or mixed episodes adjunctive with lithium or valproate (in adults)
• Autism-associated irritability (in children aged 5 and up). 

The long-acting risperidone injection has been approved for the use of schizophrenia and maintenance of bipolar disorder (as monotherapy or adjunctive to valproate or lithium) in adults.

There are many varied non-FDA-approved uses for risperidone. It has been used to treat psychotic symptoms when they are present. It has also been used for borderline personality, delusional disorder, delirium, depression, brain injury, pedophilia, PTSD, bipolar disorder, conduct disorder, Lesch-Nyhan, Tourette, trichotillomania, stuttering, movement disorders, and developmental disorders. In addition to psychotic symptoms, risperidone can be used for aggression and agitation in patients with dementia. Risperidone has also been used for augmentation of antidepressant therapy in the treatment of non-psychotic unipolar depression. In addition to irritability associated with autism, risperidone has also been used for social impairment, stereotypical behaviors, cognitive problems, and hyperactivity in autism.[1][2][3][4]

All antipsychotics have some degree of antagonism at D2 receptors. First-generation antipsychotics (FGAs) produce antipsychotic effects at 60% to 80% D2 occupancy. Second-generation antipsychotics (SGAs) like risperidone exhibit their therapeutic effects through some D2 blockade, but more from the blockade of serotonin receptors like 5HT2A. SGAs have loose binding to D2 receptors and can quickly dissociate from the receptor, potentially accounting for the lower likelihood of causing extrapyramidal symptoms (EPS). Moreover, SGAs have agonism at the 5HT1A receptor. Serotonin and norepinephrine reuptake inhibition are potential mechanisms by which risperidone is postulated to produce antidepressant effects. The improvement of positive symptoms is thought to be accomplished through the blockade of D2 receptors specifically in the mesolimbic pathway. The ability of antipsychotics to block D2 receptors in the prefrontal cortex and nucleus accumbens is important in improving certain psychiatric symptoms. Of note, risperidone does not cause anticholinergic effects, which may be of benefit for patients in certain populations including the elderly with dementia.

This medication may be administered in oral form (tablets, solution, or dissolvable M-TABs) or as a long-acting injection.

Weight changes, metabolic changes, and sedation are a significant concern with risperidone. Risperidone may produce extrapyramidal symptoms (EPS) which can include acute dystonia, akathisia, tardive dyskinesia (TD), and parkinsonian features. Acute/early EPS can occur at the beginning of treatment or when the dose is adjusted. Late-onset EPS (tardive dyskinesia) typically results from chronic treatment. Akathasia is a feeling of restlessness and may manifest as the patient pacing. Acute dystonia includes muscle spasms that result in abnormal postures and typically affect the head and neck. Parkinsonian features include skeletal muscle rigidity (often described as “cogwheel rigidity”), tremor, shuffling gait, and bradykinesia. Movements of the limbs, torso, neck, and head (commonly involving the tongue and lips) characterize tardive dyskinesia. This may also appear as facial grimacing or oculogyric crisis. EPS is thought to be due to D2 blockade in the nigrostriatal pathway. Since acute EPS symptoms often are improved with cessation of the medication, these side effects are a major cause of noncompliance with treatment. Although these side effects are thought to be reversible, the duration of parkinsonian features after discontinuation of the medication can be variable. Tardive dyskinesia, however, will likely persist after the medication is discontinued and may be permanent. In addition to discontinuation of the antipsychotic, pharmacologic treatments are available that may help with certain extrapyramidal symptoms.

Antagonism of D2 receptors in the tuberoinfundibular pathway is believed to precipitate a rise in prolactin level. The resulting hyperprolactinemia can precipitate sexual dysfunction which has a prevalence of 45-80 percent among males and 30% to 80% among females who are taking this medication. Further, the elevated prolactin can contribute to decreased libido, impaired arousal, and difficulty attaining an orgasm. Sexual side effects may also be precipitated by risperidone’s action at adrenergic (alpha 1, alpha 2) and histamine (H2) receptors. Gynecomastia, galactorrhea, as well as priapism, have been reported in male patients, while galactorrhea and amenorrhea have been reported in female patients. It is important to note that children may be more susceptible to certain susceptible to some side effects and should carefully be monitored.

Serious side effects of antipsychotic medications (like risperidone) can include neuroleptic malignant syndrome (NMS). Although the pathogenesis of NMS is not clear, it is a life-threatening condition that can manifest with altered mental status, fever, "lead pipe" rigidity, and autonomic instability including hypertension, tachypnea, and tachycardia. The use of risperidone has also been linked to a higher probability of cerebrovascular events in elderly patients with dementia, leading to an FDA warning about the use of this medication in the context of dementia-related psychosis. Studies have even shown an increase in all-cause mortality among the elderly with dementia who are on this medication.

Risperidone should not be given if a known allergy/hypersensitivity to risperidone or paliperidone (a metabolite or risperidone) is present. Hallucinogen persisting perception disorder or HPPD may be a relative contraindication for risperidone because some patients treated with risperidone for their HPPD reported that panic and visual symptoms intensified.