Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Risperidone is not approved for the treatment of patients with dementia-related psychosis.
Dementia-Related Psychosis: Cerebrovascular adverse events (e.g., stroke, transient ischemia attack), including fatalities, were reported in risperidone trials involving elderly patients (mean age 85 years; range 73 to 97) with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with risperidone compared to patients treated with placebo.
Neuroleptic Malignant Syndrome (NMS): There have been reports of NMS, a potentially fatal symptom complex, in association with antipsychotic drugs. Clinical manifestations include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. While there is no general agreement about specific pharmacological treatment of NMS, its management should include: (1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy: (2) intensive symptomatic treatment and medical monitoring; and (3) treatment of any concomitant serious medical problems for which specific treatments are available. If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. Careful monitoring of patients is necessary since recurrences of NMS have been reported.
Tardive Dyskinesia: Patients treated with antipsychotic drugs may develop tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements. The risk of developing this syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. The syndrome can also develop, although much less commonly, after relatively brief treatment periods at low doses. There is no known treatment for established cases of tardive dyskinesia. However, there may be partial or complete remission after withdrawal of antipsychotic treatment. Antipsychotic treatment may suppress or partially suppress the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Risperidone should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Reserve chronic antipsychotic treatment for patients who suffer from a chronic illness known to respond to antipsychotic drugs, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. Use the smallest dose and the shortest possible duration of treatment in patients who require chronic treatment. Periodically reassess the need for continued treatment. If signs and symptoms of tardive dyskinesia appear in a patient treated with risperidone, drug discontinuation should be considered. However, some patients may require treatment with risperidone despite the presence of the syndrome.
Seizures: Risperidone should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.
Potential for Cognitive and Motor Impairment: Risperidone is commonly associated with somnolence and has the potential to impair judgment, thinking or motor skills. Caution patients about operating hazardous machinery (including automobiles) until they are reasonably certain that risperidone therapy does not affect them adversely.
Suicide: Close supervision of high-risk patients is recommended since the possibility of a suicide attempt is inherent in patients with schizophrenia and bipolar mania, including children and adolescents. Prescribe risperidone in the smallest quantity of tablets consistent with good patient management to reduce the risk of overdose.
Orthostatic Hypotension: Risperidone may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, particularly during the initial dose-titration period, due to its α-adrenergic antagonistic properties. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive drugs. Risperidone should be used with caution in patients with known cardiovascular disease (e.g., heart failure, myocardial infarction or ischemia, conduction abnormalities, dehydration, hypovolemia, or cerebrovascular disease), and the dosage should be gradually titrated as recommended. A dose reduction should be considered if hypotension occurs. Special care should be exercised in patients taking drugs to lower blood pressure.
Venous Thromboembolism (VTE): Antipsychotic drugs have been reported to cause VTE. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with risperidone and preventive measures undertaken.
Hyperglycemia and Diabetes Mellitus: There have been reports of severe hyperglycemia, sometimes associated with ketoacidosis, hyperosmolar coma, or death, in patients receiving certain atypical antipsychotic agents, including risperidone. Patients with pre-existing diabetes mellitus who are started on atypical antipsychotics, including risperidone, should be monitored regularly for worsening of glucose control; those with risk factors for diabetes (e.g., obesity, family history of diabetes) should undergo fasting blood glucose testing upon therapy initiation and periodically throughout treatment. Any patient who develops manifestations of hyperglycemia (e.g., polydipsia, polyuria, polyphagia, and weakness) during treatment with an atypical antipsychotic should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic, including risperidone, was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of risperidone.
Weight Gain: Significant weight gain has been reported. Monitoring of weight gain is recommended during risperidone therapy. Patients may be advised to refrain from excessive eating in view of the possibility of weight gain.
Hyperprolactinemia: Risperidone and other drugs that antagonize dopamine D2 receptors elevate prolactin levels which persist during chronic use. Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents. Tissue culture studies suggest that cell growth in human breast tumors may be stimulated by prolactin. Although no clear association with the administration of antipsychotics has so far been shown in clinical and epidemiological studies, caution is recommended in patients with relevant medical history. Risperidone should be used with caution in patients with pre-existing hyperprolactinemia and in patients with possible prolactin-dependent tumors.
Priapism: Priapism may occur with risperidone treatment due to its α-adrenergic blocking effects. Severe priapism may require surgical intervention.
Leukopenia, Neutropenia and Agranulocytosis: Events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including risperidone. Agranulocytosis has also been reported. Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of risperidone should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (ANC<1,000/mm3) should discontinue risperidone and have their WBC monitored until recovery.
Thrombotic Thrombocytopenic Purpura (TTP): TTP has been reported in a patient receiving risperidone but the relationship with risperidone treatment is unknown.
Dysphagia: Esophageal dysmotility and aspiration have been associated with the use of antipsychotic drugs. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer's dementia. Use risperidone and other antipsychotic drugs with caution in patients at risk for aspiration pneumonia.
Antiemetic Effect: Risperidone may have antiemetic effects and may mask signs and symptoms of overdosage with certain drugs or of conditions such as intestinal obstruction, Reye's syndrome and brain tumor.
Body Temperature Regulation: Antipsychotic drugs, including risperidone, may cause disruption of body temperature regulation such as hyperthermia or hypothermia. Caution is advised when prescribing for patients who will be exposed to temperature extremes.
Use in Patients with Concomitant Illness: Patients with Parkinson's Disease or dementia with lewy bodies may have increased sensitivity to antipsychotic drugs, including risperidone. Increased sensitivity may manifest as confusion, obtundation, postural instability with frequent falls, EPS, and clinical features consistent with NMS. Use caution when administering risperidone in patients with diseases or conditions that could affect metabolism or hemodynamic responses. Risperidone has not been evaluated or used to any appreciable extent in patients with recent history of myocardial infarction or unstable heart disease. As with other antipsychotics, caution should be exercised when risperidone is prescribed in patients with a history of cardiac arrhythmias, in patients with congenital long QT syndrome, and in concomitant use with drugs known to prolong the QT interval such as class I antiarrhythmics (e.g., quinidine, disopyramide, procainamide), class III antiarrhythmics (e.g., amiodarone, sotalol), tricyclic antidepressant (TCA) (amitriptyline), tetracyclic antidepressants (maprotiline), some antihistamines, other antipsychotics, some antimalarials (e.g., chinice and mefloquine), and with medicines causing electrolyte imbalance (e.g., hypokalemia, hypomagnesemia), bradycardia, or those which inhibit the hepatic metabolism of risperidone. A lower starting dose is recommended in patients with severe renal impairment (CLCR <30 mL/min/1.73 m2) and in patients with severe hepatic impairment. (see Dosage & Administration).
Use in Children: Before risperidone is prescribed to a child or adolescent with conduct disorder, they should be fully assessed for physical and social causes of aggression behavior (e.g., pain or inappropriate environmental demands). Close monitoring of the sedative effects of risperidone in this population is recommended because of possible consequences on learning ability. A change in time of administration of risperidone could improve the impact of sedation on attention faculties of children and adolescents. Regular evaluation of endocrinological status, including measurements of height, weight, sexual maturation, monitoring of menstrual functioning, and other potential prolactin-related effects, is recommended because of the potential effects of prolonged hyperprolactinemia on growth and sexual maturation in children and adolescents.
Regular examination of EPS and other movement disorder should also be conducted during treatment with risperidone.
The safety and effectiveness of risperidone in children less than 13 years old with schizophrenia have not been established.
The safety and effectiveness of risperidone in children less than 10 years old with bipolar disorder have not been established.
The safety and effectiveness of risperidone in pediatric patients less than 5 years old with autistic disorder have not been established.