Risperidon
Use in elderly patients with dementia
Increased mortality in older patients with dementia
Elderly patients with dementia treated with atypical antipsychotics experienced increased mortality compared with placebo in studies of atypical antipsychotics, including risperidone. When using risperidone in this population, the incidence of death was 4% for patients taking risperidone, compared with 3.1% for placebo. The mean age of patients who died was 86 years (range, 67–100 years). Data collected from two large observational studies show that older patients with dementia treated with typical antipsychotic medications also have a slightly increased risk of death compared with patients not treated. At present, insufficient data have been collected to accurately assess this risk. The reason for the increase in this risk is also unknown. Also unknown is the extent to which the increased mortality may be attributable to antipsychotic drugs rather than to the characteristics of this patient population.
Combined use with furosemide
For older patients with dementia taking oral risperidone, there was an increased mortality rate among patients taking furosemide and risperidone (7.3%; mean age 89 years, range 75-97 years) compared with those taking risperidone alone (3.1 %, mean age 84 years, range 70-96 years) and the furosemide-only group (4.1%, mean age 80 years, range 67-90 years). An increase in mortality in patients taking risperidone with furosemide was observed in 2 of 4 clinical studies. Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with an increase in mortality. No pathophysiological mechanisms have been established to explain this observation. However, special care should be taken when using the drug in such cases. Before prescribing, the risk/benefit ratio must be carefully assessed. There was no increase in mortality in patients taking other diuretics concomitantly with risperidone. Regardless of treatment, in older patients with dementia, dehydration is a common risk factor for mortality and should be carefully monitored. Regardless of treatment, dehydration is a common risk factor for mortality and should be carefully monitored in older patients with dementia.
An increase in cerebrovascular adverse events (acute and transient cerebrovascular events), including deaths, including deaths (mean age 85 years, range 73-97 years) was observed when risperidone was used compared with placebo in elderly patients with dementia. Therefore, risperidone should be used with caution in patients at risk of stroke.
Cardiovascular effects
In placebo-controlled clinical trials, an approximately 3-fold increased risk of cerebrovascular side effects was observed in patients with dementia taking certain atypical antipsychotic drugs.
Pooled data from 6 placebo-controlled studies involving primarily elderly patients with dementia (age >65 years) demonstrate that cerebrovascular adverse events (serious and non-serious) occurred in 3.3% (33/1009) of patients treated with risperidone. and in 1.2% (8/712) of patients receiving placebo. The risk ratio was 2.96 (1.34, 7.50) with a 95% confidence interval. The mechanism by which this risk increases is unknown. An increased risk cannot be excluded for other antipsychotic drugs, as well as for other patient populations. Risperidone should be used with caution in patients with risk factors for stroke. The risk of cerebrovascular side effects is much higher in patients with mixed or vascular dementia compared to patients with Alzheimer's type dementia. Therefore, patients with any type of dementia other than Alzheimer's type dementia should not take risperidone. Clinicians should evaluate the risk/benefit ratio of risperidone in older patients with dementia, taking into account the predictors of stroke risk individually for each patient. Patients and caregivers should be cautioned to immediately report signs and symptoms of cardiovascular events, such as sudden weakness or stiffness/numbness in the face, legs, arms, as well as difficulty speaking and vision problems. In this case, all possible treatment options should be considered, including discontinuation of the drug. Risperidone should only be used for the short-term treatment of persistent aggression in patients with moderate to severe Alzheimer's dementia, as an adjunct to non-pharmacological treatments when they are ineffective or limited in effectiveness, and when there is a risk of harm to the patient to himself or others . Patients' condition and the need for continued risperidone therapy should be continually assessed.
Switching from therapy with other antipsychotic drugs
When initiating treatment with risperidone for schizophrenia, if clinically warranted, it is recommended to gradually withdraw previous therapy. However, if patients are transferred from therapy with depot forms of antipsychotic drugs, it is recommended to start risperidone therapy instead of the next scheduled injection. The need for continued therapy should be assessed periodically. Orthostatic hypotension.
Due to the α-adrenergic blocking effect of risperidone, orthostatic hypotension may occur, especially during the initial dose titration period. A clinically significant decrease in blood pressure in the post-marketing period is observed with simultaneous use of risperidone with antihypertensive drugs. If blood pressure decreases, consider reducing the dose of one or both drugs. In patients with known cardiovascular disease (heart failure, myocardial infarction, cardiac conduction disturbances, dehydration, hypovolemia or cerebrovascular disease), as well as dehydration, hypovolemia or cerebrovascular disease, the dose should be increased gradually as recommended.
Extrapyramidal symptoms and tardive dyskinesia.
Drugs with dopamine receptor antagonist properties can cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, mainly of the tongue and/or facial muscles. The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If a patient experiences objective or subjective symptoms indicating tardive dyskinesia, the advisability of discontinuing all antipsychotic drugs, including Risperidone, should be considered.
Neuroleptic malignant syndrome.
In case of development of neuroleptic malignant syndrome, characterized by hyperthermia, muscle rigidity, instability of the function of the autonomic nervous system, disturbances of consciousness and increased activity of creatine phosphokinase in the blood serum (myoglobinuria (rhabdomyolysis) and acute renal failure may also be observed), it is necessary to discontinue all antipsychotic drugs, including risperidone .
Leukopenia, neutropenia and agranulocytosis
Cases of leukopenia, neutropenia and agranulocytosis have been observed with the use of antipsychotics, including risperidone. Agranulocytosis was very rare (less than 1/10,000 patients) in post-marketing surveillance. Patients with a clinically significant decrease in the number of white blood cells or with drug-induced leukopenia/neutropenia should be observed during the first few months of treatment. At the first sign of a decrease in the number of blood leukocytes (in the absence of other reasons), discontinuation of risperidone should be considered. Patients with a clinically significant decrease in white blood cell count should be monitored for possible fever or other signs of infection. Patients with severe neutropenia (absolute neutrophil count less than 1 x 109) require discontinuation of risperidone and observation until neutrophil counts return to normal.
Parkinson's disease or dementia with Lewy bodies.
Antipsychotic medications, including risperidone, should be prescribed with caution to patients with Parkinson's disease or dementia with Lewy bodies. Both groups of patients have an increased risk of developing neuroleptic malignant syndrome and increased sensitivity to antipsychotic drugs (including dullness of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms). Parkinson's disease may worsen when taking risperidone.
Intraoperative tremulous iris syndrome
This syndrome has been observed during cataract surgery in patients receiving drugs that are antagonists of force-adrenergic receptors. Shaky iris syndrome may increase the risk of eye complications during and after eye surgery. The operating ophthalmologist should be informed that the patient is taking a1A-adrenergic receptor antagonists. The use of α1A-blockers before cataract surgery in patients receiving α1-adrenergic antagonists has not been studied.
Antiemetic effect
An antiemetic effect was observed in preclinical studies of risperidone. This effect in humans may mask the signs and symptoms of overdose of certain drugs, as well as symptoms of such conditions as intestinal obstruction, hepatocerebral syndrome, or brain tumor.
Hyperglycemia, diabetes mellitus.
Hyperglycemia, diabetes mellitus, or exacerbation of existing diabetes mellitus have been observed during treatment with risperidone. It is likely that weight gain prior to treatment is also a predisposing factor. Very rarely, ketoacidosis and rarely, diabetic coma can occur. All patients should be clinically monitored for symptoms of hyperglycemia (polydipsia, polyuria, polyphagia and weakness) and diabetes mellitus. All patients with diabetes should be regularly monitored for worsening glucose control.
Increase in body weight.
Significant weight gain was observed with risperidone treatment. During risperidone therapy, it is necessary to monitor patients' body weight.
Hyperprolactinemia
Based on the results of tissue culture studies, it has been suggested that the growth of breast tumor cells may be stimulated by prolactin. Although clinical and epidemiological studies have not shown a clear association between hyperprolactinemia and antipsychotic drug use, caution should be exercised when prescribing risperidone to patients with a history of this. Caution is recommended when used in patients with hyperprolactinemia (including a history) or risk of developing prolactin-dependent tumors, since risperidone may increase the concentration of prolactin in the blood.
Extending the interval
QT.
Prolongation of the QT interval has been very rarely observed in the post-marketing period. As with other antipsychotics, caution should be exercised when prescribing risperidone to patients with known cardiovascular disease, a family history of QT prolongation, bradycardia, or electrolyte imbalance (hypokalemia, hypomagnesemia) as this may increase the risk of arrhythmogenic effects; and when used simultaneously with drugs that increase the QT interval.
Convulsions
The ability of typical antipsychotics to lower the seizure threshold is known, so risperidone should be prescribed with caution to patients with epilepsy.
Priapism
Due to the blockade of α-adrenergic receptors, risperidone can cause priapism.
Violation of thermoregulation
Antipsychotic drugs may cause problems with body temperature regulation. Caution should be exercised when prescribing Risperidone to patients with conditions that may contribute to an increase in body temperature, such as intense physical activity, dehydration, exposure to high temperatures, or concomitantly using drugs with anticholinergic activity.
Venous thromboembolism
Cases of venous thromboembolism have been reported with the use of antipsychotic drugs. Since patients taking antipsychotic drugs are often at risk of developing venous thromboembolism, all possible risk factors should be identified before and during treatment with risperidone, and preventive measures should be taken.
Children and teenagers
Before prescribing Risperidone to children or children with retardation, their condition should be carefully assessed for the presence of physical or social causes of aggressive behavior, such as pain or inadequate demands of the social environment. The sedative effect of risperidone should be carefully monitored in this population due to the possible effect on learning ability. Changing the timing of drug administration may improve control of the effects of sedation on attention in adolescents and children. Risperidone use was associated with mean increases in body weight and body mass index. Height changes in long-term studies were within expected age-specific norms. The effect of long-term use of risperidone on sexual development and growth has not been fully studied. Due to the possible impact of prolonged hyperprolactinemia on growth and sexual development in children and adolescents, regular clinical assessment of hormonal status should be carried out, including measurement of height, weight, monitoring of sexual development, menstrual cycle and other possible prolactin-dependent effects. During treatment with risperidone, regular assessment for the presence of extrapyramidal symptoms and other movement disorders should be carried out.
Side effects
The drug is usually well tolerated. According to clinic doctors, it is one of the well-tolerated antipsychotics. In approximately 10% of cases, the following side effects are possible.
- Increased muscle tone, restlessness, trembling, feeling of stiffness, “extrapyramidal syndrome,” parkinsonism. To prevent these phenomena, correctors may be additionally prescribed: trihexyphenidyl (Cyclodol), biperiden (Akineton, Mendylex, Bezac), amantadine (PK-Merz), etc.
- Headache.
- Insomnia.
Rare but unpleasant side effects include metabolic (metabolic) disorders: weight gain and the development of diabetes. As a rule, such effects develop in persons predisposed to this.
Therefore, to avoid them, it is recommended to conduct an examination with blood tests before starting therapy to exclude an increase in glucose and prolactin in the blood.
