RISPOLENT (RISPORIDONE) - AN ATYPICAL HIGHLY EFFECTIVE NEUROLEPTIC

Pharmacological properties of the drug Risperidone

Neuroleptic. A selective antagonist of 5-HT2-serotonergic and D2-dopaminergic receptors in the central nervous system, it also blocks α1-adrenergic and, to a lesser extent, H1-histamine and α2-adrenergic receptors; has no effect on cholinergic receptors. Has an antipsychotic effect (eliminates delusions, hallucinations, automatism). Reduces feelings of fear, reduces aggressiveness. To a lesser extent than classical neuroleptics, it inhibits motor activity and inhibits catalepsy. Risperidone is completely absorbed after oral administration. The maximum concentration in blood plasma is achieved after 1–2 hours, the volume of distribution is 1–2 l/kg. The binding of risperidone to plasma proteins (albumin and α1-acid glycoprotein) is 88%. Partially metabolized to form 9-hydroxy-risperidone, which has pharmacological activity similar to risperidone and binds to plasma proteins by 77%. A steady-state level of risperidone plasma concentration in most patients is achieved within 1 day, 9-hydroxyrisperidone within 4–5 days. 1 week after administration, 70% of the dose taken is excreted in urine and 14% in feces. The total content of risperidone and 9-hydroxy-risperidone in the urine is 35–45% of the dose, the rest being pharmacologically inactive metabolites. The half-life of risperidone is about 3 hours, 9-hydroxyrisperidone - 24 hours. In elderly patients, as well as with severe renal impairment, after a single dose, higher concentrations of the active substance and slower elimination are observed. In patients with severely impaired liver function, the concentration of risperidone in the blood plasma does not differ from those observed in patients with normal liver function.

Drug interactions

With the simultaneous use of inducers of microsomal liver enzymes, a decrease in the concentration of risperidone in the blood plasma is possible.

When used simultaneously with phenothiazine derivatives, tricyclic antidepressants and beta-blockers, the concentration of risperidone in the blood plasma may increase [14].

When used simultaneously with carbamazepine, the concentration of risperidone in the blood plasma is significantly reduced.

When used concomitantly, risperidone reduces the effects of levodopa and other dopamine receptor agonists[14]. Potentiates the effect of neuroleptics[6].

When used simultaneously with fluoxetine, an increase in the concentration of risperidone in the blood plasma is possible.

Use of the drug Risperidone

Adults are prescribed an initial dose of 2 mg/day. The next day, increase the dose to 4 mg/day, and on the 3rd day of treatment - to 6 mg/day in 1 or 2 doses. In the future, a maintenance dose is selected individually, usually 4–8 mg/day. The maximum daily dose is 16 mg. In elderly patients or in patients with severe impairment of liver and/or kidney function, the initial and subsequent doses are halved. In case of transition from therapy with other antipsychotic drugs to the use of risperidone, it is recommended to discontinue these drugs if possible.

Release form

One of the advantages of this drug is the presence of all the dosage forms necessary for psychiatrists: tablets, drops, extended-release injections (depot).
Pills

2 or 4 milligrams per package of 10,20,30,50,60 or 100 pieces

Drops

. In bottles of 30 or 100 milliliters. A special graduated pipette is included, which is used to determine the amount of a single dose to take.

Depot

. In powder form for the preparation of a long-acting intramuscular suspension. Dosages: 25, 37.5 and 50 milligrams. It is used as an intramuscular injection, which will ensure slow release and entry of the drug into the blood over 2 - 3 weeks. Produced under the name RISPOLEPT CONST.

Side effects of the drug Risperidone

Often - insomnia, increased excitability, anxiety, headache; possible drowsiness, fatigue, dizziness, impaired concentration; in some cases - extrapyramidal disorders (tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia), neuroleptic syndrome, tardive dyskinesia, thermoregulation disorders, epileptic seizures; blurred vision; possible constipation, nausea, vomiting, abdominal pain, increased activity of liver enzymes; orthostatic hypotension, tachycardia, hypertension (arterial hypertension), edema; priapism, erectile dysfunction, ejaculation and orgasm, urinary incontinence; a dose-dependent increase in the concentration of prolactin in the blood plasma, accompanied by galactorrhea, gynecomastia, menstrual irregularities and amenorrhea; syndrome of inappropriate secretion of antidiuretic hormone; weight gain, polydipsia; neutropenia, thrombocytopenia; rhinitis, allergic reactions.

Notes

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3. Kirino E. (2014). "Efficacy and tolerance of pharmacotherapy options for the treatment of irritability in autistic children." Clin Med Insights Pediatr 8
   : 17–30. DOI:10.4137/CMPed.S8304. PMID 24932108.
4. FDA (October 2, 2006). FDA Approves the First Drug to Treat Irritability Associated with Autism, Risperdal. Press release. — Press release from the FDA, USA. (English)
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6. ↑ 1 2 Podkorytov V.S., Chaika Yu.Yu.
   Depression. Modern therapy. - Kharkov: Tornado, 2003. - 352 p. — ISBN 966-635-495-0.
7. ↑ 1 2 3 4
   Clinical psychiatry: [Text.
   manual]: Transl. from English, revised and additional / H.I. Kaplan, B.J. Zadok; Ed. and ed. add. Yu.A. Alexandrovsky, A.S. Avedisova, L.M. Bardenstein et al.; Ch. ed.: T.B. Dmitrieva. - Moscow: GEOTAR MEDICINE, 1998. - 505 p. — ISBN 5-88816-010-5. Original:
   Pocket Handbook of Clinical Psychiatry / Harold I Kaplan, Benjamin J Sadock. - Baltimore: Williams & Wilkins. — ISBN 0-683-04583-0.
8. Risk of developing extrapyramidal syndrome in patients with schizophrenia receiving antipsychotics: a population study // Clin. Pharmacol. Ther.. - 2007.
9. Tarsy D, Lungu C, Baldessarini RJ.
   Epidemiology of tardive dyskinesia before and during the era of modern antipsychotic drugs // Handb Clin Neurol. - 2011. - T. 100. - P. 601-16. - PMID 21496610.
10. Yavorskaya S.A.
    The use of selective serotonin reuptake inhibitors in neurological practice // Russian Medical Journal. - March 7, 2007 - No. 5.
11. Park CH, Park TW, Yang JC, Lee KH, Huang GB, Tong Z., Park MS, Chung YC
    No negative symptoms in healthy volunteers after single doses of amisulpride, aripiprazole, and haloperidol: a double-blind placebo-controlled trial. (English) // International clinical psychopharmacology. - 2012. - Vol. 27, no. 2. - P. 114-120. — DOI:10.1097/YIC.0b013e3283502773. - PMID 22241281.
12. Pharmacotherapy in neurology and psychiatry: [Trans. from English] / Ed. S. D. Enna and J. T. Coyle. - Moscow: LLC: "Medical Information Agency", 2007. - 800 pp.: ill. With. — 4000 copies. — ISBN 5-89481-501-0.
13. Burbello A.T., Babak S.V., Andreev B.V., Kolbin A.S., Goryachkina K.A.
    Adverse adverse reactions of drugs (a manual for doctors) / Ed. A.T.Burbello. - St. Petersburg, 2008. Archived on December 24, 2014.
14. ↑ 1 2 3 4 5 6 Gubsky Yu. I., Shapovalova V. A., Kutko I. I., Shapovalov V. V.
    Medicines in psychopharmacology. - Kyiv - Kharkov: Health - Torsing, 1997. - 288 p. — 20,000 copies. — ISBN 5-311-00922-5, 966-7300-04-8.
15. ↑ 1 2 Burchinsky S.G.
    The problem of safety in the strategy of pharmacotherapy with atypical neuroleptics // Neuro News: psychoneurology and neuropsychiatry. — September 2010. — No. 5 (24). Archived from the original on October 6, 2014.
16. ↑ 1 2 3 Gorobets L.N., Bulanov V.S., Komissarov P.S., Ermolaeva L.G.
    The problem of hyperprolactinemia during therapy with antipsychotic drugs // Social and clinical psychiatry: journal. - 2003. - T. 13, issue. 1. - pp. 164–169. — ISSN 0869-4893.
17. ↑ 1 2 3 4 Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, Kreyenbuhl J.
    Practice Guideline for the Treatment of Patients With Schizophrenia. — 2nd ed. — American Psychiatric Association, 2004. Translation of the fragment: The use of antipsychotics in schizophrenia // Standards of world medicine. - 2005. - No. 2/3. — P. 83-112. Archived from the original on September 25, 2013.
18. ↑ 1 2 3 4 Kushnir O.N.
    Hyperprolactinemia in psychiatric practice (clinical picture, treatment, prevention) // Psychiatry and psychopharmacotherapy. - 2007. - T. 9, No. 1. Archived on February 2, 2013.
19. Maguire GA.
    Increased prolactin levels during antipsychotic therapy: mechanisms of action and clinical implications (abstract) =
    J Clin Psychiatry
    2002;
    63
    (suppl. 4): 56–62 // Psychiatry and psychopharmacology. - 2006. - T. 08, No. 6. (inaccessible link)
20. Gorobets L.N., Polyakovskaya T.P., Litvinov A.V.
    and others. The problem of osteoporosis in patients with mental disorders. Part 2 // Social and clinical psychiatry. - 2013. - T. 23, No. 1. - P. 87-92.
21. Szarfman A, Tonning JM, Levine JG, Doraiswamy PM (June 2006). "Atypical antipsychotics and pituitary tumors: a pharmacovigilance study." Pharmacotherapy 26
    (6):748–58. DOI:10.1592/phco.26.6.748. PMID 16716128. (inaccessible link) Translation: Atypical antipsychotics and pituitary tumors: a pharmacovigilance study
22. Tsygankov B.D., Agasaryan E.G.
    Modern and classical antipsychotic drugs: comparative analysis of effectiveness and safety // Psychiatry and psychopharmacotherapy. - 2006. - T. 8, No. 6. Archived on February 2, 2013.
23. Grigorieva E.A., Ritskov A.S.
    Features of the action of the atypical neuroleptic amisulpride // Journal of Neurology and Psychiatry named after. S.S. Korsakov. - 2004. - No. 6. Archived on October 6, 2014.
24. Gorobets L.N., Polyakovskaya T.P., Litvinov A.V.
    and others. The problem of osteoporosis in patients with mental disorders. Part 1 // Social and clinical psychiatry. - 2012. - T. 22, No. 3. - P. 107-112.
25. Peuskens J, Pani L, Detraux J, De Hert M.
    The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review // CNS Drugs. — 2014 May. - Vol. 28, no. 5. - P. 421-53. — DOI:10.1007/s40263-014-0157-3. - PMID 24677189.
26. Rational pharmacotherapy in psychiatric practice: a guide for practitioners / Ed. ed. Yu. A. Alexandrovsky, N. G. Neznanov. - Moscow: Litterra, 2014. - 1080 p. — (Rational pharmacotherapy). — ISBN 978-5-4235-0134-1.
27. Malyarov S. A.;
    preparation M. Dobryanskaya. Adverse reactions of antipsychotic drugs // Neuro News: psychoneurology and neuropsychiatry. — January 2010. — No. 1 (20).
28. Chabroux S, Haffen E, Penfornis A.
    Diabetes and second-generation (atypical) antipsychotics // Ann Endocrinol (Paris). — 2009 Sep. - T. 70, No. 4. - P. 202-10. — DOI:10.1016/j.ando.2009.07.003. - PMID 19700142.
29. ↑ 1 2 3 Melkersson K, Dahl ML.
    Metabolic disorders during therapy with atypical antipsychotics (abstract) // Psychiatry and psychopharmacotherapy. - 2006. - T. 11, No. 2. Archived on January 19, 2013.
30. ↑ 1 2 3 Mosolov S.N., Ryvkin P.V., Serditov O.V., Ladyzhensky M.Ya., Potapov A.V.
    Metabolic side effects of modern antipsychotic pharmacotherapy // Social and clinical psychiatry. - Moscow, 2008. - T. 18, issue. 3. - pp. 75-90.
31. ↑ 123
    Psychiatry. National leadership / Ed. Dmitrieva T.B., Krasnova V.N., Neznanova N.G., Semke V.Ya., Tiganova A.S. — Moscow: GEOTAR-Media, 2011.
32. Malyarov S. A.;
    preparation M. Dobryanskaya. Adverse reactions of antipsychotic drugs // Neuro News: psychoneurology and neuropsychiatry. — January 2010. — No. 1 (20). (unavailable link)
33. Gorobets L.N.
    Endocrine side effects of neuroleptic therapy. — All-Russian public organization of people with disabilities due to mental disorders and their families “New Opportunities.” IV interregional meeting. April 17-20. Moscow, 2005. Archived on February 22, 2012.
34. ↑ 1 2 P. Goetsche.
    Deadly drugs and organized crime: How Big Pharma corrupted healthcare / [Trans. from English L. E. Ziganshina]. - Moscow: Publishing House "E", 2021. - 464 p. — (Evidence-based medicine). — 3000 copies. — ISBN 978-5-699-83580-5.

Special instructions for the use of the drug Risperidone

Use with caution in patients with diseases of the cardiovascular system, dehydration, hypovolemia, cerebrovascular disorders; The dose of risperidone in such patients is increased gradually. Prescribe with caution to patients with epilepsy, Parkinson's disease and in case of simultaneous use of other drugs that have an effect on the central nervous system. If tardive dyskinesia occurs, discontinuation of risperidone should be considered. In case of development of malignant neuroleptic syndrome (hyperthermia, muscle rigidity, disturbances of consciousness, increased CPK levels), the drug is discontinued. Patients taking risperidone are advised to avoid overeating due to possible weight gain. During treatment, it is not recommended to perform work that requires increased attention and speed of motor and mental reactions (including driving), until individual sensitivity to risperidone is determined. During pregnancy, it is used only when the expected benefit to the woman outweighs the potential risk to the fetus. If it is necessary to prescribe risperidone during breastfeeding, the issue of stopping breastfeeding should be decided. There is no clinical experience with the use of risperidone in children.

Criticism

In 2012, according to a court decision in the United States, Johnson & Johnson, which produces Risperdal (risperidone), was fined more than $1.1 billion. The jury found that the company and its Janssen subsidiary downplayed and concealed risks associated with the drug, such as increased risks of mortality, strokes, seizures, weight gain and diabetes. A panel of federal drug experts concluded that the drug was overused. More than a quarter of the patients who took this drug, including those without a prescription, were children and adolescents. World-renowned child psychiatrist Joseph Biederman of Harvard actively promoted Risperdal for use in children and extorted money from the company.[34]

In April 2012, the US government pursued another Johnson & Johnson fraud case in which the company paid bribes to Omnicare, the nation's largest nursing home pharmacy, to force it to purchase and recommend Risperdal and other company drugs. However, Johnson & Johnson concealed from Omnicare that the FDA had prohibited advertising of Risperdal as an effective and safe drug for elderly patients because it had not been adequately studied, and that it had not approved the drug for the treatment of psychotic and behavioral manifestations of dementia (the most common use in clinics operated by Omnicare) due to a lack of safety data[34].

Links

• Risperidone //MedLinePlus
• Risperidone: Pharmacopoeial monograph
• Risperidone synthesis scheme