Risperidone

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Structural formula
Risperidone Structural Formulas V.1.svg
General
Non-proprietary name Risperidone
other names
  • 3- {2- [4- (6-fluoro-1,2-benzisoxazol-3-yl) piperidino] ethyl} -2-methyl-6,7,8,9-tetrahydro-4 H -pyrido [1,2- - a ] pyrimidin-4-one ( IUPAC )
  • Risperidonum ( Latin )
Molecular formula C 23 H 27 FN 4 O 2
Brief description

white to almost white, polymorphic powder

External identifiers / databases
CAS number 106266-06-2
EC number 600-733-1
ECHA InfoCard 100.114.705
PubChem 5073
DrugBank DB00734
Wikidata Q412443
Drug information
ATC code

N05 AX08

Drug class

atypical neuroleptics

properties
Molar mass 410.48 g · mol -1
Physical state

firmly

Melting point

170 ° C

solubility

practically insoluble in water, slightly soluble in dichloromethane , slightly soluble in ethanol

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
06 - Toxic or very toxic

danger

H and P phrases H: 301
P: 301 + 310
Toxicological data

56.6 mg kg −1 ( LD 50ratoral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Risperidone is a drug from the group of neuroleptics that are primarily used in psychiatry to treat schizophrenia . Risperidone is often referred to as an atypical neuroleptic because the side effects on the extrapyramidal motor system are said to be less than with classic first-generation neuroleptics. There are studies that seem to support this, but there are also studies that do not. It has been on the WHO Essential Medicines List since 2013 .

power

The neuroleptic potency of risperidone is stated to be about 50 times that of chlorpromazine . The active ingredient is therefore one of the highly potent neuroleptics , comparable to flupentixol , fluspiril or olanzapine .

Chemical structure

Risperidone is a benzisoxazole derivative and structurally related to ziprasidone , in a broader sense also to aripiprazole .

Pharmacodynamics

Probably much responsible for the antipsychotic effect of risperidone D 2 - Affinity is about 1/3 that of haloperidol . The 5-HT 2 - antagonism is at risperidone 20-fold more pronounced than the effect on dopamine receptors , which has consequences for the psychotic negative symptoms but also for side effects in combination therapy has. Risperidone also acts as an antagonist on adrenoceptors (causes blood pressure lowering) and histamine H 1 receptors (dry mouth, tiredness). Like metitepine, risperidone and the 9-OH metabolite paliperidone deactivate the 5-HT 7 receptor in a pseudo- reversible binding manner without internalization being observed. This could explain cerebrovascular side effects.

Pharmacokinetics

Risperidone has a half-life of 2-4 hours. The half-life for the active metabolite 9-hydroxy- risperidone is 17–23 hours.

unwanted effects

Risperidone leads to disorders of the extrapyramidal motor system (EPMS) less often than the "classic" substances ( butyrophenones or phenothiazines ). However, the EPMS-triggering effect is not zero. B. be comparable to that of Flupentixol . Risperidone also has other interfering effects that can be detrimental to compliance , such as weight gain or an increase in serum prolactin levels . Overall, it is hardly sedating . Occasionally, amenorrhea , erectile dysfunction, ejaculation disorders, gynecomastia, or menstrual disorders can occur.

Combination therapy with risperidone and other psychotropic drugs ( see below ) tends to increase the incidence and extent of undesirable effects. The combination with diuretics such as furosemide is particularly risky in elderly patients.

In September 2013, the manufacturer of the original preparation (pointed Janssen-Cilag , Risperdal) in a Red Hand Letter to the risk of intraoperative floppy iris syndrome (IFIS) in conjunction with a treatment with risperidone or paliperidone in patients who undergo cataract (cataract) surgery.

Indications

Risperidone is approved for the therapy of severe and chronic schizophrenia-like and schizoaffective disorders , for the treatment of manic phases and for the short-term treatment (up to six weeks) of long-term aggression in two target groups: firstly, in people with Alzheimer's dementia who are harmful to themselves and others after exhausting other therapeutic options, and secondly for mentally disabled children from at least five years and adolescents with behavioral disorders . It has no proven phase prophylactic effect. It is also used for obsessive-compulsive disorders and severe personality disorders. In post-traumatic stress disorder , risperidone may have the potential to reduce intrusions and irritability.

There is also evidence of efficacy in the context of augmentation for the treatment of major depressions that did not respond or only inadequately to monotherapy (e.g. with SSRIs).

Contraindications

Hyperprolactinemia excludes the use of risperidone unless it is drug-related (i.e. reversible by discontinuation of the causative drug).

Conditions in which risperidone should only be administered with particular caution include QT interval prolongation in the ECG (certain heart diseases ), as the substance has a potentially QT-prolonging effect. In dementia , use is contraindicated if Parkinson’s symptoms ( rigor , bradykinesia and Parkinson’s postural disorders) or the probable diagnosis of Lewy body dementia are present. An American study with older patients showed that the risk of cerebrovascular events ( TIA , cerebral infarction ) increases significantly compared to the application of a placebo preparation .

Combination therapy

Risperidone is sometimes used in combination with other pharmaceuticals to treat mental disorders other than schizophrenia and mania ( augmentation ).

  • Bipolar disorder . There are no reliable study results that prove a benefit from risperidone, with the exception of the acute manic phase.
  • Depression . There is no reliable proof of benefits, but recommendations from manufacturers close to the source and individual case reports with positive results. Simultaneous administration of risperidone and SSRIs increases the risk of serotonin syndrome and should only be used with caution. The combination of risperidone and paroxetine can lead to very severe weight gain.
  • Schizophrenia: A study of the combination of clozapine / risperidone showed no improved efficacy compared to the individual substances.
  • in ADHD as a comorbidity with autism , or with severe social behavior disorders or aggressiveness.

Other Information

After Risperdal was introduced in 1994, the term atypical neuroleptic (atypicals) became popular.

Risperidone was the most frequently prescribed atypical neuroleptic in Germany in 2009 with 29.0 million daily doses (DDD) after quetiapine (33.3 million daily doses). This is an increase of 14.9% over 2008. In 2007 , the risperidone-containing preparation Risperdal ® took first place among the drugs with the highest sales in Germany . The active ingredient risperidone is offered in various dosage forms. A preparation for parenteral use with delayed release has been available under the name Risperdal CONSTA ® - the first atypical depot neuroleptic . Alternatively, patients risperidone in the form of a tablet , a dispersible tablet , a solution , and since October 2010, also in the form of a melt film consume.

In November 2013, Johnson & Johnson reached a settlement that paid $ 2.2 billion to the US government because the Risperdal drug was illegally advertised and marketed. In December 2016, 13,000 men filed class actions against Johnson & Johnson in the United States. They developed gynecomastia (men's breasts) as a side effect of the drug Risperdal . In October 2019, a Philadelphia jury awarded a plaintiff over $ 8 billion in punitive damages . Johnson & Johnson has announced that it will challenge the verdict .

Trade names

Monopreparations

Risperdal (D, A, CH), as intramuscular depot form Risperdal-Consta (D, A, CH), numerous generics (D, A, CH): e.g. B. Aleptan (A), Risocon (D), RispeCare (D), Rispe-Q (D), Risperigamma (D), Risperihex (A), Risperipharm (A).

See also

literature

  • RD Rattehalli, S. Zhao, BG Li, MB Jayaram, J. Xia, S. Sampson: Risperidone versus placebo for schizophrenia. In: The Cochrane database of systematic reviews. Volume 12, 12 2016, p. CD006918, doi: 10.1002 / 14651858.CD006918.pub3 , PMID 27977041 (Review).
  • M. Corena-McLeod: Comparative Pharmacology of Risperidone and Paliperidone. In: Drugs in R&D. Volume 15, number 2, June 2015, pp. 163-174, doi: 10.1007 / s40268-015-0092-x , PMID 25943458 , PMC 4488186 (free full text) (review).
  • RH Hunter et al. a .: Risperidone versus typical antipsychotic medication for schizophrenia. In: The COCHRANE database of Systematic Reviews. 2005, Issue 4. PMID 12804396 .
  • HJ. Möller, WE Müller, B. Bandelow: Neuroleptics, Pharmacological Basics, Clinical Knowledge and Therapeutic Approach. Stuttgart 2001, ISBN 3-8047-1773-X .
  • M. Jüptner, MT Gastpar: Deaths taking risperidone and olanzapine - what now? Treatment of psychotic symptoms in dementia patients. In: psychoneuro. 30, 2004, pp. 314–316, doi: 10.1055 / s-2004-829992 ( conflict of interest : Prof. Gastpar had financial connections with the manufacturer of Risperdal®).

Web links

Commons : Risperidone  - Collection of Images, Videos and Audio Files

Individual evidence

  1. a b European Pharmacopoeia Commission (Ed.): European Pharmacopoeia . 5th edition edition. tape 5.0-5.8 , 2006.
  2. a b Entry on risperidone in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  3. a b Risperidone data sheet from Sigma-Aldrich , accessed on April 22, 2011 ( PDF ).
  4. JG Csernansky et al. a .: A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. In: New England Journal of Medicine . 346 (1), Jan 3, 2002, pp. 16-22. PMID 11777998 .
  5. ^ JA Lieberman et al.: Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. In: New England Journal of Medicine. 353 (12), Sep 22, 2005, pp. 1209-1223. PMID 16172203 .
  6. A. Schotte, PFM Janssen, W. Gommeren: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. In: Psychpharmacol. 124, 1996, pp. 57-73. PMID 8935801 .
  7. M. Teitler, N. Toohey, JA Knight, MT Klein, C. Smith: Clozapine and other competitive antagonists reactivate risperidone-inactivated h5-HT7 receptors: radioligand binding and functional evidence for GPCR homodimer protomer interactions. In: Psychopharmacology. Volume 212, number 4, December 2010, pp. 687-697, doi: 10.1007 / s00213-010-2001-x , PMID 20827463 , PMC 3052287 (free full text).
  8. C. Smith et al. a .: Risperidone Irreversibly Binds to and Inactivates the h5-HT7 Serotonin Receptor. In: Mol Pharmacol . 70, 2006, pp. 1264-1270.
  9. Otto Benkert, Hanns Hippius: Compendium of Psychiatric Pharmacotherapy . Ed .: Hanns Hippius. 12th edition. Springer, Berlin, ISBN 978-3-662-57333-4 .
  10. Frequency of rigor with flupentixol decanoate and risperidone depending on the dosage. In: Psychiatr Prax. 31 Suppl 1, Nov 2004, pp. 167-169. PMID 15570542 .
  11. ^ Frank Schneider: Clinic manual for psychiatry, psychosomatic medicine and psychotherapy. Springer Verlag, 2008, ISBN 978-3-540-78466-1 , p. 118.
  12. a b Technical information Risperidon-Mepha Lactab / solution Risperidon-Mepha oro orodispersible tablets at Compendium.ch, accessed on May 8, 2014.
  13. Source: Technical information on Risperdal (R) as of December 2006.
  14. Rote-Hand-Brief from Janssen-Cilag on September 9, 2013. (PDF; 397 kB) Accessed on September 10, 2013 .
  15. Swiss Society for obsessive-compulsive disorder - Drug treatment of obsessive-compulsive disorder .
  16. Hans-Bernd Rothenhäusler, Karl-Ludwig Täschner: Compendium of practical psychiatry . Springer-Verlag, Vienna 2007. ISBN 978-3-211-48641-2 . P. 122.
  17. Edward P. Monnelly, Domenic A. Ciraulo, Clifford Knapp, Terence Keane: Low-Dose Risperidone as Adjunctive Therapy for Irritable aggression in Post Traumatic Stress Disorder. In: Journal of Clinical Psychopharmacology . 23, April 2003, pp. 193-196. (Abstract)
  18. Benkert, O., 1940-, Hippius, Hanns ,: Compendium of Psychiatric Pharmacotherapy . 12th, completely revised and updated edition. Berlin, Germany 2019, ISBN 978-3-662-57334-1 .
  19. Eric Wooltorton: Risperidone (Risperdal): increased rate of cerebrovascular events in dementia trials. In: CMAJ. vol. 167 no. 11, Nov 26, 2002, pp. 1269-1270.
  20. ( Page no longer available , search in web archives: Treatment-Resistant Bipolar Depression: A STEP-BD Equipoise Randomized Effectiveness Trial of Antidepressant Augmentation With Lamotrigine, Inositol, or Risperidone. ) In: Am J Psychiatry. 163 (2), Feb 2006, pp. 210-216. PMID 16449473 .@1@ 2Template: Dead Link / psychiatryonline.org
  21. Two active ingredients break through the depression together: paroxetine plus risperidone in case of therapy resistance ( Memento of July 13, 2006 in the Internet Archive ) (manufacturer-sponsored article in the Ärzte Zeitung ).
  22. H. Fukui, T. Murai: Severe Weight Gain Induced by Combination Treatment With Risperidone and Paroxetine. In: Clin Neuropharmacol . 25, 2002, pp. 269-271. PMID 12410060 .
  23. ^ WG Honer, AE Thornton, EY Chen, RC Chan, JO Wong, A. Bergmann, P. Falkai, E. Pomarol-Clotet, PJ McKenna, E. Stip, R. Williams, GW MacEwan, K. Wasan, R. Procyshyn; Clozapine and Risperidone Enhancement (CARE) Study Group: Clozapine Alone versus Clozapine and Risperidone with Refractory Schizophrenia. In: New England Journal of Medicine. 354 (5), Feb 2, 2006, pp. 472-482. PMID 16452559 .
  24. Christine M. Freitag, Wolfgang Retz: ADHD and comorbid diseases: neurobiological principles and diagnostic-therapeutic practice in children and adults . W. Kohlhammer Verlag, 2007, ISBN 978-3-17-019081-8 , p. 81.
  25. Ulrich Schwabe, Dieter Paffrath (Ed.): Drug Ordinance Report 2010 . Springer, Berlin 2010, ISBN 978-3-642-13379-4 , pp. 826 .
  26. Ulrich Schwabe, Dieter Paffrath (ed.): Drug Ordinance Report 2008 . Springer, Berlin 2008, ISBN 978-3-540-69218-8 , pp. 12 . ; springer.com (PDF; 895 kB) accessed on January 15, 2011.
  27. ^ Attorney General Eric Holder Delivers Remarks at the Johnson & Johnson Press Conference .
  28. Waltraud Messmann: 13,000 men grew breasts after taking medication .
  29. Schizophrenia Drug - Growing Male Breasts: Billion ruling against pharmaceutical company. In: srf.ch . October 9, 2019, accessed October 9, 2019 .
  30. Red List Online, as of August 2009.
  31. AM comp. d. Switzerland, as of August 2009.
  32. AGES-PharmMed, as of August 2009.
  33. HJ Möller u. a .: Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German Research Network on Schizophrenia. In: Int J Neuropsychopharmacol . 11 (7), 2008, pp. 985-997. PMID 18466670 .