employee
VAK Russia 3.1.24
UDC 616
This long-term clinical observation presents a patient with continuous paranoid schizophrenia manifesting as paraphrenic syndrome. A reduction of psychotic symptoms was achieved with a combination of high-dose clozapine (600 mg/day) and haloperidol (60 mg/day) in combination with bromdihydrochlorophenylbenzodiazepine (1 mg/day) as concomitant therapy. This case demonstrates the possibility of partially overcoming treatment resistance through such therapy and its reasonably good individual tolerability.
continuous paranoid schizophrenia, paraphrenic syndrome, therapeutic resistance, combination antipsychotic therapy, clozapine, haloperidol, high-dose antipsychotics, typical antipsychotics, atypical antipsychotics, concomitant therapy, bromdihydrochlorophenylbenzodiazepine
1. Danilov D.S. Terapevticheskaya rezistentnost' pri shizofrenii i biologicheskie metody ee preodoleniya. Zhurnal nevrologii i psihiatrii im. S.S.Korsakova. 2008;108(10):81-86.
2. Danilov D.S. Kupiruyuschaya terapiya obostreniy nepreryvnoy paranoidnoy shizofrenii (effektivnost' klozapina, risperidona, olanzapina, kvetiapina i tipichnyh neyroleptikov i ee zavisimost' ot klinicheskih osobennostey zabolevaniya). Sibirskiy vestnik psihiatrii i narkologii. 2010;3(60):82-88.
3. Danilov D.S., Morozova V.D. Optimizaciya lechebnogo processa u bol'nyh shizofreniey, rezistentnyh k antipsihoticheskoy terapii. Rossiyskiy psihiatricheskiy zhurnal. 2010;(4):75-83.
4. Malin D.I. Sovremennyy vzglyad na effektivnost' elektrosudorozhnoy terapii v lechenii bol'nyh shizofreniey. Sovremennaya terapiya psihicheskih rasstroystv. 2024;(2):14-21.
5. Mosolov S.N., Cukarzi E.E., Oleneva E.V., Alfimov P.V. Sovremennye metody preodoleniya terapevticheskoy rezistentnosti pri shizofrenii. V kn.: Mosolov S.N., redaktor. Biologicheskie metody terapii psihicheskih rasstroystv. Dokazatel'naya medicina – klinicheskoy praktike. Moskva: Social'no-politicheskaya mysl'; 2012. S. 102-117.
6. Barber S., Olotu U., Corsi M., Cipriani A. Clozapine combined with different antipsychotic drugs for treatment-resistant schizophrenia. Cochrane Database Syst Rev. 2017 Mar;3(3): CD006324. doi:https://doi.org/10.1002/14651858.CD006324.pub3
7. Samara M., Alevizopoulos G., Bozikas V.P., et al. Current perspectives on the recognition and management of treatment-resistant schizophrenia: challenges and opportunities. Expert Rev Neurother. 2025 Mar;25(5):505-19. doi:https://doi.org/10.1080/14737175.2025.2484434
8. Schneider-Thoma J., Hamza T., Chalkou K., et al. Efficacy of clozapine versus second-generation antipsychotics in people with treatment-resistant schizophrenia: a systematic review and individual patient data meta-analysis. Lancet Psychiatry. 2025 Apr;12(4):254-65. doi:https://doi.org/10.1016/S2215-0366(25)00001-X
9. Sinclair D.J., Zhao S., Qi F., et al. Electroconvulsive therapy for treatment-resistant schizophrenia. Cochrane Database Syst Rev.2019 Mar;3(3):CD011847. doi:https://doi.org/10.1002/14651858.CD011847.pub2
10. Wagner E., Borgwardt S., Hasan A. Management of treatment-resistant schizophrenia (article in German). Nervenarzt. 2024 May;95(5):423-31. doi:https://doi.org/10.1007/s00115-024-01608-6
11. Danilov D.S. Terapiya shizofrenii (atipichnye neyroleptiki i individual'naya organizaciya lechebnogo processa). Moskva: Miklosh; 2010. 320 s.
12. Danilov D.S., Tyul'pin Yu.G. Lechenie shizofrenii. Moskva: Medicinskoe informacionnoe agentstvo; 2010. 276 s.
13. Danilov D.S., Morozova V.D., Luk'yanova T.V. Terapevticheskaya rezistentnost' i metody ee preodoleniya. V kn.: Ivanec NN, redaktor. Sbornik tezisov Vserossiyskoy yubileynoy nauchno-prakticheskoy konferencii s mezhdunarodnym uchastiem «Aktual'nye problemy psihiatrii». Moskva: Pervyy MGMU imeni I.M. Sechenova; 2012. C. 162-164.
14. Pomytkin A.N. Kliniko-biologicheskie aspekty terapevticheskogo otveta na ritmicheskuyu transkranial'nuyu magnitnuyu stimulyaciyu pri rezistentnoy shizofrenii. Dissertaciya kandidata medicinskih nauk. Moskva; 2023. 250 s.
15. Galling B., Roldán A., Hagi K., et al. Antipsychotic augmentation vs monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis. World Psychiatry. 2017 Feb;16(1):77-89. doi:https://doi.org/10.1002/wps.20387
16. Kane J.M., Correll C.U. The role of clozapine in treatment-resistant schizophrenia. JAMAPsychiatry. 2016 Mar;73(3):187-8. doi:https://doi.org/10.1001/jamapsychiatry.2015.2966
17. Kaydan M.A. Shizofreniya, rezistentnaya k antipsihoticheskoy terapii (psihopatologicheskie osobennosti, vozmozhnosti preodoleniya rezistentnosti). Dissertaciya kandidata medicinskih nauk. Moskva; 2025. 153 s.
18. Pomytkin A.N., Tihonov D.V., Kaleda V.G. Augmentaciya terapii rezistentnoy shizofrenii metodom ritmicheskoy transkranial'noy magnitnoy stimulyacii. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2023;123(8):107-114.
19. Stanovaya V.V., Guseynova Z.T., Ivanov M.V., Bigday E.V. Fenomen terapevticheskoy rezistentnosti pri lechenii shizofrenii: vozmozhnosti sovremennoy diagnostiki i metodov protivorezistentnyh vozdeystviy. Obozrenie psihiatrii i medicinskoy psihologii im. V.M. Behtereva. 2023;57(4):120-130.
20. Anand R., Turolla A., Chinellato G., et al. Effect of evenamide, a glutamate inhibitor, in patients with treatment-resistant schizophrenia (TRS): final, 1-year results from a phase 2, open-label, rater-blinded, randomized, international clinical trial. Int J Neuropsychopharmacol.2024 Dec;28(1):pyae061. doi:https://doi.org/10.1093/ijnp/pyae061
21. Cipolla S., Delli Carpini F., Catapano P., et al. Two long-acting antipsychotics in a patient with treatment-resistant schizophrenia: A case report. Clin Pract.2025 Mar;15(3):55. doi:https://doi.org/10.3390/clinpract15030055
22. Moriarty S.E., Parhami P., Parikh J., Galicki L. Antipsychotic polypharmacy for treatment resistant schizoaffective disorder: A case report. Cureus.2025 Mar;17(3):e80204. doi:https://doi.org/10.7759/cureus.80204
23. Ochi S., Kodaka F., Hasegawa N., et al. Associations between clozapine availability, the diagnosis of treatment-resistant schizophrenia subgroups, antipsychotic monotherapy, and concomitant psychotropics among patients with schizophrenia: a real-world nationwide study. Int J Neuropsychopharmacol. 2025 Apr;28(4):pyaf011. doi:https://doi.org/10.1093/ijnp/pyaf011
24. Danilov D.S. Vozmozhnost' formirovaniya remissii vysokogo kachestva pri dlitel'nom hronicheskom techenii shizofrenii. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2008;108(11):80-85.
25. Danilov D.S. Effektivnost' terapii shizofrenii atipichnymi neyroleptikami (znachenie razlichnyh kliniko-social'nyh faktorov). Dissertaciya doktora medicinskih nauk. Moskva; 2011. 439 s.
26. Danilov D.S. Primenenie klozapina pri lechenii shizofrenii. Moskva, Novokuzneck: OAO «Organika»; 2010. 48s.
27. Danilov D.S. Atipichnyy neyroleptik klozapin (azaleptin): spektr terapevticheskih effektov i povtornaya ocenka effektivnosti pri lechenii shizofrenii. Social'nayaiklinicheskayapsihiatriya. 2011;21(4):58-63.
28. Danilov D.S. Klozapin (azaleptin): terapevticheskie vozmozhnosti pri lechenii shizofrenii. Sovremennaya terapiya psihicheskih rasstroystv. 2012;(2):18-24.
29. Chang J.S., Ahn Y.M., Park H.J., et al. Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2008 May;69(5):720-31. doi:https://doi.org/10.4088/jcp.v69n0505
30. Cipriani A., Accordini S., Nosè M., et al. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia: a 12-month, randomized, naturalistic trial. J Clin Psychopharmacol. 2013 Aug;33(4):533-7. doi:https://doi.org/10.1097/JCP.0b013e318296884f
31. Dold M., Leucht S. Pharmacotherapy of treatment-resistant schizophrenia: a clinical perspective. Evid Based Ment Health. 2014 May;17(2):33-7. doi:https://doi.org/10.1136/eb-2014-101813
32. Siskind D.J., Lee M., Ravindran A., et al. Augmentation strategies for clozapine refractory schizophrenia: a systematic review and meta-analysis. Aust N Z J Psychiatry. 2018 Aug;52(8):751-67. doihttps://doi.org/10.1177/0004867418772351
33. Wagner E., Kane J.M., Correll C.U., et al. Clozapine combination and augmentation strategies in patients with schizophrenia – recommendations from an international expert survey among the treatment response and resistance in psychosis (TRRIP) working group. Schizophr Bull.2020 Dec;46(6):1459-70. doi:https://doi.org/10.1093/schbul/sbaa060
34. Correll C.U., Rubio J.M., Inczedy-Farkas G., et al. Efficacy of 42 pharmacologic cotreatment strategies added to antipsychotic monotherapy in schizophrenia: systematic overview and quality appraisal of the meta-analytic evidence. JAMA Psychiatry.2017 Jul;74(7):675-84. doihttps://doi.org/10.1001/jamapsychiatry.2017.0624
35. Kane J.M., Agid O., Baldwin M.L., et al. Clinical guidance on the identification and management of treatment-resistant schizophrenia. J Clin Psychiatry. 2019 Mar;80(2):18com12123. doihttps://doi.org/10.4088/JCP.18com12123
36. Barbui C., Accordini S., Nosè M., et al. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial. J Clin Psychopharmacol. 2011 Jun;31(3):266-73. doi:https://doi.org/10.1097/JCP.0b013e318219cba3
37. Nosè M., Accordini S., Artioli P., et al. Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia. Trials. 2009 May;10:31. doi:https://doi.org/10.1186/1745-6215-10-31
38. Instrukciya po medicinskomu primeneniyu lekarstvennogo preparata Fenazepam®, tabletki, dispergiruemye v polosti rta, RU LP-№(005387)-(RG-RU) ot 07.05.2024.
39. Seredin S.B., Voronina T.A., Neznamov G.G., Zherdev V.P.// Fenazepam: 25 let v medicinskoy praktike, Moskva: «Nauka». – 2007.
