Analysis of the Effectiveness of Psychopharmacotherapy in Patients with Paranoid Schizophrenia with Non-Suicidal Autoaggression and Deficit Personality Changes

Aim. A comparative analysis of the effectiveness of neuroleptics in patients with paranoid schizophrenia with deficit changes at the personal level and non-suicidal auto-aggressive actions (NAA) who are on compulsory treatment.

Design. Full-scale non-randomized longitudinal study

Materials and methods. The study included 237 patients with paranoid schizophrenia during maintenance therapy: 76 people were on risperidone monotherapy, 61 patients received quetiapine, and 100 patients took haloperidol. The clinical effectiveness of therapy was determined by comparative analysis of the frequency of exacerbation of psychotic symptoms, the severity of negative disorders, the frequency of acts of non-suicidal auto-aggression and the level of social functioning. In addition to clinical observation, the Scale of Negative Psychopathology (SANS) and the Social Functioning Scale (PSP) were used. Fisher's test and ANOVA analysis of variance were used to statistically evaluate the data.

Results. All drugs helped reduce the incidence of exacerbation of psychotic disorders, while only with the use of risperidone and haloperidol positive changes in antipsychotic activity were statistically significant (p < 0.01). All drugs helped reduce the severity of negative disorders. When taking risperidone, a statistically significant decrease in disorders associated with flattening and rigidity of affect and attention was noted (p ≤ 0.05). Haloperidol caused a decrease in flattening and rigidity of affect, attention and speech disorders, and apato-abulic syndrome (p ≤ 0.05). All drugs statistically significantly reduced the risk of NAA (p ≤ 0.05), and also contributed to an increase in the level of social functioning of patients, and in patients taking haloperidol, statistically significant changes in this indicator appeared earlier. By the end of the study, while taking each of the drugs included in the study, statistically significant positive changes in the studied parameters were noted (p ≤ 0.05).

Conclusion. The first-line drug for patients with paranoid schizophrenia with deficient personality changes and NAA who are on compulsory treatment is haloperidol. An alternative treatment method for this group of patients may be the administration of risperidone.

1. Dubrovina N.I., Loskutova L.V. Peculiarities of the effect of haloperidol on the development of amnesia in aggressive and submissive mice. Experimental and Clinical Pharmacology. 2002;65(6):3–5. (in Russian)

2. Muranova L.N. The effect of haloperidol on behavioral responses and electrical characteristics of command neurons in the grape snail: abstract of cand. biol. theses. Kazan: Kazan Scientific Center of the Russian Academy of Sciences; 2006. 19 p. (in Russian)

3. Cox J., Witten I.B. Striatal circuits for reward learning and decisionmaking. Nat. Rev. Neurosci. 2019;20(8):482–94. DOI: 10.1038/s41583-019-0189-2

4. Ranjbar-Slamloo Y., Fazlali Z. Dopamine and noradrenaline in the brain; overlapping or dissociate functions? Front. Mol. Neurosci. 2020;12:334. DOI: 10.3389/fnmol.2019.00334

5. Gebreegziabhere Y., Habatmu K., Mihretu A., Cella M. et al. Cognitive impairment in people with schizophrenia: an umbrella review. Eur. Arch. Psychiatry Clin. Neurosci. 2022;272(7):1139–55. DOI: 10.1007/s00406-022-01416-6

6. Howes O.D., Bukala B.R., Beck K. Schizophrenia: from neurochemistry to circuits, symptoms and treatments. Nat. Rev. Neurol. 2024:20(1):22–35. DOI: 10.1038/s41582-023-00904-0

7. Lejeune J.A., Northrop A., Kurtz M.M. A meta-analysis of cognitive remediation for schizophrenia: efficacy and the role of participant and treatment factors. Schizophr. Bull. 2021;47(4):997–1006. DOI: 10.1093/schbul/sbab022

8. McCutcheon R.A., Keefe R.S.E., McGuire P.K. Cognitive impairment in schizophrenia: aetiology, pathophysiology, and treatment. Mol. Psychiatry. 2023;28(5):1902–18. DOI: 10.1038/s41380-023-01949-9

9. Moura B.M., van Rooijen G., Schirmbeck F., Wigman H. et al. A network of psychopathological, cognitive, and motor symptoms in schizophrenia spectrum disorders. Schizophr. Bull. 2021;47(4): 915–26. DOI: 10.1093/schbul/sbab002

10. Arsenault-Mehta K., Hochman-Bérard M., Johnson A., Semenova D. et al. Pharmacological management of neurocognitive impairment in schizophrenia: a narrative review. Neuropsychopharmacol. Rep. 2024;44(1):2–16. DOI: 10.1002/npr2.12382

11. Kristensen T.D., Ambrosen K.S., Raghava J.M., Syeda W.T. et al. Structural and functional connectivity in relation to executive functions in antipsychotic-naïve patients with first episode schizophrenia. Schizophrenia (Heidelb.). 2024;10(1):72. DOI: 10.1038/s41537-024-00487-9

12. Sapienza J., Agostoni G., Comai S., Nasini S. et al. Neuroinflammation and kynurenines in schizophrenia: impact on cognition depending on cognitive functioning and modulatory properties in relation to cognitive remediation and aerobic exercise. Schizophr. Res. Cogn. 2024;38:100328. DOI: 10.1016/j.scog.2024.100328

13. Khosroshahi P.A., Ghanbari M. MicroRNA dysregulation in glutamate and dopamine pathways of schizophrenia: from molecular pathways to diagnostic and therapeutic approaches. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2024;135:111081. DOI: 10.1016/j.pnpbp.2024.111081

14. Slifstein M., Qu W., Gil R., Weinstein J.J. et al. Kappa opioid receptor availability predicts severity of anhedonia in schizophrenia. Neuropsychopharmacology. 2024;49(13):2087–93. DOI: 10.1038/s41386-024-01975-3

15. Kravchenko I.V., Chizhikov I.I., Lvov N.B., Sidorov V.G. et al. Comparative analysis of the effectiveness of neuroleptics in patients with paranoid schizophrenia with tonic type of defect and non-suicidal autoaggressive actions under compulsory treatment. Social and Clinical Psychiatry. 2022;32(2):53–8. (in Russian)

16. Neznanov N.G., Ivanov M.V. Negative and cognitive disorders in endogenous psychoses: diagnostics, clinical features, therapy. M.: MEDpressinform; 2021. 320 p. (in Russian)

17. Shmukler A.B. Schizophrenia. М.: GЕOTAR-Media; 2021. 176 p. (in Russian)

18. Hui C.L.M., Wong A.K.H., Ho E.C.N., Lam B.S.T. et.al. Effectiveness and optimal duration of early intervention treatment in adultonset psychosis: a randomized clinical trial. Psychol. Med. 2023;53(6):2339–51. DOI: 10.1017/S0033291721004189

19. Lyons M., Gupta V., Blaney P.S., Ogenyi A. et al. The complex lived experience of schizophrenia diagnosis: a thematic analysis of online forum posts. Curr. Psychol. 2024;43(30):24878–89. DOI: 10.1007/s12144-024-06175-2

20. Xu Q., Li H., Zhu D. Socioeconomic status, personality, and major mental disorders: a bidirectional Mendelian randomization study. Schizophrenia (Heidelb.). 2024;10(1):49. DOI: 10.1038/s41537-024-00471-3

21. Zenevich G.V. Remissions in schizophrenia. Leningrad: Medicine; 1964. 216 p. (in Russian)

22. Мелехов Д.Е. Клиническая основа оценки работоспособности при шизофрении М.: Медгиз; 1963. 193 с. Melekhov D.E. Clinical basis for assessing performance in schizophrenia M.: Medgiz; 1963. 193 p. (in Russian)

23. Lorentzen E., Mors O., Kjaer J.N. The prevalence of self-harm behavior in schizophrenia spectrum disorders: a systematic review and meta-analysis. Eur. Psychiatry. 2022;65(Suppl.1):S766. DOI: 10.1192/j.eurpsy.2022.1978

24. Chai Y., Tang J.Y., Ma D.C.F., Luo H. et al. Self-harm and suicide rates before and after an early intervention program for patients with firstepisode schizophrenia. JAMA Netw. Open. 2024;7(8):e2426795. DOI: 10.1001/jamanetworkopen.2024.26795

25. Voronkov B.V. Child and adolescent psychiatry. Psychopathology. Diagnostics. Clinic. St. Petersburg: Science and Technology; 2022. 448 p. (in Russian)

26. Vrono M.Sh. Schizophrenia in childhood and puberty. In: Snezhnevsky A.V., ed. Handbook of psychiatry. Vol. 1. M.: Medicine; 1983: 355–72. (in Russian)

27. Panteleeva G.P., Cuculkovskaya M.Ya., Belyaev B.S. Heboid schizophrenia. M.: Medicine; 1986. 192 p. (in Russian)

28. Wang S., Dan Y.L., Yang Y., Tian Y. The shared genetic etiology of antisocial behavior and psychiatric disorders: insights from pleiotropy and causality analysis. J. Affect. Disord. 2024;365: 534–41. DOI: 10.1016/j.jad.2024.08.149

29. Nadzharov R.A. The main stages of the study of schizophrenia and its clinical varieties. In: Snezhnevsky A.V., ed. Schizophrenia. Clinic and pathogenesis. M.: Medicine; 1969: 29–120. (in Russian)

30. Snezhnevsky A.V. Symptomatology and nosology. In: Snezhnevsky A.V., ed. Schizophrenia. Clinic and pathogenesis. M.: Medicine; 1969: 5–28. (in Russian)