Comparative analysis of EEG in patients with schizophrenia receiving various atypical antipsychotics

Aim. To conduct a comprehensive analysis of EEG recordings of schizophrenia patients receiving atypical antipsychotics as monotherapy.

Materials and methods. We examined 94 patients with schizophrenia aged 33 [28; 40] years with a disease duration of 10 [4; 15] years. The patients were divided into 5 groups depending on the antipsychotic drugs they took: 1) risperidone – 31 patients; 2) quetiapine – 20 patients; 3) aripiprazole – 11 patients; 4) olanzapine – 13 patients; 5) clozapine – 19 patients. EEG was recorded during wakefulness with closed eyes (background test), 3-minute hyperventilation, and rhythmic photostimulation in all patients. To describe and interpret the received recordings, the EEG classification according to J. Micoulaud – Franchi et al. was used.

Results. EEG modifications (score > 1A) were observed in 61.7% (n = 58) of patients. In the group of patients receiving risperidone, EEG modifications were found in 48.4% of cases, in patients taking quetiapine – in 70% of cases, aripiprazole – in 63.6% of cases, olanzapine – in 61.5% of cases, clozapine – in 73.7% of cases. The frequency of epileptiform patterns in patients receiving olanzapine was significantly higher than in those taking risperidone (p = 0.033) and clozapine (p = 0.032). Slowing in the EEG (score > 1) was more often observed in patients taking clozapine – 63.2% (n = 12), olanzapine – 61.5% (n = 8), and quetiapine – 60% (n = 12). Slower EEG waves were less common in patients receiving aripiprazole – 45.5% (n = 5) and risperidone – 45.2% (n = 14). In the group of patients with EEG slowing (score > 1), the dose of chlorpromazine equivalent was significantly greater compared to patients with normal EEG (p = 0.00046).

Conclusion. The data obtained demonstrate changes in EEG parameters during monotherapy with atypical antipsychotics and indicate their dose-dependent effect on the bioelectrical activity of the brain.

1. Galderisi S., Sannita W.G. Pharmaco-EEG: A history of progress and a missed opportunity. Clin. EEG Neurosci. 2006;37(2):61–65. DOI: 10.1177/155005940603700204.

2. Dasberg H., Robinson S. The influence of anti-psychotic drugs on the EEG of mental patients. Electroencephalogr. Clin. Neurophysiol. 1970; 8(6):643.

3. Dasberg H., Robinson S. Electroencephalographic variations following anti-psychotic drug treatment. (Diagnostic and prognostic significance). Dis. Nerv. Syst. 1971;32(7):472–478.

4. Galkin S.A., Roshchina O.V., Kisel N.I., Ivanova S.A., Bokhan N.A. Clinical and neurophysiological characteristics of alcohol dependence and its comorbidity with affective disorders. Neuroscience and Behavioral Physiology. 2021;51(6):720–723. DOI: 10.1007/s11055–021–01127–w.

5. Изнак Е.В., Дамянович Е.В., Левченко Н.С., Олейчик И.В., Изнак А.Ф. Асимметрии ЭЭГ у пациенток юношеского возраста при депрессиях с разными видами аутоагрессивного поведения. Психиатрия. 2020;18(3):14–21. DOI: 10.30629/2618–6667–2020–18–3–14–21.

6. Арзуманов Ю.Л., Лапин И.А., Мещеряков А.Ф., Бродянский В.М., Абакумова А.А., Винникова М.А. и др. Электрофизиологические корреляты генетического риска развития алкогольной зависимости. Вопросы наркологии. 2016;(2):5–23.

7. Галкин С.А., Пешковская А.Г., Рощина О.В., Кисель Н.И., Иванова С.А., Бохан Н.А. Особенности мозговой активности при алкогольной зависимости в задаче на ингибиторный контроль. Бюллетень сибирской медицины. 2020;19(4):38–45. DOI: 10.20538/1682–0363–2020–4–38–45.

8. Kutepov I.E., Krysko A.V., Dobriyan V.V., Yakovleva T.V., Krylova E.Yu., Krysko V.A. Visualization of eeg signal entropy in schizophrenia. Scientific Visualization. 2020;12(1):1–9. DOI: 10.26583/sv.12.1.01.

9. Boutros N.N. Psychotic and Affective Disorders. In: Standard EEG: A Research Roadmap for Neuropsychiatry. Springer, Cham. 2013. DOI: 10.1007/978–3–319–04444–6_11.

10. O’Sullivan S.S., Mullins G.M., Cassidy E.M., McNamara B. The role of the standard EEG in clinical psychiatry. Hum. Psychopharmacol. 2006;21(4):265–271. DOI: 10.1002/hup.767.

11. Itil T.M. The use of electroencephalography in the practice of psychiatry. Psychosomatics. 1982;23(8):799–803. DOI: 10.1016/S0033–3182(82)73079–8.

12. Aiyer R., Novakovic V., Barkin R.L. A systematic review on the impact of psychotropic drugs on electroencephalogram waveforms in psychiatry. Postgrad. Med. 2016;128(7):656– 664. DOI: 10.1080/00325481.2016.1218261.

13. Dias Alves M., Micoulaud-Franchi J.A., Simon N., Vion-Dury J. Electroencephalogram modifications associated with atypical strict antipsychotic monotherapies. J. Clin. Psychopharmacol. 2018;38(6):555–562. DOI: 10.1097/JCP.0000000000000953.

14. Kikuchi Y.S., Sato W., Ataka K., Yagisawa K., Omori Y., Kanbayashi T., Shimizu T. Clozapine–induced seizures, electroencephalography abnormalities, and clinical responses in Japanese patients with schizophrenia. Neuropsychiatr. Dis. Treat. 2014;10:1973–1978. DOI: 10.2147/NDT.S69784.

15. Centorrino F., Price B.H., Tuttle M., Bahk W.M., Hennen J., Albert M.J. et al. EEG abnormalities during treatment with typical and atypical antipsychotics. Am. J. Psychiatry. 2002;159(1):109–115. DOI: 10.1176/appi.ajp.159.1.109.

16. Pillmann F., Schlote K., Broich K., Marneros A. Electroencephalogram alterations during treatment with olanzapine. Psychopharmacology (Berl.). 2000;150(2):216–219. DOI: 10.1007/s002130000426.

17. Wichniak A., Szafranski T., Wierzbicka A., Waliniowska E., Jernajczyk W. Electroencephalogram slowing, sleepiness and treatment response in patients with schizophrenia during olanzapine treatment. J. Psychopharmacol. 2006;20(1):80–85. DOI: 10.1177/0269881105056657.

18. Amann B.L., Pogarell O., Mergl R., Juckel G., Grunze H., Mulert C., Hegerl U. EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects. Hum. Psychopharmacol. 2003;18(8):641–646. DOI: 10.1002/hup.537.

19. Micoulaud-Franchi J.A., Balzani C., Faugere M. Neurophysiologie clinique en psychiatrie : 1 – Techniques, vocabulaires et indications de l’électroencéphalographie conventionnelle. Annales Médico-psychologiques, Revue Psychiatrique. 2013;171(5):334–341. DOI: 10.1016/j.amp.2013.04.005.

20. Wu C.S., Wang S.C., Yeh I.J., Liu S.K. Comparative risk of seizure with use of first- and second-generation antipsychotics in patients with schizophrenia and mood disorders. J. Clin. Psychiatry. 2016;77(5):e573–579. DOI: 10.4088/JCP.15m09898.

21. Varma S., Bishara D., Besag F.M., Taylor D. Clozapine-related EEG changes and seizures: dose and plasma-level relationships. Ther. Adv. Psychopharmacol. 2011;1(2):47–66. DOI: 10.1177/2045125311405566.

22. Degner D., Nitsche M.A., Bias F., Rüther E., Reulbach U. EEG alterations during treatment with olanzapine. Eur. Arch. Psychiatry Clin. Neurosci. 2011;261(7):483–488. DOI: 10.1007/s00406–011–0208–4.

23. Matsuura M., Yoshino M., Ohta K., Onda H., Nakajima K., Kojima T. Clinical significance of diffuse delta EEG activity in chronic schizophrenia. Clin. Electroencephalogr. 1994;25(3):115–121. DOI: 10.1177/155005949402500309.

24. Марусин А.В., Корнетов А.Н., Сваровская М.Г., Вагайцева К.В., Павленюк Е.С., Степанов В.А. Ассоциация генов подверженности к алкоголизму, шизофрении и болезни Альцгеймера с психодиагностическими признаками в популяции русских. Бюллетень сибирской медицины. 2016;15(5):83–96. DOI: 10.20538/1682–0363–2016–5–83–96.

25. Kornetov A. Old age psychiatry: training in Siberia. Mental Health Reforms. 2002;7(2):7–8.

26. Carli M., Kolachalam S., Longoni B., Pintaudi A., Baldini M., Aringhieri S. et al. Atypical antipsychotics and metabolic syndrome: from molecular mechanisms to clinical differences. Pharmaceuticals (Basel). 2021;14(3):238. DOI: 10.3390/ph14030238.