Tipik ve Atipik Antipsikotik İlaç Kullanımına Bağlı EEG Anormallikleri

Year 2016, Volume: 21 Issue: 2, 97 - 104, 30.04.2016

Süreyya Ekem Nida Taşçılar Esra Acıman Demirel Banu Özen Barut Handan Ankaralı H. Atasoy

https://doi.org/10.21673/anadoluklin.180733

Abstract

Amaç: Tipik antipsikotikler ve klozapin EEG anormalliklerine ve epileptik nöbetlere neden olabilir.
Yeni kuşak antipsikotiklerin EEG üzerindeki etkileri çok fazla bilinmemektedir. Yapılan bu çalış-
mada klozapin, ketiapin, risperidon ve olanzapin gibi atipik antipsikotikler, amisülpirid, aripiprazol,
paliperidon gibi yeni diğer atipik antipsikotikler ve klorpromazin, haloperidol, zuklopentiksol,
pimozid gibi tipik antipsikotiklerin EEG anormallikleri üzerine etkileri araştırılmıştır.

Gereç ve Yöntemler: Şizofreni veya şizoaffektif bozukluk tanılı 102 hasta prospektif olarak de-
ğerlendirilerek EEG’leri çekildi. Bunların 82’si atipik [klozapin (n:16), risperidon (n:20), ketiapin
(n:10), olanzapin (n:14), diğer yeni atipik antipsikotikler (n:10)] ve tipik [haloperidol (n:5), klorpromazin
(n:2), zuklopentiksol (n:3), pimozid (n:2)] antipsikotik kullanıyordu, 20’si ise ilaç kullanmıyordu.
Bu üç alt grup; cinsiyet ve yaş uyumlu sağlıklı kontrol grubunun (n=29) EEG’leri ile
karşılaştırıldı.

Bulgular: Gruplar arasında demografik özellikler bakımından istatiksel olarak anlamlı fark saptanmadı.
Hem ilaç kullanmayan hastaların hem de sağlıklı kontrollerin EEG’leri normaldi. Klozapin
kullanan hastaların % 31,3’ünde (p < 0,05), ketiapin kullananların da %10’unda (p > 0,05) epileptik
aktivite gözlendi. Epileptik aktivite dışındaki EEG anormallikleri tipik antipsikotik kullananların
%58,3’ünde (p < 0,01), risperidon kullananlarında %35’inde (p < 0,01) saptandı. EEG ketiapin ve yeni
atipik antipsikotik kullananların %80’inde normalken, tipik antipsikotik kullananların %33,3’ünde
normaldi (p=0,012).

Tartışma ve Sonuç: Burada klozapinin en epileptojen antipsikotik olduğunu ve tipik antipsikotiklerin
EEG’yi en fazla bozduğunu bulduk. Ancak klozapin tedavisi alan psikotik hastalarda EEG
bir gerekliliktir. Epilepsinin eklendiği psikotik hastalara yeni atipik antipsikotikler verilebilir, çünkü
EEG üzerine en az istenmeyen etkiler bu ilaçlarla gözlenmiştir. Buna ilaveten antipsikotik ilaçlar
ve epilepsi eşiği arasındaki kompleks ilişkileri açığa çıkarmak için daha fazla bilimsel araştırmaya
ihtiyaç olduğunu da vurgulanmamız lazımdır.

Keywords

elektroensefalografi, tipik antipsikotikler, atipik antipsikotikler, epileptik aktivite

EEG Abnormalities Associated with the Use of Typical and Atypical Antipsychotics,

Abstract

Aim: Typical antipsychotics and clozapine could cause EEG abnormalities and risk of epileptic seizures. Little is known about the effects of newer antipsychotics on EEG. The present study therefore examined the risk of EEG abnormalities associated with the use of atypical antipsychotics [clozapine, quetiapine, risperidone, olanzapine and new atypical antipsychotics (amisulpride, aripiprazole, paliperidone)] and of the typical antipsychotics (chlorpromazine, haloperidol, zuclopenthixol, pimozide).

Materials and Methods: EEG patterns were prospectively investigated in 102 patients with schizophrenia or schizoaffective disorders. While 82 out of the 102 patients were under atypical [clozapine (n=16), risperidone (n=20), quetiapine (n=10), olanzapine (n=14), and new atypical antipsychotics (n=10)] and typical [haloperidol (n=5), chlorpromazine (n=2), zuclopenthixol (n=3), pimozide (n=2)] antipsychotic treatment, 20 of them were not under any treatment. These three groups were compared with a sex- and aged- matched control group of healthy volunteers(n=29).

Results: No statistically significant difference regarding demographic characteristics was found between the groups. Both the patients who were not on any medication and the healthy volunteers had normal EEG’s. Epileptic activity was observed in 31.3% of the patients under clozapine treatment (p<0.05) and in 10% of the patients under quetiapine treatment (p>0.05). EEG abnormalities other than epileptic activity were observed in 58.3% of the patients under typical antipsychotics (p<0.01) and 35% of the patients under risperidone treatment (p<0.01). EEG was normal in 78–80% of the patients using quetiapine and new atypical antipsychotics, compared to 33.3% of the patients under typical antipsychotic treatment (p=0.012). 

Discussion and Conclusion: Herein, we found that clozapine was the most epileptogenic antipsychotic and that typical antipsychoticswere making the worse EEG changes. Nevertheless, in the psychotic patients under clozapine treatment EEG is a must. Psychotic patients with consequential epilepsy could be given new atypical antipsychotics because it has the least unwanted effects on EEG. Moreover, it should also be emphasized that there is a need for further scientific research to clarify all aspects characterizing the complex link between seizure threshold and psychotropic drugs.

Keywords

electroencephalography, typical antipsychotics, atypical antipsychotics, epileptic activity

References

• Centorrino F, Price BH, Tuttle M, Bahk WM, Hennen J, Albert MJ, et al. EEG abnormalities during treatment with typical and atypical antipsychotics. Am J Psychiatry. 2002;159(1):109–15.
• Roubicek J, Major I. EEG profile and behavioral changes after a single dose of clozapine in normals and schizophrenics. Biol Psychiatry. 1977;12(5):613–33.
• Moore NC, Tucker KA, Brin FB, Merai P, Shillcut SD, Coburn KL. Positive symptoms of schizophrenia: Response to haloperidol and remoxipride is associated with increased alpha EEG activity. Hum Psychopharmacol. 1999;12(1):75–80.
• Stevens JR, Bigelow L, Denney D, Lipkin J, Livermore AH, Rauscher F, et al. Telemetered EEG-EOG during psychotic behaviors of schizophrenia. Arch Gen Psychiatry. 1979;36(3):251–62.
• Bridgers SL. Epileptiform abnormalities discovered on electroencephalographic screening of psychiatric inpatients. Arch Neurol. 1987;44(3):312–6.
• Silvestri RC, Bromfield EB, Khoshbin S. Clozapine-induced seizures and EEG abnormalities in ambulatory psychiatric patients. Ann Pharmacother. 1998;32(11):1147–51.
• Devinsky O, Honigfeld G, Patin J. Clozapine-related seizures. Neurology 1991;41(3):369–71.
• Baldessarini RJ. Drugs and the treatment of psychiatric disorders: depression and anxiety disorders. In: Hardman JG, Limbird LE, Gilman AG (ed.), Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10. ed. New York: McGraw-Hill; 2001:447–83.
• Amerikan Psikiyatri Birliği. Psikiyatride Hastalıkların Tanımlanması ve Sınıflandırılması El Kitabı, 4. ed. (DSM-IV TR), (çev. Ertuğrul Köroğlu). Ankara: Hekimler Yayın Birliği; 2001:137–42.
• American Electroencephalographic Society. Guideline seven: a proposal for standard montages to be used in clinical EEG. J Clin neurophsiol. 1994;11(1):30–6.
• Small JG. Psychiatric disorders and EEG. In: Niedermeyer E, DaSilva FL (ed.), Electroencephalography: Basic Principles, Clinical Applications, and Related Fields, 5. ed. Baltimore: Lippincott Williams & Wilkins; 1999:639–61.
• Aminoff MJ. Electroencephalography: general principles and clinical applications. In: Aminoff MJ (ed.), Electrodiagnosis in Clinical Neurology, 3. ed. New York: Churchill-Livingstone; 1992:41–91.
• Saletu B, Anderer P, Kinsperger K, Grünberger J. Topographic brain mapping of EEG in neuropsychopharmacology. Part II: Clinical applications (pharmaco EEG imaging). Methods Find Exp Clin Pharmacol.1987;9(6):385–408.
• Westphal KP, Grozinger B, Diekmann V, Scherb W, Reess J, Leibing U, et al. Slower theta activity over the midfrontal cortex in schizophrenic patients. Acta Psychiatr Scand. 1990;81(2):132–8.
• Jirsch JD, Urrestarazu E, LeVan P, Olivier A, Dubeau F, Gotman J. High-frequency oscillations during human focal seizures. Brain. 2006;129(6):1593–608.
• Staba RJ, Wilson CL, Bragin A, Fried I, Engel J Jr. Quantitative analysis of high-frequency oscillations (80-500 Hz) recorded in human epileptic hippocampus and entorhinal cortex. J Neurophysiol. 2002;88(4):1743–52.
• Yağcıoğlu EA. Antipsikotik ilaçların etki mekanizmaları: şizofreni tedavisinde “atipiklik” bir üstünlük mü? Türk Psikiyatri Derg. 2007;18(4):364–74.
• Amann BL, Pogarell O, Mergl R, Juckel G, Grunze H, Mulert C, et al. EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects. Hum Psychopharmacol. 2003;18(8):641–6.
• Miller AL, Hall CS, Buchanan RW, Buckley PF, Chiles JA, Conley RR, et al. The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2003 update. J Clin Psychiatry. 2004;65(4):500–8.
• Farah A. Atypicality of atypical antipsychotics. Prim Care Companion J Clin Psychiatry. 2005;7(6):268–74.
• Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry. 1991;148(11):1474–86.
• Herz MI, Marder SR. Schizophrenia: Comprehensive Treatment and Management. Philadelphia: Lippincott Williams & Wilkins; 2002:9–21.
• Conley RR, Meltzer HY. Adverse events related to olanzapine. J Clin Psychiatry. 2000;61(Suppl 8):26–9.
• Kramer M, Simpson G, Maciulis V, Kushner S, Vijapurkar U, Lim P, et al. Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebocontrolled study. J Clin Psychopharmacol. 2007;27(1):6–14.
• Olney JW, Farber NB Efficacy of clozapine compared with other antipsychotics in preventing NMDA-antagonist neurotoxicity. J Clin Psychiatry. 1994;55(Suppl B):43–6.
• Welch J, Manschreck T, Redmond D. Clozapine-induced seizures and EEG changes. J Neuropsychiatry Clin Neurosci. 1994;6(3):250–6.
• Ichikawa J, Dai J, O’Laughlin IA. Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum. Neuropsychopharmacology 2002;26(3):325–39.
• Risby ED, Epstein CM, Jewart RD, Nguyen BV, Morgan WN, Risch SC, et al. Clozapine-induced EEG abnormalities and clinical response to clozapine. J Neuropsychiatry Clin Neurosci. 1995;7(4):466–70.
• Freudenreich O, Weiner RD, McEvoy JP. Clozapine-induced electroencephalogram changes as a function of clozapine serum levels. Biol Psychiatry. 1997;42(2):132–37.
• Baldessarini RJ, Frankenburg FR. Clozapine: a novel antipsychotic agent. N Engl J Med. 1991;324(11):746–54.
• Wetzel H, Szegedi A, Hain C, Wiesner J, Schlegel S, Benkert O. Seroquel (ICI 204 636), a putative “atypical” antipsychotic, in schizophrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinological and EEG parameters. Psychopharmacology (Berl) 1995;119(2):231–8.
• Chengappa KN, Pollock BG, Parepally H, Levine J, Kirshner MA, Brar JS, et al. Anticholinergic differences among patients receiving standard clinical doses of olanzapine or clozapine. J Clin Psychopharmacol. 2000;20(3):311–6.
• Beasley CM Jr, Tollefson GD, Tran PV. Safety of olanzapine. J Clin Psychiatry. 1997;58(Suppl 10):13–7.
• Wyderski RJ, Starrett WG, Abou-Saif A. Fatal status epilepticus associated with olanzapine therapy. Ann Pharmacother. 1999;33(7–8):787–9.
• Stahll SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Application, 3. ed. New York: Cambridge University Press; 2008:401–50.
• Jufe G. Psicofarmacología Práctica. Buenos Aires: Editorial Polemos; 2001:129–40.
• Bezchlibnyk-Butler KZ, Jeffries JJ. Clinical handbook of psychotropic drugs,13. ed. Toronto: Hogrefe & Huber Publishers; 2003:100–29.
• Strange PG. Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol Rev. 2001;53(1):119–33.