Clozapine in epilepsy and psychosis: effects on seizures and metabolic profile
Main Article Content
Keywords
Epilepsy, Psychotic Disorders, Clozapine, Weight Gain, Hyperlipidemias
Abstract
Background: Clozapine (CZP) is an antipsychotic used in resistant psychosis, but has adverse metabolic effects and is associated with new onset or worsening of epileptic seizures (ES). There is not enough information available regarding its effect on metabolic variables and on ES in patients with epilepsy.
Objective: To describe the effect of CZP on the metabolic and hematologic profiles, and on ES in patients with epilepsy and with psychosis and/or aggressive behavior.
Methods: A case series of patients with epilepsy and psychosis and/or aggressive behavior that received CZP with an 18-week follow-up. Clinical records were assessed from 2008-2018. 30 patients with epilepsy that received CZP were included. A paired analysis (Student’s t-test or Wilcoxon signed rank test) was performed with metabolic variables (glucose, cholesterol, and triglycerides), hematologic variables, weight, body mass index (BMI), and monthly ES before and after CZP administration.
Results: The median age to CZP initiation was 31.9 ± 16.07 years. Median CZP dosage was 193 mg/day. There were changes on BMI (p = 0.001; 3.2 kg/m2 increase, median = 3.08), triglycerides (p = 0.002) and glucose (p = 0.030). Weight increase was 7 kg (p = 0.292; median = 4 kg). Monthly ES mean was decreased from 4.9 (median = 2) to 2.04 (median = 1; p = 0.001).
Conclusions: This study provide information regarding the security profile of CZP in patients with epilepsy with psychosis and/or aggressive behavior. A decrease on monthly ES was observed, as well as moderate increases in triglycerides, glucose and BMI, which coincide with that described by other authors.
References
1. Crilly J. The history of clozapine and its emergence in the US market:a review and analysis. Hist Psychiatry. 2007;18(1):39-60. doi:10.1177/0957154X07070335
2. Stephens P. A review of clozapine:an antipsychotic for treatment-resistant schizophrenia. Compr Psychiatry. 1990;31(4):315-26. doi:10.1016/0010-440X(90)90038-T
3. Buchanan RW. Clozapine:efficacy and safety. Schizophrenia Bull. 1995;21(4):579-91. doi:10.1093/schbul/21.4.579
4. Williams AM, Park SH. Seizure associated with clozapine:incidence, etiology, and management. CNS Drugs. 2015;29(2):101-11. doi:10.1007/s40263-014-0222-y
5. Wong J, Delva N. Clozapine-induced seizures:recognition and treatment. Can J Psychiatry. 2007;52(7):457-63. doi:10.1177/070674370705200708
6. Liukkonen J, Koponen HJ, Nousiainen U. Clinical picture and long-term course of epileptic seizures that occur during clozapine treatment. Psychiatry Res. 1992;44(2):107-12. doi:10.1016/0165-1781(92)90045-5
7. Kikuchi YS, Sato W, Ataka K, Yagisawa K, Omori Y, Kanbayashi T, et al. Clozapine-induced seizures, electroencephalography abnormalities, and clinical responses in Japanese patients with schizophrenia. Neuropsychiatr Dis Treat. 2014;10:1973-8. doi:10.2147/NDT.S69784
8. Silvestri RC, Bromfield EB, Khoshbin S. Clozapine-induced seizures and EEG abnormalities in ambulatory psychiatric patients. Ann Pharmacother. 1998;32(11):1147-51. doi:10.1345/aph.18062
9. Varma S, Bishara D, Besag FM, 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
10. Devinsky O, Pacia SV. Seizures during clozapine therapy. J Clin Psychiatry. 1994;55 (Suppl B):153-6
11. Ohno-Shosaku T, Sugawara Y, Muranishi C, Nagasawa K, Kubono K, Aoki N, et al. Effects of clozapine and N-desmethylclozapine on synaptic transmission at hippocampal inhibitory and excitatory synapses. Brain Res. 2011;1421:66-77. doi:10.1016/j.brainres.2011.08.073
12. Edge SC, Markowitz JS, Devane CL. Clozapine drug-drug interactions:a review of the literature. Human Psychopharmacol. 1997;12:5-20. doi:10.1002/(SICI)1099-1077(199701/02)12:1
13. Caetano D. Use of anticonvulsants as prophylaxis for seizures in patients on clozapine. Australas Psychiatry. 2014;22(1):78-82. doi:10.1177/1039856213502829
14. Kanner AM, Rivas-Grajales AM. Psychosis of epilepsy:a multifaceted neuropsychiatric disorder. CNS Spectr. 2016;21(3):247-57. doi:10.1017/S1092852916000250
15. Toone BK. The psychoses of epilepsy. J Neurol Neurosurg Psychiatry. 2000;69(1):1-3. doi:10.1136/jnnp.69.1.1
16. Sachdev P. Schizophrenia-like psychosis and epilepsy:the status of the association. Am J Psychiatry. 1998;155(3):325-36. doi:10.1176/ajp.155.3.325
17. de Araujo Filho GM, da Silva JM, Mazetto L, Marchetti RL, Yacubian EM. Psychoses of epilepsy:a study comparing the clinical features of patients with focal versus generalized epilepsies. Epilepsy Behav. 2011;20(4):655-8. doi:10.1007/978-3-319-22159-5_19
18. Swinkels WA, Kuyk J, van Dyck R, Spinhoven P. Psychiatric comorbidity in epilepsy. Epilepsy Behav. 2005;7(1):37-50. doi:10.1016/j.yebeh.2005.04.012
19. Rayport M, Ferguson SM. Psychosis of epilepsy:an integrated approach. En:Ettinger AB, Kanner AM, editores. Psychiatric aspects of epilepsy:a practical guide to diagnosis and treatment. Baltimore:Lippincott, Williams and Wilkins;1998. 73-94. doi:10.1017/S1092852916000250
20. Sachdev PS. Alternating and postictal psychoses:review and a unifying hypothesis. Schizophr Bull. 2007;33(4):1029-37. doi:10.1093/schbul/sbm012
21. Farooq S, Sherin A. Interventions for psychotic symptoms concomitant with epilepsy. Cochrane Database Syst Rev. 2015;(12):CD006118. doi:10.1002/14651858.CD006118.pub2
22. Blumer D, Wakhlu S, Montouris G, Wyler AR. Treatment of the interictal psychoses. J Clin Psychiatry. 2000;61(2):110-22. doi:10.4088/jcp.v61n0206
23. Toone BK, Garralda ME, Ron MA. The psychoses of epilepsy and the functional psychoses:a clinical and phenomenological comparison. Br J Psychiatry. 1982;141:256-61. doi:10.1192/bjp.141.3.256
24. Jette Pomerleau V, Dubeau F, Ducharme S. Clozapine safety and efficacy for interictal psychotic disorder in pharmacoresistant epilepsy. Cogn Behav Neurol. 2017;30(2):73-6. doi:10.1097/WNN.0000000000000127
25. Langosch J, Trimble M. Epilepsy, psychosis and clozapine. Hum Psychopharmacol. 2002;17(2):115-9. doi:10.1002/hup.375
26. Antony JT, Elias A, Chacko F, Rajan B. Is clozapine safe in patients with preexisting epilepsy?A report of 2 cases. J Clin Psychiatry. 2008;69(2):328-9. doi:10.4088/jcp.v69n0221e
27. Agrawal N, Mula M. Treatment of psychoses in patients with epilepsy:an update. Ther Adv Psychopharmacol. 2019;9:2045125319862968. doi:10.1177/2045125319862968
28. Daly M, Salloway M. Clozapine-induced seizures and EEG changes:a case report and discussion of clinical management. Jefferson Journal of Psychiatry. 1993;11(1):8. doi:10.29046/JJP.011.1.011
29. Muñoz P, Gallardo R. Trastornos metabólicos en pacientes esquizofrénicos tratados con clozapina. Revista Chilena de Neuro-psiquiatría. 2004;42(1):37-42. doi:10.4067/S0717-92272004000100005
30. Lamberti JS, Bellnier T, Schwarzkopf SB. Weight gain among schizophrenic patients treated with clozapine. Am J Psychiatry. 1992;149(5):689-90. doi:10.1176/ajp.149.5.689
31. Iqbal MM, Rahman A, Husain Z, Mahmud SZ, Ryan WG, Feldman JM. Clozapine:a clinical review of adverse effects and management. Ann Clin Psychiatry. 2003;15(1):33-48. doi:10.1023/a:102322↲309
32. Lally J, Gallagher A, Bainbridge E, Avalos G, Ahmed M, McDonald C. Increases in triglyceride levels are associated with clinical response to clozapine treatment. J Psychopharmacol. 2013;27(4):401-3. doi:10.1177/0269881112472
33. Boston PF, Dursun SM, Reveley MA. Cholesterol and mental disorder. Br J Psychiatry. 1996;169(6):682-9. doi:10.1192/bjp.169.6.682
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