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Review

Optimizing co-prescription of clozapine and antiseizure medications: a systematic review and expert recommendations for clinical practice

, &
Pages 347-358 | Received 15 Jan 2024, Accepted 10 Apr 2024, Published online: 18 Apr 2024

References

  • Caetano D. Use of anticonvulsants as prophylaxis for seizures in patients on clozapine. Australas Psychiatr. 2014;22(1):78–82. doi: 10.1177/1039856213502829
  • Williams AM, Park SH. Seizure associated with clozapine: incidence, etiology, and management. CNS Drugs. 2015;29(2):101–111. doi: 10.1007/s40263-014-0222-y
  • Spina E, Leon J. Potentially clinically relevant pharmacodynamic interactions between antiepileptic drugs and psychotropic drugs: an update. Curr Pharm Des. 2017;23(37):5625–5638. doi: 10.2174/1381612823666170809102258
  • Panić B, Jovanović M, Lukić V, et al. Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid. Eur J Clin Pharmacol. 2023;79(11):1557–1564. doi: 10.1007/s00228-023-03569-2
  • Tsukahara M, So R, Yoshimura Y, et al. Effect of smoking habits and concomitant valproic acid use on relapse in patients with treatment-resistant schizophrenia receiving clozapine: a 1-year retrospective cohort study. Acta Psychiatr Scand. 2023;148(5):437–446. doi: 10.1111/acps.13612
  • Ratanajamit C, Musakopas C, Vasiknanonte S, et al. Incidence and risk for neutropenia/agranulocytosis among clozapine users: a retrospective cohort study. Int J Psychiatr Clin Pract. 2010;14(2):109–115. doi: 10.3109/13651500903402450
  • Malik S, Lally J, Ajnakina O, et al. Sodium valproate and clozapine induced neutropenia: A case control study using register data. Schizophr Res. 2018;195:267–273. doi: 10.1016/j.schres.2017.08.041
  • Gerson SL, Lieberman JA, Friedenberg WR, et al. Polypharmacy in fatal clozapine-associated agranulocytosis. Lancet. 1991;338(8761):262–263. doi: 10.1016/0140-6736(91)90410-Q
  • Meyer N, Gee S, Whiskey E, et al. Optimizing outcomes in clozapine rechallenge following neutropenia: a cohort analysis. J Clin Psychiatr. 2015;76(11):e1410–e1416. doi: 10.4088/JCP.14m09326
  • Yang CC, Wang XY, Chou PH, et al. Valproate-related neutropenia and lithium-related leukocytosis in patients treated with clozapine: a retrospective cohort study. BMC Psychiatry. 2023;23(1):170. doi: 10.1186/s12888-023-04659-2
  • Taylor D. Pharmacokinetic interactions involving clozapine. Brit J Psychiatr. 1997;171(2):109–112. doi: 10.1192/bjp.171.2.109
  • de Leon J, Santoro V, D’Arrigo C, et al. Interactions between antiepileptics and second-generation antipsychotics. Expert Opinion on Drug Metab Toxicol. 2012;8(3):311–334. doi: 10.1517/17425255.2012.660918
  • Spina E, Pisani F, de Leon J. Clinically significant pharmacokinetic drug interactions of antiepileptic drugs with new antidepressants and new antipsychotics. Pharmacol Res. 2016a;106:72–86. doi: 10.1016/j.phrs.2016.02.014
  • de Leon J. Future studies on the interaction between clozapine and valproic acid should aspire to include longitudinal designs and free valproate concentrations, and should consider that Inducer and/or inhibitory effects may vary with time, the individual, and the auto-induction of valproic acid. Ther Drug Monit. 2020;42(1):159–161. doi: 10.1097/FTD.0000000000000705
  • Chopra N, de Leon J. Clozapine-induced myocarditis may be associated with rapid titration: a case report verified with autopsy. Int J Psychiatr Med. 2016;51(1):104–115. doi: 10.1177/0091217415621269
  • de Leon J, Schoretsanitis G, Smith RL, et al. An international adult guideline for making clozapine titration safer by using six ancestry-based personalized dosing titrations, CRP, and clozapine levels. Pharmacopsychiatry. 2022;55:73–86. doi: 10.1055/a-1625-6388
  • Vickers M, Ramineni V, Malacova E, et al. Risk factors for clozapine‐induced myocarditis and cardiomyopathy: a systematic review and meta‐analysis. Acta Psychiatr Scand. 2022;145(5):442–455. doi: 10.1111/acps.13398
  • Siskind DJ, Lee M, Ravindran A, et al. Augmentation strategies for clozapine refractory schizophrenia: a systematic review and meta-analysis. Aust NZ J Psychiatr. 2018;52(8):751–767. doi: 10.1177/0004867418772351
  • Wagner E, Löhrs L, Siskind D, et al. Clozapine augmentation strategies – a systematic meta-review of available evidence. Treatment options for clozapine resistance. J Psychopharmacol. 2019;33(4):423–435. doi: 10.1177/0269881118822171
  • Wagner E, Kane JM, Correll CU, 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;46:1459–1470. doi: 10.1093/schbul/sbaa060
  • Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71
  • Besag FM, Berry D. Interactions between antiepileptic and antipsychotic drugs. Drug Saf. 2006;29(2):95–118. doi: 10.2165/00002018-200629020-00001
  • Diaz FJ, Eap CB, Ansermot N, et al. Can valproic acid be an inducer of clozapine metabolism? Pharmacopsychiatry. 2014;47(3):89–96. doi: 10.1055/s-0034-1371866
  • Spina E, Hiemke C, de Leon J. Assessing drug-drug interactions through therapeutic drug monitoring when administering oral second-generation antipsychotics. Expert Opin Drug Metab Toxicol. 2016;12(4):407–422. doi: 10.1517/17425255.2016.1154043
  • Yousra H, Pierrick L, Laurent L, et al. Interaction between clozapine and oxcarbazepine: a case report. Ther Adv Psychopharmacol. 2017;7(2):95–99. doi: 10.1177/2045125316681472
  • Smith RL, Kyllesø L, Haslemo T, et al. Reduction in N-Desmethylclozapine level is determined by daily dose but not serum concentration of valproic acid-indications of a presystemic interaction mechanism. Ther Drug Monit. 2019;41:503–508. doi: 10.1097/FTD.0000000000000619
  • Errasoul AH, Alarabi MA. Factors predicting serum clozapine levels in middle eastern patients: an observational study. BMC Psychiatry. 2022;22(1):269. doi: 10.1186/s12888-022-03910-6
  • Sangüesa E, Cirujeda C, Concha J, et al. Pharmacokinetic interactions between clozapine and valproic acid in patients with treatment-resistant schizophrenia: Does UGT polymorphism affect these drug interactions? Chem Biol Interact. 2022;364:110042. doi: 10.1016/j.cbi.2022.110042
  • Santos RT, Mullen S, Crouse EL, et al. Comparison of clozapine doses and tolerability in patients with and without concurrent valproic acid. Ment Health Clin. 2022;12(6):336–341. doi: 10.9740/mhc.2022.12.336
  • Smith RL, Wollmann BM, Kyllesø L, et al. Effect of valproic acid on the metabolic spectrum of clozapine in patients with schizophrenia. J Clin Psychopharmacol. 2022;42(1):43–50. doi: 10.1097/JCP.0000000000001507
  • Schoretsanitis G, Anıl Yağcıoğlu AE, Ruan CJ, et al. Clozapine ultrarapid metabolism during weak induction probably exists but requires careful diagnosis. A literature review, five new cases and a proposed definition. Schizophr Res. 2024. doi: 10.1016/j.schres.2023.05.010. in press.
  • Pantelis C, Adesanya A. Increased risk of neutropaenia and agranulocytosis with sodium valproate used adjunctively with clozapine. Aust NZ J Psychiatr. 2001;35:544–545.
  • Madeb R, Hirschmann S, Kurs R, et al. Combined clozapine and valproic acid treatment-induced agranulocytosis. Eur Psychiatr. 2002;17:238–239. doi: 10.1016/S0924-9338(02)00659-4
  • Behar D, Schaller JL. Topiramate leukopenia on clozapine. Europ Child Adol Psychiatr. 2004;13(1):51–52. doi: 10.1007/s00787-004-0323-0
  • Imbarlina MJ, Sarkar S, Marwah S, et al. Leukopenia in clozapine treated patients may be induced by other drugs: a case series. Eur Psychiatry. 2004;19(8):506–509. doi: 10.1016/j.eurpsy.2004.09.007
  • Tang C, Lee J, Hariram J. Thrombocytopenia with valproate and clozapine combination therapy. Asean J Psychiatr. 2011;12:122–125.
  • Tourian L, Margolese HC. Late-onset agranulocytosis in a patient treated with clozapine and lamotrigine. J Clin Psychopharmacol. 2011;31(5):665–667. doi: 10.1097/JCP.0b013e31822c29db
  • Tellez J, Dragonetti J, Ahmed I. Use of valproate and clozapine during course of chemoradiation in a patient with malignancy. Psycho-Oncol. 2019;28(8):1767–1769. doi: 10.1002/pon.5152
  • Jakobsen MI, Grønborg H, Hansen HV, et al. Clozapine-associated neutropenia following augmentation with sodium valproate. SAGE Open Med Case Rep. 2021;9:2050313x211019791. doi: 10.1177/2050313X211019791
  • Cerulli TR. Clozapine-associated pancreatitis. Harv Rev Psychiatr. 1999;7(1):61–63. doi: 10.3109/hrp.7.1.61
  • Bhatti MA, Zander J, Reeve E. Clozapine-induced pericarditis, pericardial tamponade, polyserositis, and rash. J Clin Psychiatr. 2005;66:1490–1491. doi: 10.4088/JCP.v66n1121a
  • Waller H, Porter R, Ritz S, et al. Late occurrence of clozapine-associated polyserositis. Int J Neuropsychopharmacol. 2007;10(1):147–148. doi: 10.1017/S1461145706006961
  • Fernández-Pérez R, Alvarez-Dobaño JM, Suárez-Antelo J, et al. Eosinophilic pleural effusion associated with the addition of sodium valproate. J Clin Psychopharmacol. 2009;29(3):310–311. doi: 10.1097/JCP.0b013e3181a2e1cf
  • Bowen DJ, Lucas NL, Braude S. Persistent febrile illness with multisystem organ failure associated with clozapine. Int Med J. 2012;42(1):104–106. doi: 10.1111/j.1445-5994.2011.02607.x
  • Mohan T, Chua J, Kartika J, et al. Clozapine-induced nephritis and monitoring implications. Aust N Z J Psychiatry. 2013;47:586–587. doi: 10.1177/0004867412470170
  • De Berardis D, Campanella D, Serroni N, et al. Clozapine-related pericarditis during titration phase in a patient with resistant schizophrenia and concomitant valproate treatment: a case report. J Clin Psychopharmacol. 2014;34(5):649–651. doi: 10.1097/JCP.0000000000000179
  • Chopra N, de Leon J. Clozapine-induced myocarditis may be associated with rapid titration: a case report verified with autopsy. Int J Psychiatry Med. 2016;51(1):104–115. doi: 10.1177/0091217415621269
  • Kanofsky JD, Woesner ME. Clozapine-valproate adverse drug reactions and the need for a clozapine rechallenge case file. Prim Care Companion CNS Disord. 2017;19(1). doi: 10.4088/PCC.16l01968
  • De Berardis D, Fornaro M, Orsolini L, et al. Clozapine-related sudden pericarditis in a patient taking long acting aripiprazole and valproate: A case report. Clin Psychopharmacol And Neurosci. 2018;16(4):505–507. doi: 10.9758/cpn.2018.16.4.505
  • Otsuka Y, Idemoto K, Hosoda Y, et al. Clozapine-induced myocarditis: Follow-up for 3.5 years after successful retrial. J Of Gen And Family Med. 2019;20(3):114–117. doi: 10.1002/jgf2.239
  • Burns KE, Bellissima BL, Garavan F, et al. Ethnic disparity in clozapine dosing and cardiotoxicity in New Zealand. NZ Med J. 2022;135:32–40.
  • Koenig M, McCollum B, Spivey JK, et al. Four cases of myocarditis in US hospitals possibly associated with clozapine poor metabolism and a comparison with prior published cases. Neuropsychopharmacol Hung. 2022;24:29–41.
  • Müller T, Becker T, Fritze J. Neuroleptic malignant syndrome after clozapine plus carbamazepine. Lancet. 1988;332(8626–8627):1500. doi: 10.1016/S0140-6736(88)90986-5
  • Rittmannsberger H. Asterixis induced by psychotropic drug treatment. Clin Neuropharmacol. 1996;19(4):349–355. doi: 10.1097/00002826-199619040-00008
  • Wirshing WC, Ames D, Bisheff S, et al. Hepatic encephalopathy associated with combined clozapine and divalproex sodium treatment. J Clin Psychopharmacol. 1997;17(2):120–121. doi: 10.1097/00004714-199704000-00013
  • Shelly RK. Fatal pharmacokinetic interaction involving amitriptyline combined with valproate and clozapine. Irish J Psychol Med. 1998;15(3):113–114. doi: 10.1017/S0790966700003906
  • Henderson DC, Cagliero E, Gray C, et al. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatr. 2000;157(6):975–981. doi: 10.1176/appi.ajp.157.6.975
  • Nicolai J, Smith SJ, Keunen RW. Simultaneous side effects of both clozapine and valproate. Intensive care Med. 2001;27(5):943. doi: 10.1007/s001340100937
  • Egger C, Muehlbacher M, Grohmann R, et al. Clozapine intoxication in a patient with lamotrigine-induced rash. Pharmacopsychiatry. 2010;43(1):35–36. doi: 10.1055/s-0029-1239542
  • Yang SY, Liao YT, Liu HC, et al. Antipsychotic drugs, mood stabilizers, and risk of pneumonia in bipolar disorder: a nationwide case-control study. J Clin Psychiatr. 2013;74(1):e79–e86. doi: 10.4088/JCP.12m07938
  • Burk BG, Ward AH, Clark B. A case report of acute hypothermia during initial inpatient clozapine titration with review of current literature on clozapine-induced temperature dysregulations. BMC Psychiatry. 2020;20(1):290. doi: 10.1186/s12888-020-02695-w
  • Tiihonen J, Wahlbeck K, Kiviniemi V. The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2009;109(1–3):10–14. doi: 10.1016/j.schres.2009.01.002
  • Sommer IE, Begemann MJ, Temmerman A, et al. Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review. Schizophr Bull. 2012;38:1003–1011. doi: 10.1093/schbul/sbr004
  • Porcelli S, Balzarro B, Serretti A. Clozapine resistance: Augmentation strategies. Eur Neuropsychopharmacol. 2012;22(3):165–182. doi: 10.1016/j.euroneuro.2011.08.005
  • Correll CU, Maayan L, Kane J, et al. Efficacy for psychopathology and body weight and safety of topiramate-antipsychotic cotreatment in patients with schizophrenia spectrum disorders: results from a meta-analysis of randomized controlled trials. J Clin Psychiatry. 2016;77(6):e746–56. doi: 10.4088/JCP.15r10373
  • Zheng W, Xiang YT, Yang XH, et al. Clozapine Augmentation with Antiepileptic Drugs for Treatment-Resistant Schizophrenia: A Meta-Analysis of Randomized Controlled Trials. J Clin Psychiatr. 2017;78(5):e498–e505. doi: 10.4088/JCP.16r10782
  • Grover S, Sarkar S, Sahoo S. Augmentation strategies for clozapine resistance: a systematic review and meta-analysis. Acta Neuropsychiatr. 2022;35:65–75. doi: 10.1017/neu.2022.30
  • Zimbron J, Khandaker GM, Toschi C, et al. A systematic review and meta-analysis of randomised controlled trials of treatments for clozapine-induced obesity and metabolic syndrome. Eur Neuropsychopharmacol. 2016;26(9):1353–1365. doi: 10.1016/j.euroneuro.2016.07.010
  • Kim DD, Barr AM, Lu C, et al. Clozapine-associated obsessive-compulsive symptoms and their management: a systematic review and analysis of 107 reported cases. Psychother Psychosom. 2020;89(3):151–160. doi: 10.1159/000505876
  • Tohen M, Castillo J, Baldessarini RJ, et al. Blood dyscrasias with carbamazepine and valproate: a pharmacoepidemiological study of 2,228 patients at risk. Am J Psychiatry. 1995;152:413–418.
  • Vesta KS, Medina PJ. Valproic acid-induced neutropenia. Ann Pharmacother. 2003;37:819–821. doi: 10.1345/aph.1C381
  • Verdoux H, Quiles C, de Leon J. Clinical determinants of fever in clozapine users and implications for treatment management: a narrative review. Schizophr Res. 2019;211:1–9. doi: 10.1016/j.schres.2019.07.040
  • De Las Cuevas C, Sanz EJ, Ruan CJ, et al. Clozapine-associated myocarditis in the World Health Organization’s pharmacovigilance database: Focus on reports from various countries. Rev Psiquiatr Salud Ment (Engl Ed). 2022;15:238–250. doi: 10.1016/j.rpsm.2021.07.004
  • Rohde C, Polcwiartek C, Kragholm K, et al. Adverse cardiac events in out-patients initiating clozapine treatment: a nationwide register-based study*. Acta Psychiatr Scand. 2018;137(1):47–53. doi: 10.1111/acps.12827.
  • Ronaldson KJ, Fitzgerald PB, McNeil JJ. Clozapine-induced myocarditis, a widely overlooked adverse reaction. Acta Psychiatr Scand. 2015;132(4):231–240. doi: 10.1111/acps.12416
  • Pisani F, Rosa Pisani L, Barbieri MA, et al. Optimization of therapy in patients with epilepsy and psychiatric comorbidities: key points. Curr Neuropharmacol. 2023;21(8):1755–1766. doi: 10.2174/1570159X20666220526144314
  • Alper K, Schwartz KA, Kolts RL, et al. Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports. Biol Psychiatry. 2007;62(4):345–354. doi: 10.1016/j.biopsych.2006.09.023
  • Asenjo Lobos C, Komossa K, Rummel-Kluge C, et al. Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010:Cd006633. doi: 10.1002/14651858.CD006633.pub2
  • Kumlien E, Lundberg PO. Seizure risk associated with neuroactive drugs: data from the WHO adverse drug reactions database. Seizure. 2010;19(2):69–73. doi: 10.1016/j.seizure.2009.11.005
  • Reichelt L, Efthimiou O, Leucht S, et al. Second-generation antipsychotics and seizures - a systematic review and meta-analysis of serious adverse events in randomized controlled trials. Eur Neuropsychopharmacol. 2023;68:33–46. doi: 10.1016/j.euroneuro.2022.12.010
  • Ohno-Shosaku T, Sugawara Y, Muranishi C, 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
  • Rockley K, Roberts R, Jennings H, et al. An integrated approach for early in vitro seizure prediction utilizing hiPSC neurons and human ion channel assays. Toxicol Sci. 2023;196(1):126–140. doi: 10.1093/toxsci/kfad087
  • Bak TH, Bauer M, Schaub RT, et al. Myoclonus in patients treated with clozapine: a case series. J Clin Psychiatry. 1995;56:418–422.
  • Antelo RE, Stanilla JK, Martin-Llonch N. Myoclonic seizures and “leg folding” phenomena with clozapine therapy: report of two cases. Biol Psychiatry. 1994;36(11):759–762. doi: 10.1016/0006-3223(94)90087-6
  • Pacia SV, Devinsky O. Clozapine-related seizures: experience with 5,629 patients. Neurology. 1994;44(12):2247–2247. doi: 10.1212/WNL.44.12.2247
  • Hatano M, Yamada K, Matsuzaki H, et al. Analysis of clozapine-induced seizures using the Japanese adverse drug event report database. PLOS ONE. 2023;18(6):e0287122. doi: 10.1371/journal.pone.0287122
  • Simpson GM, Cooper TA. Clozapine plasma levels and convulsions. Am J Psychiatry. 1978;135:99–100.
  • Skokou M, Karavia EA, Drakou Z, et al. Adverse drug reactions in relation to clozapine plasma levels: a systematic review. Pharmaceuticals (Basel). 2022;15(7):817. doi: 10.3390/ph15070817
  • McCollum B, Barclay J, de Leon J. Unexpected falls during clozapine treatment explained by myoclonus. Prim Care Companion CNS Disord. 2018;20(1):17l02151. doi: 10.4088/PCC.17l02151
  • Verdoux H, Quiles C. Educational needs and psychoeducation interventions in clozapine users: a narrative review. Acta Psychiatr Scand. 2020;142(2):96–108. doi: 10.1111/acps.13172
  • Verdoux H, Quiles C, Bachmann CJ, et al. Prescriber and institutional barriers and facilitators of clozapine use: A systematic review. Schizophr Res. 2018;201:10–19. doi: 10.1016/j.schres.2018.05.046
  • Verdoux H, Quiles C, de Leon J. Optimizing antidepressant and clozapine co-prescription in clinical practice: a systematic review and expert recommendations. Schizophr Res. 2024;in press. doi: 10.1016/j.schres.2023.10.003
  • Verdoux H, Quiles C, de Leon J. Risks and benefits of clozapine and lithium co-prescribing: a systematic review and expert recommendations. Schizophr Res. 2024;in press. doi: 10.1016/j.schres.2023.03.032

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