Clozapine is a second-generation antipsychotic drug, proven to be effective in treatment-resistant schizophrenia. Among patients using clozapine; the incidence of neutropenia is approximately 3% and the incidence of agranulocytosis is approximately 1%. This side effect is diminishing after 18 weeks of drug initiation. Here, we present a case of clozapine-induced neutropenia in a schizophrenic patient seen after 7 years of clozapine use and its treatment with lithium supplementation.
___
Rajagopal S. Clozapine, agranulocytosis and benign ethnic neutropenia. Postgrad Med J 2005; 81:545-546.
Myles N, Myles H, Xia S, Large M, Kisely S, Galletly C, Bird R, Siskind D. Meta-analysis examining the epidemiology of clozapine-associated neutropenia. Acta Psychiatr Scand 2018; 138:101-109.
Simon L, Cazard F. Clozapine rechallenge after neutropenia in resistant schizophrenia: a review. Encephale 2016; 42:346-353. (French)
Meyer N, Gee S, Whiskey E, Taylor D, Mijovic A, Gaughran F, Shergill S, MacCabe JH. Optimizing outcomes in clozapine rechallenge following neutropenia: a cohort analysis. J Clin Psychiatry 2015; 76:e1410-e1416.
Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med 1993; 329:162-167.
Dunk LR, Annan LJ, Andrews CD. Rechallenge with clozapine following leucopenia or neutropenia during previous therapy. Br J Psychiatry 2006; 188:255-263.
Ghaznavi S, Nakic M, Rao P, Hu J, Brewer JA, Hannestad J, Bhagwagar Z. Rechallenging with clozapine following neutropenia: treatment options for refractory schizophrenia. Am J Psychiatry 2008; 165:813-818.
Cohen D, Monden M. White blood cell monitoring during longterm clozapine treatment. Am J Psychiatry 2013; 170:366-369.
Patel NC, Dorson PG, Bettinger TL. Sudden late onset of clozapine-induced agranulocytosis. Ann Pharmacother 2002; 36:1012-1015.
Raja M, Azzoni A, Maisto G. Late onset neutropenia associated with clozapine. J Clin Psychopharmacol 2011; 31:780-781.
Brunoni AR, Kobuti Ferreira LR, Gallucci-Neto J, Elkis H, Velloso ED, Vinicius Zanetti M. Lithium as a treatment of clozapineinduced neutropenia: a case report. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32:2006-2007.
Sporn A, Gogtay N, Ortiz-Aguayo R, Alfaro C, Tossell J, Lenane M, Gochman P, Rapoport JL. Clozapine-induced neutropenia in children: management with lithium carbonate. J Child Adolesc Psychopharmacol 2003; 13:401-404.
Suraweera C, Hanwella R, de Silva V. Use of lithium in clozapineinduced neutropenia: a case report. BMC Res Notes 2014; 7:635.
Hazewinkel AW, Bogers JP, Giltay EJ. Add-on filgrastim during clozapine rechallenge unsuccessful in preventing agranulocytosis. Gen Hosp Psychiatry 2013; 35:576e11-576e12.
Khan AA, Harvey J, Sengupta S. Continuing clozapine with granulocyte colony-stimulating factor in patients with neutropenia. Ther Adv Psychopharmacol 2013; 3:266-271.
Lally J, Malik S, Whiskey E, Taylor DM, Gaughran FP, Krivoy A, Flanagan RJ, Mijovic A, MacCabe JH. Clozapine-associated agranulocytosis treatment with granulocyte colony-stimulating factor/granulocyte-macrophage colony stimulating factor: A systematic review. J Clin Psychopharmacol 2017; 37:441-446.
Myles N, Myles H, Clark SR, Bird R, Siskind D. Use of granulocytecolony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations. Aust N Z J Psychiatry 2017; 51:980-989.
Tigue CC, McKoy JM, Evens AM, Trifilio SM, Tallman MS, Bennett CL. Granulocyte-colony stimulating factor administration to healthy individuals and persons with chronic neutropenia or cancer: an overview of safety considerations from the Research on Adverse Drug Events and Reports project. Bone Marrow Transplant 2007; 40:185-192.
Paton C, Esop R. Managing clozapine-induced neutropenia with lithium. Psychiatric Bulletin 2005; 29:186-188.
Rosli ANM, Subbiah R, Maniam T. Clozapine re-challenge with lithium supplementation following clozapine-induced neutropenia. ASEAN Journal of Psychiatry 2014; 15:90-92.
Dumas R, Bardin P, Vedie C. Long-term treatment of clozapineinduced leukopenia with lithium: fast-onset agranulocytosis following lithium discontinuation. Prim Care Companion CNS Disord 2016; 18:1.
Lapierre G, Stewart RB. Lithium carbonate and leukocytosis. Am J Hosp Pharm 1980; 37:1525-1528.
Blier P, Slater S, Measham T, Koch M, Wiviott G. Lithium and clozapine-induced neutropenia/agranulocytosis. Int Clin Psychopharmacol 1998; 13:137-140.
Pinninti NR, Houdart MP, Strouse EM. Case report of longterm lithium for treatment and prevention of clozapineinduced neutropenia in an African American male. J Clin Psychopharmacol 2010; 30:219-221.
Aydin M, Ilhan BC, Calisir S, Yildirim S, Eren I. Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports. Ther Adv Psychopharmacol 2016; 6:33-38.