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Clozapine and blood dyscrasia

  • Zahid Latif (a1), Faraz Jabbar (a2) and Brendan D. Kelly (a2)


Clozapine is an effective antipsychotic medication but is associated with agranulocytosis, neutropenia and leucopenia. The reintroduction of clozapine improved management of treatment-resistant schizophrenia, yet resulted in a paradoxical situation whereby the risk of blood dyscrasias is rigorously managed but other adverse effects (e.g. seizures, cardiovascular complications) are less well monitored. Monitoring of weight, lipids, plasma glucose and other metabolic parameters is recommended. There is also a need to reconsider routine haematological monitoring with other medications associated with blood dyscrasia (e.g. phenothiazines, carbamazepine). In particular, individuals who develop clozapine-induced blood dyscrasia may require haematological monitoring during treatment with other antipsychotics.

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1 Crilly, J. The history of clozapine and its emergence in the US market: a review and analysis. Hist Psychiatry 2009; 18;3960.
2 Kane, J, Honigfeld, G, Singer, J, Meltzer, H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988; 45: 789–96.
3 Pirmohamed, M, Park, K. Mechanism of clozapine-induced agranulocytosis. CNS Drugs 1997; 7: 139158.
4 Gerson, SL. Clozapine – deciphering the risks. N Engl J Med 1993; 329: 204–5.
5 Gerson, SL. G-CSF and the management of clozapine-induced agranulocytosis. J Clin Psychiatry 1994; 55: 139–42.
6 Atkin, K, Kendall, F, Gould, D, Freeman, H, Lieberman, J, O'Sullivan, D. Neutropenia and agranulocytosis in patients receiving clozapine in the UK and Ireland. Br J Psychiatry 1996; 169: 483–8.
7 Dunk, LR, Annan, LJ, Andrews, CD. Rechallenge with clozapine following leucopenia or neutropenia during previous therapy. Br J Psychiatry 2006; 188: 255–63.
8 Munro, J, O'Sullivan, D, Andrews, C, Arana, A, Mortimer, A, Kerwin, R. Active monitoring of 12760 clozapine recipients in the UK and Ireland: beyond pharmacovigilance. Br J Psychiatry 1999; 175: 576–80.
9 Kelly, DL, Kreyenbuhl, J, Dixon, L, Love, RC, Medoff, D, Conley, RR. Clozapine underutilization and discontinuation in African Americans due to leucopenia. Schizophr Bull 2007; 33: 1221–4.
10 Williams, DP, Pirmohamed, M, Naisbitt, DJ, Maggs, JL, Park, BK. Neutrophil cytotoxicity of the chemically reactive metabolite(s) of clozapine: possible role in agranulocytosis. J Pharmacol Exp Ther 1997; 283: 1375–82.
11 Sackett, DL, Rosenberg, WM, Gray, JA, Haynes, RB, Richardson, WS. Evidence based medicine: what it is and what it isn't. BMJ 1996; 312: 71–2.
12 Esposito, D, Hardy, P, Corruble, E. Clozapine treatment following blood dyscrasia. Br J Psychiatry 2006; 189: 186.
13 Ghaznavi, S, Nakic, M, Rao, P, Hu, J, Brewer, JA, Hannestad, J, Bhagwagar, Z. Rechallenge with clozapine following neutropenia: treatment options for refractory schizophrenia. Am J Psychiatry 2008; 165: 813–8.
14 Taylor, D, Paton, C, Kapur, S. The South London and Maudsley NHS Foundation Trust and Oxleas NHS Foundation Trust Prescribing Guidelines (10th edn). Informa Healthcare, 2009.
15 Whiskey, E, Taylor, D. Restarting clozapine after neutropenia: evaluating the possibilities and practicalities. CNS Drugs 2007; 21: 2535.
16 Dernovsek, Z, Tavcar, R. Risperidone induced leucopenia and neutropenia. Br J Psychiatry 1997; 171: 393–4.
17 Thangadurai, P, Jyothi, KS, Gopalakrishnan, R, Kuruvilla, A, Jacob, KS. Reversible neutropenia with olanzapine following clozapine-induced neutropenia. Am J Psychiatry 2006; 163: 1298.


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Clozapine and blood dyscrasia

  • Zahid Latif (a1), Faraz Jabbar (a2) and Brendan D. Kelly (a2)
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Rebound psychosis following Clozapine withdrawal

Dumindu Witharana, Honorary Specialist Registrar in Forensic Psychiatry
21 January 2011

Latif et al (1) address the crucial issue of blood dyscrasias associated with clozapine. Although they quite rightly mention that this is one aspect of a range of adverse effects (including seizures and cardiovascular complications), we would like to draw the reader’s attention to a less well emphasised but nevertheless important issue, variously termed clozapine withdrawal, discontinuation or rebound psychosis. This phenomenon may perhaps be neglected because, paradoxically, it may emerge after patients have suddenly stopped taking clozapine, and therefore does not comfortably fit into the category of ‘adverse effects’. Indeed, terms such as withdrawal and discontinuation have also led this phenomenon to be addressed within the addictions literature.

Emergence of a rapid ‘supersensitivity psychosis’ following sudden withdrawal of clozapine has been well documented in the literature (2) ; various studies have attributed rapid relapse following clozapine withdrawal to clozapine induced supersentivity for dopamine, acetylcholineor serotonin receptors (3). Seppala et al (4) found a rapid deterioration in mental state following withdrawal in almost half the patients of a group who had been on long term clozapine treatment and, according to Seeman and Tallerico (3) , the rate of psychotic relapse in patients withdrawn from clozapine is five times higher than that for a traditional antipsychotic such as haloperidol or flupenthixol. Clozapine withdrawal psychosis has also been observed to be severe in symptomatology and in some cases associated with delirium (5).

It is certainly not uncommon for clinicians to see patients suffer a severe rebound psychosis as a result of sudden clozapine withdrawal. Emphasis has rightly been placed on preventing a sudden discontinuation ofother psychiatric medications with the potential of precipitating a rebound illness (e.g. lithium ) by educating patients. Unfortunately, in our experience, this does not necessarily extend to clozapine.

In our opinion, patients should be made aware of the risks of sudden discontinuation of clozapine treatment, including the possibility of severe symptomatology, at the treatment planning stage with a clear care plan to manage a rebound illness in the event of a sudden discontinuation.From a medicolegal perspective, given that rebound psychosis cannot be considered rare, a clear explanation of the phenomenon during the consent to treatment interview should form a crucial part of obtaining informed consent before prescribing clozapine.


1 Latif Z, Jabbar F, Kelly BD. Clozapine and blood dyscrasia. The Psychiatrist 2010; 35: 27-30.

2 Ekblom B, Eriksson K, Lindström LH. Supersensitivity psychosis inschizophrenic patients after sudden clozapine withdrawal. Psychopharmacology 1984; 83: 293–294.

3 Seeman P, Tallerico T. Rapid Release of Antipsychotic Drugs From Dopamine D2 Receptors: An Explanation for Low Receptor Occupancy and EarlyClinical Relapse Upon Withdrawal of Clozapine or Quetiapine. Am J Psychiatry 1999; 156:876-84.

4 Seppala N, Kovio C, Leinonen E. Effect of anticholinergics in preventing acute deterioration in patients undergoing abrupt Clozapine withdrawal. CNS Drugs 2005; 19: 1049-55.

5 Stanilla JK, De Leon J, Simpson GM. Clozapine withdrawal resultingin delirium with psychosis: a report of three cases. J Clin Psychiatry 1997; 58:252–255.

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