“Schizophrenia past Clozapine”: Reasons for Clozapine Discontinuation, Mortality, and Alternative Antipsychotic Prescribing

Abstract

Introduction: The clinical records of 190 patients with schizophrenia who discontinued clozapine between 1990 and 2012 in the county of Northamptonshire were examined, in an attempt to answer the following questions. Why do patients stop clozapine? What do physicians prescribe as an alternative? What is the mortality in this patient group?

Methods: Patients’ data were extracted using their electronic records, then analysed using descriptive statistical methods.

Results: Non-compliance with treatment, or with the mandatory white blood cell monitoring, was the most common reason (55.3%) for clozapine cessation, followed by neutropaenia and other adverse effects (25.2%). Death (mean age 48 years) was the third most common reason (10%), with respiratory infections accounting for more than a quarter of the deaths. 13% of the patients had died (mean age 49 years) at some point following clozapine discontinuation. In terms of the alternative antipsychotic prescribing, olanzapine was the most commonly prescribed (37.1%) drug in patients who were still under the care of the local psychiatric service (n=121), at the time of data extraction. Clozapine had been reinstated in 19% of these patients.

Discussion: Our findings are generally consistent with previous studies, and they demonstrate the need for physicians to address their patients’ concerns regarding clozapine treatment, and to effectively manage any adverse effects. Sialorrhea and constipation seem to be particularly of concern, as they may be linked to clozapine– related mortality. Olanzapine was the most commonly prescribed alternative to clozapine, which suggests that it may possibly have a role in refractory schizophrenia.

Key words

schizophrenia past clozapine - clozapine discontinuation - clozapine mortality - alternative to clozapine - olanzapine

• References

• 1 Kane J, Honigfeld G, Singer J et al. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988; 45: 789-796
• 2 McEvoy JP, Lieberman JA, Stoup TS et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006; 163: 600-610
• 3 Buchanan RW. Clozapine: efficacy and safety. Schizophr Bull 1995; 21: 579-591
• 4 Mustafa FA. Schizophrenia past clozapine: what works?. J Clin Psychopharmacol 2013; 33: 63-68
• 5 Davis MC, Fuller MA, Strauss ME et al. A 15-year naturalistic retrospective study of 320 patients. Acta Psychiatr Scand 2013; DOI: 10.1111/acps.12233.
• 6 Pai NB, Vella SC. Reason for clozapine cessation. Acta Psychiatr Scand 2012; 125: 39-44
• 7 Taylor DM, Douglas-Hall P, Olofinjana B et al. Reasons for discontinuing clozapine: matched, case-control comparison with risperidone long-acting injection. Br J Psychiatry 2009; 194: 165-167
• 8 Bastiampillai T, Avina P, Malalagama G et al. 2012; Gender differences in clozapine prescription in Australia. Curr Psychopharmacol 2012; 6 111-116
• 9 Mustafa F, Abdelmawla N, Chikodzore LMD et al. Gender differences in clozapine prescription for patients with treatment resistant schizophrenia: A case note survey. J Psychopharmacol 2009; (Suppl. 23) 6: A60
• 10 Meltzer HY. Clozapine: balancing safety with superior antipsychotic efficacy. Clin Schizophr Relat Psychoses 2012; 6: 134-144
• 11 Tiihonen J, Lönnqvist J, Wahlbeck K et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009; 374: 620-627
• 12 Hinkes R, Quesada TV, Currier MB et al. Aspiration pneumonia possibly secondary to clozapine-induced sialorrhea. J Clin Psychopharmacol 1996; 16: 462-463
• 13 Maddalena AS, Fox M, Hofmann M et al. Esophageal dysfunction on psychotropic medication. A case report and literature review. Pharmacopsychiatry 2004; 37: 134-138
• 14 Levin TT, Barrett J, Mendelowitz A. Death from clozapine-induced constipation: case report and literature review. Psychosomatics 2002; 43: 71-73
• 15 Hayes G, Gibler B. Clozapine-induced constipation. Am J Psychiatry 1995; 152: 298
• 16 Wahlbeck K, Westman J, Nordentoft M et al. Outcomes of Nordic mental health systems: life expectancy of patients with mental disorders. Br J Psychiatry 2011; 199: 453-458
• 17 Crump C, Winkleby MA, Sundquist K et al. Comorbidities and mortality in persons with schizophrenia: a Swedish national cohort study. Am J Psychiatry 2013; 170: 324-333
• 18 Chakos M, Lieberman J, Hoffman E et al. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry 2001; 158: 518-526
• 19 Leucht S, Tardy M, Komossa K et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 2012; 379: 2063-2071
• 20 Remington G, Agid O, Foussias G et al. Clozapine’s role in the treatment of first-episode schizophrenia. Am J Psychiatry 2013; 170: 146-151