Adverse effects of clozapine in older patients: Epidemiology, prevention and management

Drugs and Aging

Volumn 31, Issue 1, 2014, Pages 11-20

  Bishara, Delia ^a,b   Taylor, David ^a,b  

^a SOUTH LONDON AND MAUDSLEY NHS FOUNDATION TRUST   (United Kingdom)

^b KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ATENOLOL; ATROPINE; CARBAMAZEPINE; CLONIDINE; CLOZAPINE; CYTOCHROME P450 1A2; DESMOPRESSIN; FLUCONAZOLE; FLUOXETINE; IPRATROPIUM BROMIDE; ITRACONAZOLE; LAXATIVE; LOFEXIDINE; NORCLOZAPINE; PIRENZEPINE; RIFAMPICIN; SCOPOLAMINE; TRIHEXYPHENIDYL;

ADVERSE DRUG REACTION; AGED; AGRANULOCYTOSIS; ANAMNESIS; ARTICLE; BIPOLAR DISORDER; BLURRED VISION; BODY TEMPERATURE DISORDER; BODY WEIGHT DISORDER; CARDIOMYOPATHY; COGNITIVE DEFECT; CONFUSION; CONSTIPATION; COUGHING; DEMENTIA; DIABETES MELLITUS; DIARRHEA; DRUG INDICATION; DRUG MONITORING; DRY EYE; DYSPNEA; FECES IMPACTION; FEVER; FLU LIKE SYNDROME; GROUPS BY AGE; HEADACHE; HEART FAILURE; HUMAN; HYPERHIDROSIS; HYPERSALIVATION; HYPOTENSION; INTESTINAL DYSMOTILITY; INTESTINE OBSTRUCTION; MEMORY DISORDER; METABOLIC SYNDROME X; MICTURITION DISORDER; MYALGIA; MYOCARDITIS; NAUSEA; NEUROLEPTIC MALIGNANT SYNDROME; NEUTROPENIA; OFF LABEL DRUG USE; ORTHOSTATIC HYPOTENSION; PARALYTIC ILEUS; PARKINSON DISEASE; PRIORITY JOURNAL; PSYCHOSIS; RESTLESSNESS; SCHIZOAFFECTIVE PSYCHOSIS; SCHIZOPHRENIA; SCREENING; SEIZURE; SINUS TACHYCARDIA; SORE THROAT; TACHYCARDIA; THORAX PAIN; UNSPECIFIED SIDE EFFECT; URINE INCONTINENCE; URINE RETENTION; VOMITING;

AGED; CLOZAPINE; DRUG MONITORING; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; HUMANS;

EID: 84892915758     PISSN: 1170229X     EISSN: 11791969     Source Type: Journal    
DOI: 10.1007/s40266-013-0144-2     Document Type: Article

References (70)

1. Snowdon J, Halliday G. A study of the use of clozapine in old age psychiatry. Int Clin Psychopharmacol. 2011;26:232-5.
2. Kane J, Honigfeld G, Singer J, et al. Clozapine for the treatmentresistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45:789-96.
3. Sajatovic M, Bingham CR, Garver D, et al. An assessment of clinical practice of clozapine therapy for veterans. Psychiatr Serv. 2000;51:669-71.
4. Nolan L, O'Malley K. Prescribing for the elderly. Part I: sensitivity of the elderly to adverse drug reactions. J Am Geriatr Soc. 1988;36:142-9.
5. Van den Akker M, Buntinx F, Metsemakers JF, et al. Multimorbidity in general practice: prevalence, incidence, and determinants of co-occurring chronic and recurrent diseases. J Clin Epidemiol. 1998;51:367-75.
6. Maixner SM, Mellow AM, Tandon R. The efficacy, safety, and tolerability of antipsychotics in the elderly. J Clin Psychiatry. 1999;60(Suppl 8):29-41.
7. Lieberman JA, Saltz BL, Johns CA, et al. The effects of clozapine on tardive dyskinesia. Br J Psychiatry. 1991;158:503-10.
8. Gareri P, De Fazio P, Russo E, et al. The safety of clozapine in the elderly. Expert Opin Drug Saf. 2008;7:525-38.
9. Khan AY, Preskorn SH. Examining concentration-dependent toxicity of clozapine: role of therapeutic drug monitoring. J Psychiatr Pract. 2005;11:289-301.
10. Meltzer HY. An overview of the mechanism of action of clozapine. J Clin Psychiatry. 1994;55 Suppl B:47-52.
11. Praharaj SK, Arora M, Gandotra S. Clozapine-induced sialorrhea: pathophysiology and management strategies. Psychopharmacology. 2006;185:265-73.
12. Pitner JK, Mintzer JE, Pennypacker LC, et al. Efficacy and adverse effects of clozapine in four elderly psychotic patients. J Clin Psychiatry. 1995;56:180-5.
13. Chengappa KN, Baker RW, Kreinbrook SB, et al. Clozapine use in female geriatric patients with psychoses. J Geriatr Psychiatry Neurol. 1995;8:12-5.
14. Shulman RW, Singh A, Shulman KI. Treatment of elderly institutionalized bipolar patients with clozapine. Psychopharmacol Bull. 1997;33:113-8.
15. Sajatovic M, Madhusoodanan S, Coconcea N. Managing bipolar disorder in the elderly: defining the role of the newer agents. Drugs Aging. 2005;22:39-54.
16. The Parkinson Study Group. Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson's disease. N Engl J Med. 1999;340:757-63.
17. Frieling H, Hillemacher T, Ziegenbein M, et al. Treating dopamimetic psychosis in Parkinson's disease: structured review and meta-analysis. Eur Neuropsychopharmacol. 2007;17:165-71.
18. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:146-56.
19. Turnheim K. When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly. Exp Gerontol. 2003;38:843-53.
20. Novartis Pharmaceuticals UK Limited. Summary of product characteristics [pamphlet]. Clozaril 25 mg and 100 mg tablets; 2013. http://www.medicines.org. uk/emc/medicine/1277/SPC/Clozaril?25mg?and?100mg?Tablets/. Accessed 3 Dec 2013.
21. Wooten JM. Pharmacotherapy considerations in elderly adults. South Med J. 2012;105:437-45.
22. Alvir JM, Lieberman JA, Safferman AZ, et al. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med. 1993;329:162-7.
23. Herst L, Powell G. Is clozapine safe in the elderly? Aust N Z J Psychiatry. 1997;31:411-7.
24. Sweet RA, Pollock BG. New atypical antipsychotics: experience and utility in the elderly. Drugs Aging. 1998;12:115-27.
25. Young CR, Bowers MB Jr, Mazure CM. Management of the adverse effects of clozapine. Schizophr Bull. 1998;24:381-90.
26. Manu P, Sarpal D, Muir O, et al. When can patients with potentially life-threatening adverse effects be rechallenged with clozapine? A systematic review of the published literature. Schizophr Res. 2012;134:180-6.
27. Malone M, Carnahan RM, Kutscher EC. Antipsychotic medication use in the elderly patient. J Pharm Pract. 2007;20:318-26.
28. Ronaldson KJ, Fitzgerald PB, Taylor AJ, et al. A new monitoring protocol for clozapine-induced myocarditis based on an analysis of 75 cases and 94 controls. Aust N Z J Psychiatry. 2011;45: 458-65.
29. Wehmeier PM, Heiser P, Remschmidt H. Myocarditis, pericarditis and cardiomyopathy in patients treated with clozapine. J Clin Pharm Ther. 2005;30:91-6.
30. Rostagno C, DiNG, Placidi GF, et al. Beta-blocker and angiotensinconverting enzyme inhibitor may limit certain cardiac adverse effects of clozapine. Gen Hosp Psychiatry. 2008;30:280-3.
31. Byerly MJ, Weber MT, Brooks DL, et al. Antipsychotic medications and the elderly: effects on cognition and implications for use. Drugs Aging. 2001;18:45-61.
32. The French Clozapine Parkinson Study Group. Clozapine in drug-induced psychosis in Parkinson's disease. Lancet. 1999;353:2041-2.
33. Musser WS, Akil M. Clozapine as a treatment for psychosis in Parkinson's disease: A review. J Neuropsychiatry Clin Neurosci. 1996;8:1-9.
34. Burke WJ, Pfeiffer RF, McComb RD. Neuroleptic sensitivity to clozapine in dementia with Lewy bodies. J Neuropsychiatry Clin Neurosci. 1998;10:227-9.
35. Rajji TK, Uchida H, Ismail Z, et al. Clozapine and global cognition in schizophrenia. J Clin Psychopharmacol. 2010;30:431-6.
36. Li Z, Huang M, Ichikawa J, et al. N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarinic receptors. Neuropsychopharmacology. 2005;30:1986-95.
37. Rege S, Lafferty T. Life-threatening constipation associated with clozapine. Austral Psychiatry. 2008;16:216-9.
38. Palmer SE, McLean RM, Ellis PM, et al. Life-threatening clozapine- induced gastrointestinal hypomotility: an analysis of 102 cases. J Clin Psychiatry. 2008;69:759-68.
39. Aarsland D, Perry R, Larsen JP, et al. Neuroleptic sensitivity in Parkinson's disease and parkinsonian dementias. J Clin Psychiatry. 2005;66:633-7.
40. Frankenburg FR, Kalunian D. Clozapine in the elderly. J Geriatr Psychiatry Neurol. 1994;7:129-32.
41. Lieberman JA. Maximizing clozapine therapy: managing side effects. J Clin Psychiatry. 1998;59:38-43.
42. Stryjer R, Timinsky I, Reznik I, et al. Beta-adrenergic antagonists for the treatment of clozapine-induced sinus tachycardia: A retrospective study. Clin Neuropharmacol. 2009;32:290-2.
43. Hagg S, Spigset O, Bate A, et al. Myocarditis related to clozapine treatment. J Clin Psychopharmacol. 2001;21:382-8.
44. Naranjo CA, Herrmann N, Mittmann N, et al. Recent advances in geriatric psychopharmacology. Drugs Aging. 1995;7:184-202.
45. Varma S, Bishara D, Besag FMC, et al. Clozapine-related EEG changes and seizures: dose and plasma-level relationships. Ther Adv Psychopharmacol. 2011;1:47-66.
46. Ball CJ. The use of clozapine in older people. Int J Geriatr Psychiatry. 1992;7:689-92.
47. Lieberman JA, Safferman AZ. Clinical profile of clozapine: adverse reactions and agranulocytosis. Psychiatr Q. 1992;63:51-70.
48. Guith DM. Clozapine: serious adverse side effects, drug interactions, and other complications of therapy. J Pharm Pract. 1996;9:118-29.
49. Iqbal MM, Rahman A, Husain Z, et al. Clozapine: A clinical review of adverse effects and management. Ann Clin Psychiatry. 2003;15:33-48.
50. Davydov L, Botts SR. Clozapine-induced hypersalivation. Ann Pharmacother. 2000;34:662-5.
51. Sockalingam S, Shammi C, Remington G. Clozapine-induced hypersalivation: A review of treatment strategies. Can J Psychiatry. 2007;52:377-84.
52. Sockalingam S, Shammi C, Remington G. Treatment of clozapine- induced hypersalivation with ipratropium bromide: A randomized, double-blind, placebo-controlled crossover study. J Clin Psychiatry. 2009;70:1114-9.
53. Fritze J, Elliger T. Pirenzepine for clozapine-induced hypersalivation. Lancet. 1995;346:1034.
54. Bai YM, Lin CC, Chen JY, et al. Therapeutic effect of pirenzepine for clozapine-induced hypersalivation: A randomized, double-blind, placebo-controlled, cross-over study. J Clin Psychopharmacol. 2001;21:608-11.
55. Schneider B, Weigmann H, Hiemke C, et al. Reduction of clozapine- induced hypersalivation by pirenzepine is safe. Pharmacopsychiatry. 2004;37:43-5.
56. Fuller MA, Borovicka MC, Jaskiw GE, et al. Clozapine-induced urinary incontinence: incidence and treatment with ephedrine. J Clin Psychiatry. 1996;57:514-8.
57. Sarma S, Ward W, O'Brien J, et al. Severe hyponatraemia associated with desmopressin nasal spray to treat clozapineinduced nocturnal enuresis. Aust N Z J Psychiatry. 2005;39:949.
58. Malhi G, Adams D, Plain J, et al. Clozapine and cardiometabolic health in chronic schizophrenia: correlations and consequences in a clinical context. Austral Psychiatry. 2010;18:32-41.
59. Henderson DC, Cagliero E, Gray C, et al. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry. 2000;157:975-81.
60. Holt R. The metabolic side-effects of antipsychotics in elderly patients. Geriatr Med. 2008;38:399-402.
61. Meltzer HY. Illuminating the molecular basis for some antipsychotic drug-induced metabolic burden. Proc Natl Acad Sci U S A. 2007;104:3019-20.
62. Melkersson K, Dahl ML. Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications. Drugs. 2004;64:701-23.
63. Taylor D, Paton C, Kapur S. Maudsley prescribing guidelines in psychiatry. 11th ed. Oxford: Wiley-Blackwell; 2012.
64. Bowskill S, Couchman L, MacCabe JH, et al. Plasma clozapine and norclozapine in relation to prescribed dose and other factors in patients aged 65 years and over: data from a therapeutic drug monitoring service, 1996-2010. Hum Psychopharmacol. 2012;27:277-83.
65. Ismail Z, Wessels AM, Uchida H, et al. Age and sex impact clozapine plasma concentrations in inpatients and outpatients with schizophrenia. Am J Geriatr Psychiatry. 2012;20:53-60.
66. Tang YL, Mao P, Li FM, et al. Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia. Br J Clin Pharmacol. 2007;64:49-56.
67. Ng CH, Chong SA, Lambert T, et al. An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels. Int Clin Psychopharmacol. 2005;20:163-8.
68. Rostami-Hodjegan A, Amin AM, Spencer EP, et al. Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: A predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients. J Clin Psychopharmacol. 2004;24:70-8.
69. Spina E, de LJ. Metabolic drug interactions with newer antipsychotics: A comparative review. Basic Clin Pharmacol Toxicol. 2007;100:4-22.
70. Sajatovic M, Jaskiw G, Konicki PE, et al. Outcome of clozapine therapy for elderly patients with refractory primary psychosis. Int J Geriatr Psychiatry. 1997;12:553-8.