Hostname: page-component-848d4c4894-x24gv Total loading time: 0 Render date: 2024-06-01T08:17:13.130Z Has data issue: false hasContentIssue false
  • English
  • Français

A systematic review of clozapine’s effectiveness for primary psychotic and bipolar disorders in older adults

Published online by Cambridge University Press:  22 February 2021

Melissa Renzenbrink  and
Anne Pamela Frances Wand Open the ORCID record for Anne Pamela Frances Wand [Opens in a new window]
Melissa Renzenbrink*
Affiliation:
Older Persons’ Mental Health Service, Concord Centre for Mental Health, Concord, Sydney, New South Wales, Australia
Anne Pamela Frances Wand
Affiliation:
Older Persons’ Mental Health Service, Concord Centre for Mental Health, Concord, Sydney, New South Wales, Australia Specialty of Psychiatry, Faculty of Medicine and Health, University of Sydney, Sydney, Australia School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia
*
Correspondence should be addressed to: Melissa Renzenbrink, Jara Unit, Concord Centre for Mental Health, Hospital Rd, Concord, NSW, 2139, Australia. Phone + 61 297 678 940; Fax: + 61 297 678 944. Email: melissa.renzenbrink@health.nsw.gov.au.
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives:

The primary aim was to systematically review the literature regarding the effectiveness of clozapine in reducing symptoms of primary psychotic and bipolar disorders in older adults. The secondary aim was to describe other reported patient and caregiver outcomes of clozapine treatment in older adults.

Design:

MEDLINE, Embase, PsychINFO, ProQuest, and PubMed databases were searched according to PRISMA guidelines for original empirical research examining the effectiveness of clozapine in adults aged 65 years or more with primary psychotic and bipolar disorders. Identified studies were assessed for methodological quality using the QualSyst tool.

Results:

1121 records were screened, of which 7 studies met the inclusion criteria. In total, 128 subjects participated in the included studies (111 of whom were from a single study), with an age range of 65–86 years, and diagnoses including schizophrenia, schizoaffective disorder, bipolar disorder, and delusional disorder. Indications for clozapine use included treatment resistance and inability to tolerate other treatments. While six out of seven studies reported some improvement on the primary measure of psychopathology after treatment with clozapine, the group effects were modest and based on low-level evidence. Additional reported outcomes included discharge destination, death, and relapse. Most of the included studies were only of adequate methodological quality, with significant risks of bias identified.

Conclusions:

Clozapine may have positive effects for primary psychotic and bipolar illnesses in some older adults, but the group effects reported were modest and based on low-level evidence studies with methodological limitations. Based on these findings, clinical decision-making about whether or not to trial clozapine should involve an individualized analysis of potential benefits and risks in collaboration with patients and their families and caregivers.

Keywords

delusional disorderefficacyoutcomespsychosisschizophreniaschizoaffective disorder
Type
Review Article
Information
International Psychogeriatrics , Volume 34 , Special Issue 10: Issue Theme: Pharmacotherapy for Serious Neuropsychiatric Disorders , October 2022 , pp. 875 - 887
Copyright
© International Psychogeriatric Association 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adams, R. J., Smart, P. and Huff, A. S. (2017). Shades of grey: guidelines for working with the grey literature in systematic reviews for management and organizational studies. International Journal of Management Reviews, 19, 432–454. doi: 10.1111/ijmr.12102.CrossRefGoogle Scholar
Asenjo Lobos, C. et al. (2010). Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews, 11, CD006633. doi: 10.1002/14651858.CD006633.pub2.Google Scholar
Bajulaiye, R. and Addonizio, G. (1992). Clozapine in the treatment of psychosis in an 82-year-old woman with tardive dyskinesia. Journal of Clinical Psychopharmacology, 12, 364–365. doi: 10.1016/S0010-440X(99)90134-7 Google Scholar
Ball, C. J. (1992). The use of clozapine in older people. International Journal of Geriatric Psychiatry, 7, 689–692. doi: 10.1002/gps.930070912.CrossRefGoogle Scholar
Barak, Y., Wittenberg, N., Naor, S., Kutzuk, D. and Weizman, A. (1999). Clozapine in elderly psychiatric patients: tolerability, safety, and efficacy. Comprehensive Psychiatry, 40, 320–325. doi: 10.1016/S0010-440X(99)90134-7.CrossRefGoogle ScholarPubMed
Bishara, D. and Taylor, D. (2014). Adverse effects of clozapine in older patients: epidemiology, prevention and management. Drugs & Aging, 31, 11–20. doi: 10.1007/s40266-013-0144-2.CrossRefGoogle Scholar
Buckley, P. F., Sajatovic, M. and Meltzer, H. Y. (1994). Treatment of delusional disorders with clozapine. American Journal of Psychiatry, 151, 1394–1395. doi: 10.1176/ajp.151.9.1394.Google ScholarPubMed
Calabrese, J. R. et al. (1996). Clozapine for treatment-refractory mania. American Journal of Psychiatry, 153, 759–764. doi: 10.1176/ajp.153.6.759.Google ScholarPubMed
Chengappa, K. N. R., Baker, R. W., Kreinbrook, S. B. and Adair, D. (1995). Clozapine use in female geriatric patients with psychoses. Journal of Geriatric Psychiatry and Neurology, 8, 12–15.Google ScholarPubMed
Cho, J. et al. (2018). Clozapine and all-cause mortality in treatment-resistant schizophrenia: a historical cohort study. Acta Psychiatrica Scandinavica, 139, 237–247. doi: 10.1111/acps.12989.Google ScholarPubMed
Cohen, C., Meesters, P. and Zhao, J. (2015). New perspectives on schizophrenia in later life: implications for treatment, policy, and research. Lancet Psychiatry, 2, P340–P350. doi: 10.1016/S2215-0366(15)00003-6.CrossRefGoogle Scholar
Correll, C., Kishimoto, T., Nielsen, J. and Kane, J. (2011). Quantifying clinical relevance in the treatment of schizophrenia. Clinical Therapeutics, 33, B16–B39. doi: 10.1016/j.clinthera.2011.11.016.CrossRefGoogle ScholarPubMed
De Berardis, D. et al. (2018). Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine. Therapeutic Advances in Drug Safety, 9, 237–256. doi: 10.1177/2042098618756261.CrossRefGoogle ScholarPubMed
Essali, A., Al-Haj Hassan, N., Li, C. and Rathbone, J. (2009). Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database of Systematic Reviews, 1, CD000059. doi: 10.1002/14651858.CD000059.pub2.Google Scholar
Fitzsimmons, J., Berk, M., Lambert, T., Bourin, M. and Dodd, S. (2005). A review of clozapine safety. Expert Opinion on Drug Safety, 4, 731–744. doi: 10.1517/14740338.4.4.731.CrossRefGoogle Scholar
Frankenburg, F. R. and Kalunian, D. (1994). Clozapine in the elderly. Journal of Geriatric Psychiatry and Neurology, 7, 129–132. doi: 10.1177/089198879400700209.CrossRefGoogle ScholarPubMed
Frogley, C., Taylor, D., Dickens, G. and Picchioni, M. (2012). A systematic review of the evidence of clozapine’s anti-aggressive effects. International Journal of Neuropsychopharmacology, 15, 1351–1371. doi: 10.1017/S146114571100201X.CrossRefGoogle ScholarPubMed
Frye, M. A., Altshuler, L. L. and Bitran, J. A. (1996). Clozapine in rapid cycling bipolar disorder. Journal of Clinical Psychopharmacology, 16, 87–90. doi: 10.1097/00004714-199602000-00022.CrossRefGoogle ScholarPubMed
Galletly, C. et al. (2016). Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Australian and New Zealand Journal of Psychiatry, 50, 1–117. doi: 10.1177%2F0004867416641195.CrossRefGoogle ScholarPubMed
Gareri, P., De Fazio, P., Russo, E., Marigliano, N., De Fazio, S. and De Sarro, G. (2008). The safety of clozapine in the elderly. Expert Opinion on Drug Safety, 7, 525–538. doi: 10.1517/14740338.7.5.525.CrossRefGoogle ScholarPubMed
Herrera, A., Snipes, S., King, D., Torres-Vigil, I., Goldberg, D. and Weinberg, A. (2010). Disparate inclusion of older adults in clinical trials: priorities and opportunities for policy and practice change. American Journal of Public Health, 100, S105–S112. doi: 10.2105/AJPH.2009.162982.CrossRefGoogle ScholarPubMed
Herst, L. and Powell, G. (1997). Is clozapine safe in the elderly? Australian and New Zealand Journal of Psychiatry, 31, 411–417. doi: 10.3109/00048679709073852.CrossRefGoogle ScholarPubMed
Howanitz, E. et al. (1999). The efficacy and safety of clozapine versus chlorpromazine in geriatric schizophrenia. Journal of Clinical Psychiatry, 60, 41–44. doi: 10.4088/jcp.v60n0109.CrossRefGoogle ScholarPubMed
Kmet, L., Lee, R. and Cook, L. (2004). Standard quality assessment criteria for evaluating primary research papers from a variety of fields [Online]. Available at: https://www.ihe.ca/publications/standard-quality-assessment-criteria-for-evaluating-primary-research-papers-from-a-variety-of-fields; last accessed 20 July 2020.Google Scholar
Land, R., Siskind, D., McArdle, P., Kisely, S., Winckel, K. and Hollingworth, S. (2017). The impact of clozapine on hospital use: a systematic review and meta-analysis. Acta Psychiatrica Scandinavica, 135, 296–309. doi: 10.1111/acps.12700.CrossRefGoogle ScholarPubMed
Laursen, T. (2011). Life expectancy among persons with schizophrenia or bipolar affective disorder. Schizophrenia Research, 131, 101–104. doi: 10.1016/j.schres.2011.06.008.CrossRefGoogle ScholarPubMed
Law, A. and Croucher, M. (2019). Prescribing trends and safety of clozapine in an older persons mental health population. International Psychogeriatrics, 31, 1823–1829. doi: 10.1017/S1041610219000255.CrossRefGoogle Scholar
Lee, L., Packer, T., Tang, S. and Girdler, S. (2008). Self-management education programs for age-related macular degeneration: a systematic review. Australasian Journal of Ageing, 27, 170–176. doi: 10.1111/j.1741-6612.2008.00298.x.CrossRefGoogle ScholarPubMed
Leucht, S. et al. (2013). Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. The Lancet, 382, 951–962. doi: 10.1016/S0140-6736(13)60733-3.CrossRefGoogle ScholarPubMed
Leucht, S., Kane, J. M., Kissling, W., Hamann, J., Etschel, E. and Engel, R. (2005). Clinical implications of Brief Psychiatric Rating Scale scores. British Journal of Psychiatry, 187, 366–371. doi: 10.1192/bjp.187.4.366.CrossRefGoogle ScholarPubMed
Li, X., Tang, Y. and de Leon, J. (2015). Clozapine for treatment-resistant bipolar disorder: a systematic review. Bipolar Disorders, 17, 235–247. doi: 10.1111/bdi.12272.CrossRefGoogle ScholarPubMed
McCarney, R. et al. (2007). The Hawthorne effect: a randomised, controlled trial. BMC Medical Research Methodology, 7, 30. doi: 10.1186/1471-2288-7-30.CrossRefGoogle ScholarPubMed
Meltzer, H. (1992). Dimensions of outcome with clozapine. British Journal of Psychiatry, 160, 46–53. doi: 10.1192/S000712500029692X CrossRefGoogle Scholar
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. and The PRISMA Group. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. British Medical Journal, 339, b2535. doi: 10.1136/bmj.b2535.CrossRefGoogle ScholarPubMed
Mukku, S. S. R., Sivakumar, P. T. and Varghese, M. (2018). Clozapine use in geriatric patients - challenges. Journal of Psychiatry, 1, 63–67. doi: 10.1016/j.ajp.2018.03.008.Google Scholar
National Institute for Health and Care Excellence (NICE). (2014). Psychosis and Schizophrenia in Adults: the NICE Guideline on Treatment and Management (NICE Guideline 178) [Online]. Available at: https://www.nice.org.uk/guidance/cg178/evidence/full-guideline-pdf-490503565; last accessed 20 July 2020.Google Scholar
Nurul Ain, M., Rosdinom, R. and Raynuha, M. (2015). Capgras syndrome in a very late onset, treatment resistant schizophrenia. International Psychogeriatrics, 27, 1573–1575. doi: 10.1017/S1041610215000332.Google Scholar
OCEBM Levels of Evidence Working Group, 2011. The Oxford 2011 Levels of Evidence [Online]. Available at: https://www.cebm.net/wp-content/uploads/2014/06/CEBM-Levels-of-Evidence-2.1.pdf; last accessed 20 July 2020.Google Scholar
Paez, A. (2017). Gray literature: an important resource in systematic review. Journal of Evidence-Based Medicine, 10, 233–240. doi: 10.1111/jebm.12266.CrossRefGoogle Scholar
Phaldessai, S., Butler, R., Radhakrishnan, R. and Basheer, M. (2019). Clozapine prescribing in older adults. International Journal of Geriatric Psychiatry, 34, 1105–1106. doi: 10.1002/gps.5114.CrossRefGoogle ScholarPubMed
Pitner, J. K., Mintzer, J. E., Pennypacker, L. C. and Jackson, C. W. (1995). Efficacy and adverse effects of clozapine in four elderly psychotic patients. Journal of Clinical Psychiatry, 56, 180–185.Google ScholarPubMed
Pridan, S., Swartz, M., Baruch, Y., Tadger, S., Plopski, I. and Barak, Y. (2015). Effectiveness and safety of clozapine in elderly patients with chronic resistant schizophrenia. International Psychogeriatrics, 27, 131–134. doi: 10.1017/S1041610214001756.CrossRefGoogle ScholarPubMed
Rostami-Hodjegan, A., Amin, A., Spencer, E., Lennard, M., Tucker, G. and Flanagan, R. (2004). 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. Journal of Clinical Psychopharmacology, 24, 70–78. doi: 10.1097/01.jcp.0000106221.36344.4d.CrossRefGoogle ScholarPubMed
Sajatovic, M., Jaskiw, G., Konicki, P. E., Jurjus, G., Kwon, K. and Ramirez, L. F. (1997). Outcome of clozapine therapy for elderly patients with refractory primary psychosis. Journal of Geriatric Psychiatry, 12, 553–558. doi: 10.1002/(SICI)1099-1166(199705)12:5%3C553::AID-GPS547%3E3.0.CO;2-U.3.0.CO;2-U>CrossRefGoogle ScholarPubMed
Sajatovic, M., Ramirez, L. F., Garver, D., Thompson, P., Ripper, G. and Lehmann, L. S. (1998). Clozapine therapy for older veterans. Psychiatric Services, 49, 340–344. doi: 10.1176/ps.49.3.340.CrossRefGoogle ScholarPubMed
Salganik, I., Modai, I., Bercovici, B. R., Kutzuk, D. and Weizman, A. (1998). Clozapine vs haloperidol therapy in elderly chronic schizophrenic inpatients - Preliminary results. A double-blind, cross-over randomized study. International Journal of Geriatric Psychopharmacology, 1, 185–187.Google Scholar
Salzman, C., Vaccaro, B., Lieff, J. and Weiner, A. (1995). Clozapine in older patients with psychosis and behavioral disruption. American Journal of Geriatric Psychiatry, 3, 26–33. doi: 10.1097/00019442-199524310-00004.CrossRefGoogle ScholarPubMed
Samara, M. et al. (2016). Efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia: a network meta-analysis. JAMA Psychiatry, 73, 199–210. doi: 10.1001/jamapsychiatry.2015.2955.CrossRefGoogle ScholarPubMed
Shulman, R. W., Singh, A. and Shulman, K. I. (1997). Treatment of elderly institutionalized bipolar patients with clozapine. Psychopharmacology Bulletin, 33, 113–118.Google ScholarPubMed
Siskind, D., McCartney, L., Goldschlager, R. and Kisely, S. (2016). Clozapine v. first- and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis. British Journal of Psychiatry, 209, 385–392. doi: 10.1192/bjp.bp.115.177261.CrossRefGoogle ScholarPubMed
Snowdon, J. and Halliday, G. (2011). A study of the use of clozapine in old age psychiatry. International Clinical Psychopharmacology, 26, 232–235. doi: 10.1097/YIC.0b013e32834405fc.CrossRefGoogle ScholarPubMed
Vasile, J. S. and Steingard, S. (1995). Clozapine and the development of salivary gland swelling: a case study. Journal of Clinical Psychiatry, 56, 511–513.Google ScholarPubMed
Vermeulen, J. M., van Rooijen, G., van de Kerkhof, M. P. J., Sutterland, A. L., Correll, C. U. and de Haan, L. (2019). Clozapine and long-term mortality risk in patients with schizophrenia: a systematic review and meta-analysis of studies lasting 1.1–12.5 years. Schizophrenia Bulletin, 45, 315–329. doi: 10.1093/schbul/sby052.CrossRefGoogle ScholarPubMed