Clozapine use in old-age psychiatry-indications, dose range, rate of titration and side effects during titration

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Raghavakurup Radhakrishnan, Phaldesai S, Butler R and Basheer M

Nothshore hospital Auckland, New Zealand

: Androl Gynecol: Curr Res

Abstract

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Background: Clozapine is routinely prescribed to older adults in mental health services but there is very limited published data about the indications, titration rates or dosages. In the elderly, clozapine has been mainly used in treatment resistant schizophrenia treatment resistant bipolar disorder psychosis in elderly patients with Parkinson’s disease and for treatment resistant agitation in dementia.

Aim: This study aimed at quantifying the indications, titration rates and dosages of clozapine and comparing them to clinical guidelines. In the second step of the study, the survey responses from consultant psychiatrists were analysed to assess attitudes with regards to clozapine use in the elderly.

Methods: We looked at the electronic records of all adults aged 65 or over prescribed clozapine in a mental health service over a 10 year period. Clozapine titration rate in older adults was compared with a standard titration protocol published by Bleakley and Taylor in 2013.

Results: There were two major indications for clozapine: Dementia with Lewy bodies and treatment resistant schizophrenia. Titration rates were significantly slower than guidelines. The peak doses were 32mg and 104 mg for the two groups respectively. The recommended doses are 50mg and 250mg. This may be accounted for by the large range of co-morbidities and adverse-effects. Ninety five percent of people who completed titration (n=35/37) made a good recovery. In terms of side effects patients experienced an average of 2.0 side effects related to clozapine (mean 2.23, SD+/-). These included constipation, 60.0%; sialorrhea, 17.5%; falls, 17.5%; dizziness, 12.5%; unsteadiness, 20.0%; sedation, 37.5%; postural hypotension, 30.0%; extra-pyramidal side effects, tiredness, nocturnal urinary incontinence, and pneumonia, each 5.0%; and dry mouth, excessive sweating, myocarditis, and pericarditis, each 2.5%.

Conclusions: This study suggests older people are prescribed clozapine at a much slower titration rate and lower dose than recommended guidelines. However, outcomes were very good suggesting that clozapine has a wider role to play in treating mental illness in older adults.

Recent Publications:

1. 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(1):131-4.

2. Bishara D and Taylor D (2014) Adverse effects of clozapine in older patients: Epidemiology, prevention and management. Drugs & aging 31(1):11-20.

3. Lee H B, Hanner J A, Yokley J L, Appleby B, Hurowitz L and Lyketsos C G (2007) Clozapine for treatmentresistant agitation in dementia. Journal of geriatric psychiatry and neurology 20(3):178-82.

4. Klein C, Gordon J, Pollak L and Rabey J M (2003) Clozapine in Parkinson’s disease psychosis: 5-year follow-up review. Clinical neuropharmacology 26(1):8-11.

5. Bleakley S and Tylor D (2013) The Clozapine Handbook. Lloyd-Reinhold Communications LLP.

Biography

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Raghavakurup Radhakrishnan works as a Consultant Psycho-Geriatrician at Waitemata District Health Board, Nothshore Hospital Auckland and an Honorary Lecturer in Psychiatry with University of Auckland. His research interests are mainly in dementia and delirium. He has published his research in various journals on delirium and dementia, contributed a chapter on dementia in BMJ clinical evidence and currently contributing chapter on fronto-temporal dementia in BMJ best practice. His interests include research methodology and statistics. His qualifications include MBBS, DPM (NIMHANS), Diplomate of National Board of Examinations in Psychiatry (India); MRCPsych (Royal college of Psychiatry, United Kingdom). H has completed CCT in Old Age Psychiatry with Eastern Deanery, United Kingdom. He worked as a Consultant in Cambridge and Peterborough NHS trust and later with Rotherham, Doncaster and South Humber NHS trust before moving to New Zealand.