Buhagiar, Kurt, Templeton, Georgia, Blyth, Henrietta, Dey, Mrinalini and Giacco, Domenico (2020) Mortality risk from long-term treatment with antipsychotic polypharmacy vs monotherapy among adults with serious mental illness : a systematic review and meta-analysis of observational studies. Schizophrenia Research . doi:10.1016/j.schres.2020.08.026 (In Press)

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Abstract

Background:
Long-term use of more than one concurrent antipsychotic [antipsychotic polypharmacy (APP)] is widely believed to contribute to excess mortality in people with serious mental illness (SMI) compared to those taking only one antipsychotic (monotherapy). However, no conclusive evidence is available.

Methods:
We conducted a systematic search in 6 major electronic databases from inception until December 2019, identifying observational studies examining the association between mortality and exposure to long-term APP vs monotherapy. Studies were eligible if they adopted a follow-up design and antipsychotic exposure was >3 months among adults with SMI. We determined the pooled mortality risk using random-effects meta-analyses. The review was registered in PROSPERO (CRD42019148044).

Results:
A total of 12 studies fulfilled all eligibility criteria reporting quantitative data for 834, 534 person years. No difference was found in the association between all-cause mortality and APP vs monotherapy use, in both crude (rate ratio = 0.94, 95% CI 0.81–1.10, p = 0.446; I2 = 83.2%, p < 0.001; 10 studies) and adjusted models (adjusted HR = 0.98, 95% CI 0.80–1.19, p = 0.802; I2 = 58.3%, p < 0.05; 5 studies). Meta-regression did not identify any moderators influencing all-cause mortality risk. For natural causes of death, risk estimates followed the same pattern: (i) crude rate ratio = 0.88, 95% CI 0.67–1.14, p = 0.324; I2 = 77.7%, p = 0.01 (5 studies); (ii) adjusted HR = 1.04, 95% CI 0.90–1.99, p = 0.590; I2 = 0.0%, p = 0.744 (5 studies).

Conclusion:
Mortality risk of APP use in people with SMI appears to be comparable to that of monotherapy use, although work to date remains heterogeneous, precluding firm conclusions from made. Complex real-world clinical scenarios may be contributing to this lack of variation between these two types of antipsychotic use.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history Q Science > QP Physiology R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School > Health Sciences > Mental Health and Wellbeing Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Mortality, Death (Biology) , Antipsychotic drugs, Antipsychotic drugs -- Side effects , Polypharmacy, Schizophrenia , Schizophrenia -- Diagnosis
Journal or Publication Title:	Schizophrenia Research
Publisher:	Elsevier BV
ISSN:	0920-9964
Official Date:	15 September 2020
Dates:	Date Event 15 September 2020 Available 29 August 2020 Accepted
Date of first compliant deposit:	20 November 2020
DOI:	10.1016/j.schres.2020.08.026
Status:	Peer Reviewed
Publication Status:	In Press
Access rights to Published version:	Restricted or Subscription Access

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