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The Association of Benzodiazepines and z-drugs with Mortality in Patients with Cancer: a Systematic Review.

Background: Benzodiazepines and Z-drugs are commonly used in patients with cancer for the management of symptoms such as anxiety, agitation and dyspnoea. Clinical staff, patients and relatives have concerns about the impact of these drugs on survival. This potentially decreases prescribing leading to suboptimal symptom control. The aim of this systematic review was to find and assimilate the evidence assessing the association of benzodiazepines and Z-drugs with survival in patients with cancer, to assist in clinical decision-making regarding the use of these drugs in cancer patients.

Methods: Systematic review with narrative synthesis designed and conducted according to the recommendations set out in Preferred Reporting Items for Systematic Reviews and MetaAnalyses-Protocol (PRISMA-P) and PRISMA statements. The review protocol was registered on the PROSPERO prior to commencing the searches. The electronic databases MEDLINE, EMBASE, PsychINFO, Cochrane Library, AMED were searched and hand-searches were performed. Screening, extraction and quality assessment were performed in duplicate.

Results: A total of 2257 unique records were identified, 116 full-text articles assessed for eligibility, 18 met the inclusion criteria. These contained data on 4117 patients with cancer. All studies were low or very-low quality. Most studies were conducted in patients in the last days/weeks of life. No study found an association between benzodiazepines and survival in patients with cancer.

Conclusions: There is no evidence demonstrating an association between benzodiazepines and survival in patients with cancer. These results should be interpreted with caution as all studies were low/very low quality, most did not report or account for other medications and did not have survival as a primary outcome. No study assessed the effect of long-term benzodiazepines on survival. Therefore, definitive conclusions regarding survival impact of benzodiazepine in patients with cancer can be made. Further investigation using high-quality long-term randomised control trials with survival as a primary endpoint are needed.

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