Benzodiazepines and Z drugs may increase the risk of death and cancer, according to new cohort study


The prescribing of benzodiazepines and ‘Z drugs’ in general practice in England has stayed pretty consistent or increased slightly over the last 5 years, despite safety warnings about the risks of these drugs.

I blogged about this back in May last year when the Department of Health highlighted two new studies by National Addiction Centre and National Treatment Agency for Substance Misuse, which expressed concerns about the potential addiction to these medicines.

A large US observational study has now been published that shows an increased risk of death and cancer is associated with use of hypnotics, even in relatively small doses.

The study used a one-to-two matched cohort design; using a large database to identify patients who were prescribed hynoptics for insomnia and survived for 3 months or longer. Over 10,000 patients who received hynoptics were followed up for 2.5 years and matched with over 20,000 people who had no hynoptics.

The study looked at 8 commonly used hypnotics:

  1. Zolpidem
  2. Temazepam
  3. Eszopiclone
  4. Zaleplon
  5. Triazolam
  6. Flurazepam
  7. Barbiturates
  8. Sedative antihistamines

Records were examined to see how many people subsequently died or were diagnosed with a major cancer. Data were adjusted for age, gender, smoking, body mass index, ethnicity, marital status, alcohol use and prior cancer. Multiple strategies were used to address confounding by health status.

Here’s what they found:

  • People who were prescribed hypnotics had significantly elevated hazards of dying compared to those prescribed no hypnotics
  • A dose-response relationship was seen. Hypnotics were also associated with a significantly increased risk of cancer, except in patients taking fewer than 18 doses/year
  • Over a mean follow-up of 2.5 years, 6.1% of hypnotic users died, compared with 1.2% of non-users
  • Hazard ratios were:
    • 3.60 (95% confidence interval [CI] 2.92 to 4.44) for 0.4 to 18 doses/year
    • 4.43 (95% CI 3.67 to 5.36) for 18 to 132 doses/year
    • 5.32 (95% CI 4.50 to 6.30) for more than 132 doses/year

This kind of observational study design cannot prove that hypnotics increase the risk of death and cancer, but the dose-response relationship that is seen is another reason to exercise caution when considering prescribing hypnotics.

Prescribers should once again take note that benzodiazepine hypnotics should be used only if insomnia is severe, disabling or causing the patient extreme distress. The lowest dose possible should be used to control symptoms, for a maximum of 4 weeks and intermittently if possible.

NICE recommends that non-drug treatments should be considered before hypnotics are prescribed, e.g. advice on good sleep practices, avoiding stimulants, maintaining regular sleeping hours with a suitable environment for sleep and cognitive behavioural therapy.


Kripke DF, et al. Hypnotics’ association with mortality or cancer: a matched cohort study. BMJ Open 2012;2:e000850 doi:10.1136/bmjopen-2012-000850

Insomnia – newer hypnotic drugs (TA77). NICE, April 2004.

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Andre Tomlin

André Tomlin is an Information Scientist with 20 years experience working in evidence-based healthcare. He's worked in the NHS, for Oxford University and since 2002 as Managing Director of Minervation Ltd, a consultancy company who do clever digital stuff for charities, universities and the public sector. Most recently André has been the driving force behind the Mental Elf and the National Elf Service; an innovative digital platform that helps professionals keep up to date with simple, clear and engaging summaries of evidence-based research. André is a Trustee at the Centre for Mental Health and an Honorary Research Fellow at University College London Division of Psychiatry. He lives in Bristol, surrounded by dogs, elflings and lots of woodland!

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