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This questionnaire study of patients’ with insomnia reported no advantage for the Z drugs over benzodiazepines either in helping them sleep or in causing fewer adverse effects. Prescribing practices were often contrary to both the NICE guidance and the product licence.
Action
Prescribers should be familiar with the NICE guideline on insomnia which advises that after non-drug therapies have been explored, hypnotics should be used in the lowest dose possible for no more than 4 weeks in the case of benzodiazepines and between 2 and 4 weeks with Z drugs. This study suggests that this guidance is not being followed in the UK. It also brings some ‘real world’ support to the clinical trial evidence that there is no perceptible advantage for the ‘Z drugs over benzodiazepines in either efficacy, adverse effects or in causing dependency in Z drugs compared to benzodiazepines.
What is the background to this?
We know from a large systematic review that, compared with placebo, benzodiazepines do not reduce time to fall asleep, but may increase sleep duration by an hour at the expense of increased adverse effects. NICE considered the evidence from 24 randomised controlled trials [RCTs] comparing Z drugs (such as zopiclone, zolpidem, or zaleplon) to benzodiazepines or to each other in patients with insomnia. NICE also reviewed 9 RCTs in which insomnia had been induced in healthy participants. They concluded that both the evidence from studies involving people with insomnia and those using healthy volunteers showed no consistent difference between Z drugs and benzodiazepines. There was little consistency in reporting of adverse events which prevented comparison of individual event rates or meta analysis. Furthermore, data submitted regarding tolerance and dependency associated with Z drugs were not considered methodologically sound and no comparisons had been made between Z drugs and benzodiazepines currently prescribed on the NHS.
What does this study claim?
A questionnaire was sent out to 1600 general practice patients in Lincolnshire who had received at least one prescription for a Z drug or benzodiazepine in the previous 6 months. 705 of those who replied were taking hypnotics for insomnia. Almost all had been taking their hypnotic for longer than 4 weeks with the vast majority taking hypnotics for over a year ((14.3% for 4-52 weeks); 80.6% for over 1 year) There was no significant difference in benefits (odds ratio (OR) 1.45, 95% Confidence Interval (CI) 0.74 to 2.84) or adverse effects (OR 0.74, 95% CI 0.49 to 1.13), including withdrawal symptoms (OR 0.79, 95% CI 0.54 to 1.16) or dependence (OR 1.31, 95% CI 0.94 to 1.8) between Z drugs and benzodiazepines. Repeat prescriptions accounted for 92.1% of all hypnotic prescriptions, with 67.4% taking daily medication. Many responders (42.3%) had not been advised regarding duration of treatment and of those who had received guidance 45.4% were advised to continue treatment longer than licensed recommendations. However, 87% felt their insomnia had improved on medication, 72.1% wanting to continue treatment.
How does this relate to other studies?
Prescribing data in England* show that many prescriptions for benzodiazepine and Z drugs are for quantities beyond the recommended duration of treatment. These data also indicate an increasing trend towards prescribing Z drugs in comparison to benzodiazepines despite the lack of evidence supporting greater efficacy of Z drugs over benzodiazepines. NICE guidelines state that Z drugs and benzodiazepines are comparable in terms of side-effects and dependence despite a general perception favouring Z drugs on these terms.
So what?
In the discussion section of this study the research and clinical implications are discussed. This study supports the lack of increased efficacy of Z drugs and similar adverse event rates compared to benzodiazepines. The discussion suggests the possibility of higher rates of dependence with Z drugs versus benzodiazepines. However, while more people reported dependence on Z drugs (57.8% vs 53.7%), the difference was not statistically significant (dependent/ at risk of becoming dependent OR 1.31, 95% CI 0.94 to 1.8). Prescribers and patients need to be aware of the lack of difference in adverse effects between these two types of drug. The indication for short term use only should be emphasised. The results indicate use of and further research into non-pharmacological management of insomnia should be encouraged.
NICE guidance should be followed but this will require a significant change in current practice by patients, prescribers and health care organisations.
Study details
Design: A cross-sectional survey of 1600 general practice patients from 32 practices in Lincolnshire, UK of which 935 (58.4 %) had received at least one prescription for a Z drug or benzodiazepine in the previous 6 months. Of the responders 705 (75.4%) were taking the drugs for insomnia. Analysis excluded anyone taking drugs for reasons other than insomnia.
Patients: Responders were aged between 18 and 85+ years that had been prescribed benzodiazepines or Z drugs in the previous 6 months.
Intervention and comparison: Patients’ use and experiences of newer (Z drugs) versus older (benzodiazepine) hypnotics for insomnia in primary care.
Outcomes: Comparison of patients use and experience of Z drugs to benzodiazepines specifically benefit, adverse effect, dependency and withdrawal.
Results: Of the 705 responders taking drugs for insomnia 87.9% (n=620) were first prescribed a sleeping tablet by their GP and 94.9% (n=669) had taken a hypnotic for 4 weeks or more. Z drugs were prescribed more commonly (370 of 705; 52.5%) than benzodiazepines (268 of 705; 38%). There was no significant difference between Z drugs and benzodiazepines in apparent benefits (OR 1.45, 95% CI 0.74 to 2.84) or adverse effects (OR 0.74, 95% CI 0.49 to 1.13), including withdrawal (OR 0.79, 95% CI 0.54 to 1.16) or dependence (OR 1.31, 95% CI 0.94 to 1.8).The majority of responders (87%, n=613) reported an improvement in their insomnia and 72.1% (n=508) wished to remain on medication.
Sponsorship: Trent Research and Development Support Unit and the Health Foundation.
Feedback
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The primary author of this blog is Elisabeth Maskrey, 3rd year medical student at Hull York Medical School.
* Personal Communication. NHS Business Service Authority Prescription Pricing Division (NHSBSA PPD) 2008