[e-drug] Insomnia treatments harmful and not effective

["E-Drug" <e-drug@healthnet.org>]

E-DRUG: Insomnia treatments harmful and not effective
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[this is of course old news to many e-druggers, but why do keep GPs prescribing benzodiazepines for insomnia? Is it lack of time, too much promotion by industry or assertive patients?
And how can we get rid of these prescriptions and dependencies?
WB]

http://bmj.bmjjournals.com/cgi/content/full/329/7476/1198 

BMJ  2004;329:1198-1199 (20 November), doi:10.1136/bmj.329.7476.1198 

Treating insomnia 

Use of drugs is rising despite evidence of harm and little meaningful
benefit 

"By the way, doctor, I don't sleep at night. Can you give me something
for that?" or "You can take away any of my other pills, but I have to
have something for sleep!" are sentiments heard daily in any general
medical environment. Patients with persistent complaints of insomnia -
often elderly, frail, with multiple morbidities, multiple medications,
already on or previously on a hypnotic medication - become problematic.
Once past invoking sleep hygiene guidelines; looking for primary causes
of insomnia; discussing medication risks such as falls, impaired
cognition, driving crashes, and dependence; or discontinuing sedatives
(and grumbling to the nurses for promoting them and to the house staff
and referring doctors for prescribing them), what is the doctor to do?
Why is this one of the least satisfying symptoms to treat and to educate
medical professionals about? 

Perhaps because the definition of "normal sleep" remains elusive, as do
the determinants of normal sleep, the correlation of psychopathology
(which many doctors have neither time nor training to deal with
appropriately) with poor sleep satisfaction is strong, the independent
prognostic importance of insomnia itself is unknown, and the well known
drug treatments for insomnia all have uncertain but worrisome ratios of
harm to benefit.1 2 Once the time consuming sedative prevention or
withdrawal exercise is completed, one has a sense of resigned
acknowledgment that most patients persist with their complaint until
some doctor finally prescribes and represcribes a sedative. 

Despite evidence of major harm and little evidence of clinically
meaningful benefit, prescriptions for benzodiazepines continue to grow
and are part of a "top 20" list of prescribed drugs in many
jurisdictions.3 Furthermore, although their use is associated with poor
functional status, cognitive impairment, daytime sleepiness, falls, and
depressed mood, patients' satisfaction with effectiveness is high.4-6 

The conclusions of the recent guidance from the National Institute for
Clinical Excellence (NICE) on newer hypnotic drugs will be a
disappointment to those clinicians who were holding out hope that the
newer "Z" drugs (zaleplon, zolpidem, and zopiclone) are superior to
benzodiazepines in effectiveness or safety.7 The guidance, while limited
to comparisons between the Z drugs and benzodiazepines, is the usual,
high quality NICE product, with a comprehensive systematic review
including industry submissions, extensive stakeholder consultation, and
a highly readable summary of findings. 

Although initially promoted as superior to benzodiazepines in terms of
daytime sedation, dependence, and withdrawal, the Z drugs have not
delivered on several fronts. On the quality of evidence, of the 17
randomised trials with a total of 1284 patients, all were industry
funded, outcomes were poorly and often selectively reported in favour of
positive findings, comparators were suboptimal, durations were very
short (maximum six weeks), and surrogate markers (generally sleep
variables) were highlighted.7 On the risk-benefit front, no consistent
difference was found between the Z drugs and benzodiazepines for either
effectiveness or safety.7 On the economic front, since the Z drugs are
each several times the cost of older benzodiazepines, without evidence
of superior effectiveness, they cannot be considered cost effective. 

With the NICE guidance added to the weighty pile of negative evidence
and expert opinion on hypnotic agents, do reasonable alternatives exist?
Drugs are still important considerations in two main areas. Firstly,
some commonly used drugs are well known to disrupt normal sleep -
notably alcohol, selective serotonin reuptake inhibitors, drugs for
Parkinson's disease, methyxanthines, and diuretics - and should be
considered as potential contributors to the insomnia. Secondly, drugs
can be effective for causes of secondary insomnia, especially pain and
depression. Antidepressant medications are increasingly being prescribed
for insomnia8; whether they are safe and effective outside of
depression-associated insomnia is still controversial. The use of
antidepressants, antipsychotics, or anticholinesterase inhibitors for
insomnia related to delirium or dementia is also unproved. 

No drug has yet been shown to be more effective and safer than placebo
in primary insomnia for the type of outcomes that matter, such as
quality of life, daytime function, cognition, falls and fractures, or
dependency. Placebo itself, as in every domain of therapeutics, has been
found to be effective - in this case in improving sleep.9 The current
aim of treatment is less focused on reduction of arousal from sleep and
more focused on changing beliefs and attitudes about sleep.10 Thus
NICE's recommendation that long term, non-pharmacological interventions
for insomnia should be a primary target for evaluation of cost
effectiveness. Although physical exercise shows merit and can be
recommended by primary care providers,11 the current front runner for
non-pharmacological treatment is cognitive behaviour therapy,12 w1 w2 w3
a technique not familiar to providers outside of psychiatry. Trials of
different methods of training family doctors in cognitive behaviour
therapy are currently under way. 

Cognitive behaviour therapy has many elements - stimulus control (your
bed is only for sleep), sleep restriction (restrict your time in bed to
your usual sleeping time), sleep hygiene, and relaxation therapy. Which
of these elements are effective is unclear, but this is worth finding
out as more passive interventions, such as audit and feedback to primary
care doctors, are not effective.w4 In the meantime, the newer hypnotics
remain with the older hypnotics as prime examples of iatrogenesis
imperfecta. 

Anne M Holbrook, director 

Division of Clinical Pharmacology, McMaster University, Hamilton, ON,
Canada L8N 3Z5 (holbrook@mcmaster.ca) 
--------------------------------------------------------------------------------

Additional references w1-w4 are on bmj.com 
Competing interests: None declared. 

References
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et al. Insomnia and the eye of the beholder: are there clinical markers
of objective sleep disturbances among adults with and without insomnia
complaints? J Consult Clin Psychol 2000;68: 586-93.
2. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of
benzodiazepine use in the treatment of insomnia. CMAJ 2000;162: 225-33.
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