03. Insomnia in the Elderly: Do Sedatives Increase or Decrease Fall Risk?

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Insomnia in Older Patients: Challenging Conventional Wisdom

Imagine you have an older patient who complains of insomnia which is significantly impacting their quality of life. Perhaps, they experience initial insomnia with difficulty falling asleep due to ruminative thoughts or maybe they have terminal insomnia, common in older adults as the pineal gland begins to secrete less melatonin as we age and your patient awakens every morning at 3:30 unable to fall back to sleep or maybe you have an older male patient whose enlarged prostate has led to frequent nighttime awakenings to urinate with difficulty falling back to sleep afterwards.

Benzos and Z-Drugs: Are They Really Bad for Older Adults?

Conventional teaching would hold that you should be very cautious about prescribing a benzodiazepine or a Z-drug like zolpidem for these patients because of the risk for falls. Most of us were taught that benzos are bad in older adults. A new study may challenge that teaching and provide an alternate explanation for the increased risk of falls and fractures in patients taking these medications.

Danish Study Reveals Surprising Findings

In this study published in ACTA Psychiatrica Scandinavica, the authors examined nearly 700,000 adult patients in the Danish national prescription and patient registries. About 62,000 adults experienced a fall during the 14-year study period and about 38,000 experienced a fracture. The seven most commonly prescribed agents were alprazolam, chlordiazepoxide, diazepam, oxazepam, zolpidem, zopiclone and melatonin with Z-drugs being the most commonly prescribed class.

Insomnia Itself May Drive Increased Risk for Falls

The study’s most important finding was that the risk for falls was actually highest in the immediate pretreatment period, that is three months before starting the medication and decreased steadily from there but remained elevated above baseline in all phases of the treatment period. Based on this, the authors conclude that the association of sedative drugs with falls and fractures is likely reflective of the indication for the medication increasing the risks of those outcomes. More specifically, insomnia itself or associated factors like anxiety might actually drive the increased risk for falls and their sequelae. And medications prescribed for insomnia like sedative hypnotics might actually decrease the risk.

Surprising Results for Alprazolam and Melatonin

In sub-analyses, a few other things stand out:

• Alprazolam was the only medication examined individually that was not associated with a higher risk for fractures at all.
• When melatonin was looked at individually, the results were the same, challenging the belief that it is a safer alternative.

Interpreting the Findings: A Need for Individualized Risk-Benefit Analysis

One way to interpret the findings would be to consider that perhaps sedatives don’t really prevent falls but that their benefit in improving insomnia outweighs any increased risk they may confer and thus improves overall outcomes. Or maybe it’s possible that what we’ve been taught all along is actually wrong and that sedatives don’t directly cause falls. Maybe insomnia actually represents a much more important risk factor for falls.

As a prescriber, this is another good example of the need to conduct an individualized risk-benefit analysis for every patient. Being dogmatic is often easier for the prescriber but less helpful for patients.

CBT for Insomnia: The First-Line Recommendation

That’s why CBT for insomnia is now considered the first-line recommendation. Most sleep specialists would say that treatment for every patient should begin with CBT though many patients will cite practical barriers or have difficulty complying with sleep hygiene.

For patients who do ultimately need pharmacotherapy for insomnia, having a wide armamentarium may serve you better than narrowly prescribing only a few agents or a single class especially when studies like this challenge principles we think we know about psychopharmacology.

Abstract

Use of hypnotic-sedative medication and risk of falls and fractures in adults: A self-controlled case series study

Maarten Pieter Rozing, Marie Kim Wium-Andersen, Ida Kim Wium-Andersen, Terese Sara Høj Jørgensen, Martin Balslev Jørgensen, Merete Osler. John Wiley & Sons Ltd

OBJECTIVE

To evaluate the risk of falls and fractures in users of benzodiazepines, Z-drugs, or melatonin.

METHODS

We followed 699,335 adults with a purchase of benzodiazepines, Z-drugs, or melatonin in the Danish National Prescription Registry between 2003 and 2016 for falls and fractures in the Danish National Patient Registry between 2000 and 2018. A self-controlled case-series analysis and conditional Poisson regression were used to derive incidence rate ratios (IRR) of falls and fractures during six predefined periods.

RESULTS

In total 62,105 and 36,808 adults, respectively, experienced a fall or fracture. For older adults, the risk of falls was highest during the 3-month pre-treatment period (IRRmen+70, 4.22 (95% confidence interval, 3.53–5.05), IRRwomen + 70, 3.03 (2.59–3.55)) compared to the baseline (>1 year before initiation). The risk continued to be higher in the later treatment periods. Contrarily, in men and women aged 40–69 years, the risk was only higher in the 3-month pre-treatment period. The incidence of falls among young men and women was slightly lower after initiation of sedating medication (treatment period, IRRmen15–39, 0.66 (0.50–0.86), IRRwomen15–39, 0.65 (0.51–0.83)). Analyses with fractures as outcome yielded similar results.

CONCLUSIONES

Although falls and fractures occur more often in persons using sedative-hypnotic medication, the higher risk of falls and fractures in the pre-treatment period relative to the period directly after treatment, suggests that this association is better explained by other factors that elicited the prescription of this medication rather than the adverse effects of the sedativehypnotic medication.

Reference

Rozing, M., Wium-Andersen, M., Wium-Andersen, I., Jørgensen, T., Jørgensen, M., Osler, M. (2023). Use of hypnotic-sedative medication and risk of falls and fractures in adults: A self-controlled case series study. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.