From the Editor

With his depressive episode, he can’t sleep. While he thinks cannabis may be worsening his anxiety, in his view, a couple of joints before bed is the only thing that seems to help with the insomnia.

My patient’s problems are common. So many of our patients struggle with insomnia. How should we assess it? What’s evidence-based care? And what can we suggest to replace that cannabis? This week, we open with the new review from The New England Journal of Medicine. Charles M. Morin (of Université Laval) and Dr. Daniel J. Buysse (of the University of Pittsburgh) provide timely advice in their paper. They consider scales that could be incorporated into practice, evidence for CBT-I, and different medications. “Recommended therapies for insomnia produce clinically meaningful reductions in insomnia symptoms, sleep-onset latency, and time awake after sleep onset.” We summarize the paper and weigh its implications.

Counting sheep may not always work

With growing evidence for CBT-I, digital options are increasingly appealing due to their convenience and accessibility. In the second selection, Jake Linardon (of Deakin University) and his co-authors report on a study looking at the effectiveness of app-based interventions for insomnia, just published in Sleep Medicine. In this meta-analysis, they drew on 19 RCTs including different treatments like CBT. “Findings suggest that stand-alone app-based interventions can effectively address insomnia and sleep disturbances, and may play an important role in the management of these symptoms.”

And in the third selection, Dr. Joanna Cannon, a UK physician and bestselling author, discusses her insomnia in an essay for The Guardian. She describes the impact on her life and her unusual way of coping. She also notes the origin of the problem: “It was when I started training as a doctor that my atypical sleeping habits became embedded.”

DG

Selection 1: “Management of Insomnia”

Charles M. Morin and Daniel J. Buysse

The New England Journal of Medicine, 18 July 2024

Insomnia disorder is characterized by dissatisfaction with sleep quality or duration associated with difficulty falling or staying asleep and substantial distress or daytime impairments. The disorder is a sleep disturbance that occurs 3 nights or more per week, persists for more than 3 months, and is not the result of inadequate opportunities for sleep. It frequently co-occurs with other medical conditions (e.g., pain) and psychiatric disorders (e.g., depression), as well as other sleep disorders (e.g., restless legs syndrome and sleep apnea).

So begins a paper by Morin and Buysse.

On insomnia

“Insomnia is the most prevalent sleep disorder in the general population and among the most frequent issues raised by patients during primary care visits, although it often goes untreated. Approximately 10% of adults meet the criteria for insomnia disorder and another 15 to 20% report occasional insomnia symptoms. Insomnia is more prevalent among women and persons with mental or medical problems, and its incidence increases in middle age and later, as well as during perimenopause and menopause…”

The assessment

“The assessment and diagnosis of insomnia rests on a careful history to document symptoms, course, co-occurring conditions, and other contributing factors. A 24-hour history of sleep–wake behaviors may identify additional behavioral and environmental targets for intervention. Patient-reported assessment tools and sleep diaries can provide valuable information about the nature and severity of insomnia symptoms, help screen for other sleep disorders, and monitor treatment progress.”

CBT-I

“CBT-I is currently the first-line treatment recommended in the practice guidelines of several professional organizations…

“CBT-I involves a combination of strategies aimed at changing the behavioral practices and psychological factors (e.g., excessive worries and unhelpful beliefs about sleep) that contribute to insomnia. The core components of CBT-I include behavioral and sleep-scheduling strategies (sleep restriction and stimulus control instructions), relaxation methods, psychological and cognitive interventions (or both) aimed at changing unhelpful beliefs and excessive worrying about insomnia, and sleep hygiene education…

“In meta-analyses of these trials, CBT-I showed improvement in insomnia-symptom severity (effect size, 0.98…), sleep-onset latency (effect size, 0.57…), and time awake after sleep onset (effect size, 0.63…).” They also note improvement in sleep time (effect size, 0.16…) but with the biggest effect sizes are strongest for global insomnia symptom severity.

They note digital options. “Digital CBT-I (eCBT-I) has gained in popularity over the past decade and could eventually narrow the important gap between demand and access to CBT-I.”

Medications

“Prescribing patterns for hypnotic medications in the United States have changed substantially over the past 20 years. Prescriptions for benzodiazepine receptor agonists have steadily decreased and prescriptions for trazodone have steadily increased.”

They focus on several classes. Here, we mention a few.

Benzodiazepines. “Benzodiazepine receptor agonist hypnotics include benzodiazepines and nonbenzodiazepines (also known as Z-drugs). These subclasses have different chemical structures, but both are allosteric modulators of a common binding site on γ-aminobutyric acid type A (GABA A) receptors, which accounts for their similar actions and side effects. Clinical trials and meta-analyses have shown the efficacy of benzodiazepine receptor agonists for reducing sleep-onset latency and wakefulness after sleep onset, with small increases in total sleep time. Patient-reported side effects of benzodiazepine receptor agonists include anterograde amnesia (in <5%), next-day sedation (in 5 to 10%), and complex behaviors during sleep, such as sleepwalking, eating, or driving (in 3 to 5%), a side effect that is responsible for black-box warnings for zolpidem, zaleplon, and eszopiclone…” They note the problems of “drug tolerance and physiological dependence marked by rebound insomnia and withdrawal syndromes” occurring in 20 to 50% of patients with repeated nightly use. “Substance use disorder involving benzodiazepine receptor agonists is uncommon” – though they note misuse is common.

Sedating antidepressants. “Sedating antidepressant drugs, including tricyclic drugs (e.g., amitriptyline, nortriptyline, and doxepin) and heterocyclic drugs (e.g., mirtazapine and trazodone), are commonly prescribed to treat insomnia. Of these, only doxepin (at a dose of 3 to 6 mg daily, taken at night) is FDA-approved for insomnia. The lower doses used in insomnia than in depression and the more rapid onset of action in insomnia than in depression suggest distinct mechanisms of action for these indications. Despite their widespread use, the efficacy of the sedating antidepressants in the treatment of insomnia is not well supported by controlled trials, except in the case of doxepin.”

Melatonin. “Melatonin is a pineal hormone that is endogenously secreted during darkness at night. Exogenous melatonin produces supraphysiologic blood levels for varying durations depending on the specific dose and formulation. The appropriate dose of melatonin for treating insomnia is not defined. Controlled trials involving adults have shown a small effect on sleep onset, with little effect on wakefulness during sleep or on total sleep time.”

A few thoughts:

1. This is an excellent review paper. It’s a must read for clinicians.

2. There is much to like here.

3. How to approach care in a thoughtful way? They offer the following: “Stepped-care approaches may help to address resource limitations with traditional psychological and behavioral therapies. One such model recommends education, monitoring, and self-help approaches at the first level, digital or group-based psychological and behavioral treatment at the second level, individual psychological and behavioral treatment at the third level, and pharmacotherapy as a short-term adjunct at each level.” Excellent.

4. They make good and important points about digital tools. What is the latest evidence for apps? The next selection offers insight.

The full NEJM review can be found here:

https://www.nejm.org/doi/abs/10.1056/NEJMcp2305655

Selection 2: “The effectiveness of smartphone app-based interventions for insomnia and sleep disturbances: A meta-analysis of randomized controlled trials”

Jake Linardon, Cleo Anderson, Zoe McClure, et al.

Sleep Medicine, October 2024

Insomnia is a chronic and debilitating condition affecting between 10 and 15% of the global population. It has a high burden of disease and negatively impacts the quality of life and day-to-day functioning of the individual… There are many options available for the treatment of insomnia… [P]sychological and behavioral approaches such as cognitive-behavioral therapy (CBT) and, to a lesser extent, mindfulness-based interventions have accrued empirical support for their ability to effectively and safely treat insomnia and sleep disturbances in both the short and longer-term…

One form of technology that can be used to administer psychological treatment principles at scale is smartphones. Smartphones are among the most rapidly adopted technological innovations in recent history, with over 6.5 billion people owning a smartphone and keeping it within arm’s reach at almost all times. Applications (apps) that host intervention programs can be accessed anytime, anywhere and without the need for professional support. Apps are also capable of doing things that are not possible in conventional treatment, such as delivering personalized interventions in real-time based on the passive and active data continuously collected… There are dozens of publicly available apps for insomnia in the marketplace, yet prior reports expressed concern about the lack of scientific evidence supporting their efficacy.

So begins a paper by Linardon et al.

Here’s what they did:

  • They conducted a meta-analysis investigating the effectiveness of apps for insomnia and sleep disturbances. 
  • They included RCTs that “tested the effects of a mental health or behavioral intervention delivered via a smartphone app against a control group in samples pre-selected, either via clinical interview or self-report, for insomnia or sleep-related difficulties.”
  • They calculated pooled effect sizes for the primary outcomes of self-reported insomnia and sleep disturbances.
  • They also assessed bias using the Cochrane Collaboration Risk of Bias tool.

Here’s what they found:

  • They assessed more than 1 700 records; after excluding duplicates and doing some basic screening, 138 papers were reviewed with 19 meeting inclusion criteria.
  • Characteristics. “Fifteen studies pre-selected participants on the basis of self-reported, while four used clinical interviews.” In terms of the intervention, most apps were based on CBT principles (15); mindfulness (2) and lifestyle modifications (3) were also used.
  • Pooled effect sizes. “From 19 RCTs, we identified significant pooled effect sizes for the primary outcomes of self-reported insomnia (g = 0.60…; NNT = 4.8) and sleep disturbances (g = 0.70…; NNT = 4.1) in favour of apps over control conditions.”
  • Analyses. “These effects remained robust when restricting the analyses to trials that delivered a placebo control, received a lower risk of bias rating, and had a larger sample size.” 
  • Secondary outcomes. “Significant pooled effects in favour of apps were also observed for secondary outcomes of night time awakenings (g = 0.56), total sleep time (g = 0.33), and sleep onset latency (g = 0.32), but non-significant effects emerged for daytime sleepiness, dysfunctional beliefs about sleep, sleep efficiency, sleep hygiene, and wake after sleep onset.”
  • Attrition. “The pooled dropout rate from app conditions was 13.1%… which was significantly higher than control conditions (OR = 1.78…).”

A few thoughts:

1. This is a good paper and a relevant topic, published in a solid journal.

2. The main finding in a sentence: “findings from the present meta-analysis show that apps – primarily CBT-based – can effectively reduce symptoms of insomnia and sleep disturbances…”

3. Apps for insomnia seem to be a good way to improve access to care for many – the best of digital mental health, relevant in high- and low-income countries.

4. Looking for an app to incorporate into your practice based on this study? CBT-I Coach, developed by US Veterans Affairs and included in the meta-analysis, is free and offers many features. Monin and Buysse, for the record, mention Sleepio and Sleep Reset; both have fees. 

5. Like all studies, there are limitations. The authors note several, including that most trials didn’t include follow up, and thus didn’t give indication of sustainability.

The full Sleep Med study can be found here:

https://www.sciencedirect.com/science/article/pii/S1389945724003964

Selection 3: “By sleeping when everyone else is awake I cured my insomnia

Joanna Cannon

The Guardian, 31 December 2023

‘Why don’t you go to sleep when normal people do?’ This is a question asked of me on countless occasions. The last time was in a radio interview and I was about to give my usual self-deprecating comments about the joys of not being normal, when I took a breath and replied, ‘Because I don’t want to.’ It really is that simple. Going to bed at 5pm and getting up just after midnight suits me. I enjoy the peace and quiet. My productivity levels soar. It’s just a shame other people find it so difficult to accept. I’m not entirely sure why. I do exactly what everyone else does, I just do it about seven hours earlier. Around the time most of the country is pouring milk on their Weetabix, I’m chopping garlic and frying mushrooms for my lunch…

So begins an essay by Dr. Cannon.

She describes her day. “The day always begins with a 1am breakfast before a long walk with my dog, then I start my working day. Working from home makes it all too easy to creep into the world of permanent loungewear, so I try to make the effort and dress as if I were going out to an office. It can feel strange, switching on my computer and settling down to write in the dark, but it doesn’t seem long before the rest of the world wakes up. My office looks out over the town and I see lights appear as the new day begins. I break for lunch around 8am, then go back to my desk.”

She notes the impracticality of her approach. “Of course, this upside-down life is fine when you’re operating as a one-person army, but when I have social commitments or book events, I need to re-integrate into a ‘normal’ timetable.”

She was always a troubled sleeper, but life really changed in medical school. “A daily five-hour round trip to Leicester medical school meant I had to wake even earlier than the crack of dawn and as the course became more and more demanding and the clinical situations I witnessed increasingly distressing, that couple of hours of solitude I had each morning became integral to good mental health.”

“This habit continued long after I left the wards behind, but I often still struggled with getting to sleep. I would have long periods of insomnia, or I found I fall asleep, only to wake a couple of hours later still exhausted but unable to doze off again. My body was tired, but my mind usually failed to cooperate, and sleeplessness followed me around for most of my adult life.”

A few thoughts:

1. This is a good essay.

2. Though Dr. Cannon is satisfied with the outcome, her approach comes with significant costs. It’s tough to see how a lawyer or factory worker could so radically shift their sleep cycles.

3. How many of us have harmed our sleep patterns with the rigors of training?

The full Guardian essay can be found here:

https://www.theguardian.com/lifeandstyle/2023/dec/31/by-sleeping-when-everyone-else-is-awake-i-cured-my-insomnia-joanna-cannon

Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.