Sleep interventions: what’s out there?

May 31, 2024

by Ryan Neely, Ph.D

Having trouble sleeping lately? At least you can (not) rest assured that you aren’t alone. Approximately 30-40% of adults in the United States report symptoms of insomnia every year and the number is rising1. A recent study estimated that the economic costs of insomnia exceed $100 billion per year when accounting for things like poor workplace performance, increased risk of accidents, and healthcare costs.2 For many poor sleepers, the question of how to get better sleep is a complicated one. Tools for improving sleep are about as numerous as the different types of sleep disturbances- which is to say, a lot. In this post we’ll break down several different categories of interventions that are meant to improve sleep, and discuss the pros and cons of each. To keep things manageable, we’ll take a look at the following types of treatments:

Pharmaceuticals
Behavioral interventions
Sound-based approaches (like music or white noise)
Neuromodulation

A quick note here on semantics: there are many sleep disorders that can result in poor sleep quality, but for our purposes we’ll focus on insomnia, which is the most common. The official definition of insomnia is difficulty initiating or maintaining sleep that results in a daytime consequence.

Pharmaceutical treatments for insomnia

There are many drugs intended to treat insomnia, including over-the-counter treatments as well as a number of prescription medications. Some of these drugs have been in use for decades, while others that target new biological mechanisms have just been recently approved. Over-the-counter medications are a mixed bag in terms of how they affect your brain and nervous system. Diphenhydramine (AKA Benadryl or Unisom) is an antihistamine, meaning it blocks the action of histamine, which regulates local activity of the immune system. For this reason, diphenhydramine is primarily used to treat allergy symptoms. However, histamine pulls double-duty as a neurotransmitter, so it can also cause drowsiness via its effects in the brain. Melatonin is also a common OTC medication with a totally different mechanism of action. Melatonin is a hormone produced by the brain in response to darkness (and its production is suppressed by light exposure - especially in the blue range of the visible spectrum). Although it has a known role in promoting sleep, the American Academy of Sleep Medicine (AASM) and the American College of Physicians both find that there isn’t strong enough evidence to recommend its use.

Over in the world of prescribed drugs, things get even more colorful. Benzodiazepines come in a number of varieties, of which the short-acting types tend to be most commonly prescribed for sleep. Temazepam (Restoril) is an example of this drug class. Benzodiazepines act by increasing the activity of GABA, an inhibitory neurotransmitter in the brain, resulting in a sedative effect. However, benzodiazepines aren’t very selective at hitting their target. For this and other reasons, they have an increased potential for abuse, dependence, and unwanted side effects. The “Z drugs,” developed more recently in the 1990’s, (such as Zolpidem (Ambien) and Zaleplon (Sonata) work in a similar way (by targeting GABA transmission), but are technically a different drug class. Although they are increasingly prescribed as an alternative to benzodiazepines, there is no evidence to suggest they have a better safety and side effect profile3. Antidepressants can also be prescribed for insomnia symptoms, often at lower doses than used to treat depression. Doxepin (Silenor) is an example of an antidepressant used to treat insomnia. It tends to be less effective at promoting sleep, but has been shown to help people stay asleep4.

One of the most recent drug classes to be introduced is the orexin receptor antagonists, like suvorexant (Belsomra). Unlike most of the drugs mentioned above, which enhance sleep-promoting neurotransmission, orexin receptor antagonists work by reducing activity in neural circuits that promote wakefulness. These drugs may have a lower potential for abuse than benzodiazepines and Z-drugs, although their relative newness means that many of them can be quite expensive relative to others for which generics are available.

Given the variety of options available, which sleep drugs are the most effective? The answer is complicated, and probably depends on the individual. A recent meta-analysis of 170 clinical trials across 30 different drugs5 found mixed results - though many drugs did improve symptoms, there was often a tradeoff between efficacy and side effects, with many effective drugs also having lower tolerability. It’s hard to predict which of these drugs might be best for any given person, and any choice about medication should be done in consultation with your doctor.

Behavioral Interventions

“Behavioral interventions” is a way of saying “things you can do” to improve sleep. Early approaches included hypnosis and relaxation training. In the 1980s, sleep restriction was introduced as a treatment option. Today, the recommended approach is “cognitive behavioral therapy for insomnia” (CBT-I), which combines a number of different behavioral therapies and cognitive therapy techniques6. CBT-I involves promoting sleep hygiene, which means reducing behaviors that impair sleep (such as using electronic devices in bed). Additionally, this approach typically involves some form of sleep scheduling to enforce consistent bed and wake times, and reduce the amount of time spent awake in bed. Finally, CBT-I may include cognitive therapy and relaxation training administered by a therapist. Although it does require a number of behavioral changes on the part of the patient, there is good evidence that CBT-I works at least as well as sleep drugs in the short term, and possibly better in the long term. However, it is recommended that all aspects of CBT-I are followed rather than just a single component in order to have the best outcome6.

Sound-based approaches

Many individuals use ambient sounds such as fans, white noise machines, or soft music to help them fall asleep. The research on this topic is limited, and has only been tested in small groups of people. However, one study did find evidence that participants who listened to broadband white noise fell asleep faster compared to normal environmental noise7. This suggests that using a white noise machine to mask road noise or other sleep-disrupting sounds may be a good strategy. Music is another form of sounds which are often used to promote sleep, with some music specifically marketed for this purpose. One study examined subjects in a sleep lab while they listened to commercially marketed “sleep music,” non-musical tones, or nothing. The researchers found no difference in any sleep metric between conditions, suggesting that at least in this case the music was not helpful. However, they noted that it was not possible to test all varieties and genres of music in this setting8.

Neuromodulation

One of the newer and more exciting approaches to sleep therapy is neuromodulation. While companies like Elon Musk’s Neuralink or Blackrock Microsystems are designing implants for the brain to overcome paralysis, other non-invasive approaches to interfacing with the brain are being developed to address sleep. At Elemind Technologies, we are building on decades of foundational research on neural oscillations to build active systems that interact with brainwaves in real-time to promote healthy sleep. During deep sleep (AKA “Slow-Wave” sleep), the electrical activity of the brain is dominated by slow (~1 cycle/second) oscillations. A separate observation is that sensory stimuli (such as a flash of light or pulse of sound) also produce short-lived electrical “waves” of their own. In 2013, a group of researchers asked whether they could combine these two concepts to enhance sleep. By timing the “wave” generated by a sound pulse so that it occurred in tandem with a wave generated during deep sleep, they were able to enhance the slow wave rhythms, but also improve memory consolidation9, findings which have since been replicated10,11. At Elemind, we’ve designed a comfortable, convenient headband that can measure and react to brainwaves in real-time and deliver auditory stimulation to enhance deep sleep slow waves, just like these laboratory studies. However, we’ve taken things a step further by also targeting fast “alpha” oscillations (~10 cycles/second) that dominate while you’re trying to fall asleep and dissipate once you’ve entered the early stages of sleep. Studies have shown that these alpha waves are associated with states of hyper-arousal and are elevated in insomniacs12, but due to the speed of these signals, the technologies needed to process them in real-time have been lacking. The Elemind ENMod system is capable of tracking these fast brainwaves with high precision, but unlike for sleep slow waves, our device delivers sounds that interfere with alpha waves, promoting a faster sleep onset13. And, because we’re already measuring your brainwaves, we can track sleep stages directly from the brain itself!

Conclusion

There are many interventions designed to promote sleep (including some that we didn’t cover here). Any one strategy will have a unique balance of efficacy, side effects, and effort needed from the user to make it successful. At Elemind, we’re putting decades of research to work to develop the next generation of tools to improve and track sleep while minimizing side effects and the need for training or effort by the user (getting a good night’s sleep is hard enough already!). We see where existing sleep aids fall short, and are using our growing trove of sleep data recorded from real brains to understand how we can tailor our approach to an individual’s unique neural signature to create the biggest benefit for the most users. We’re excited by the benefits we’ve already seen in the lab and at home, and can’t wait to help more people looking to improve their sleep health. We can’t predict what the future holds, but we feel confident that it will involve better sleep!

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