What are the different sleep aids, their mechanisms of action, and effects on the body?

From the Guidelines

Sleep aids should be chosen based on their efficacy, safety, and the specific needs of the patient, with prescription medications, over-the-counter options, and natural remedies each having different mechanisms of action and potential benefits and risks, as outlined in the American Academy of Sleep Medicine clinical practice guideline 1.

Types of Sleep Aids

Sleep aids can be categorized into several types, including:

• Prescription medications, such as benzodiazepines, non-benzodiazepine hypnotics, and melatonin receptor agonists, which work by enhancing GABA activity, targeting specific GABA receptors, or mimicking natural sleep hormones, respectively.
• Over-the-counter options, including antihistamines and synthetic melatonin supplements, which block histamine to cause drowsiness or help regulate sleep-wake cycles.
• Natural remedies, such as valerian root, chamomile, and lavender, which have mild sedative effects.

Mechanisms of Action

Each type of sleep aid works differently in the body to promote sleep. For example:

• Benzodiazepines, like Valium, enhance GABA activity to slow brain activity, while non-benzodiazepine hypnotics, like Ambien, target specific GABA receptors with fewer side effects.
• Melatonin receptor agonists, like Ramelteon, mimic natural sleep hormone to regulate sleep-wake cycles.
• Antihistamines, like Benadryl, block histamine to cause drowsiness, but can cause daytime drowsiness and are not recommended for long-term use.
• Synthetic melatonin supplements can help regulate sleep-wake cycles, but are generally most effective for circadian rhythm issues rather than insomnia.

Recommendations

The American Academy of Sleep Medicine recommends that sleep aids be used in conjunction with good sleep hygiene practices, such as maintaining a regular sleep schedule, avoiding screens before bed, and creating a comfortable sleep environment, and that patients with chronic insomnia should receive cognitive behavioral therapy for insomnia (CBT-I) as a primary intervention, with medications considered mainly in patients who are unable to access or respond to CBT-I 1. It is also important to consult a healthcare provider before starting any sleep medication, especially if you have other health conditions or take other medications.

From the FDA Drug Label

1. Clinical Pharmacology 12.1 Mechanism of Action Zolpidem is a GABA A receptor positive modulator presumed to exert its therapeutic effects in the short-term treatment of insomnia through binding to the benzodiazepine site of α1 subunit containing GABA A receptors, increasing the frequency of chloride channel opening resulting in the inhibition of neuronal excitation. CLINICAL STUDIES SECTION The effect of eszopiclone on reducing sleep latency and improving sleep maintenance was established in studies with 2100 subjects (ages 18 to 86) with chronic and transient insomnia in six placebo-controlled trials of up to 6 months’ duration.

Different Sleep Aids and How They Differ and Work in the Body:

• Zolpidem: works by binding to the benzodiazepine site of α1 subunit containing GABA A receptors, increasing the frequency of chloride channel opening resulting in the inhibition of neuronal excitation 2.
• Eszopiclone: reduces sleep latency and improves sleep maintenance by an unknown mechanism, but is believed to be related to its ability to modulate the activity of GABA, a neurotransmitter involved in sleep regulation 3. Key Differences:
• Mechanism of Action: Zolpidem is a GABA A receptor positive modulator, while Eszopiclone's mechanism is not fully understood.
• Pharmacokinetics: Zolpidem has a short elimination half-life, while Eszopiclone's half-life is not specified in the provided text.
• Efficacy: Both Zolpidem and Eszopiclone have been shown to be effective in reducing sleep latency and improving sleep maintenance in clinical trials 2, 2, 3.

From the Research

Sleep Aids and Their Differences

• Non-pharmacological interventions:
  • Cognitive Behavioral Therapy for Insomnia (CBT-i) 4
  • Relaxation techniques 5
  • Sleep hygiene improvements 5
  • Daytime bright light exposure 5
  • Resistance Training 6
  • Yoga 6
  • Music 6
  • Light therapy 6
• Pharmacological interventions:
  • Zolpidem 7
  • Eszopiclone 8

How Sleep Aids Work in the Body

• CBT-i: helps patients learn how to support and promote the body's natural sleep mechanism by addressing sleep consolidation, stimulus control, cognitive restructuring, sleep hygiene, and relaxation techniques 4
• Zolpidem: works as a non-benzodiazepine hypnotic to induce sleep, but has various adverse effects such as increased risk of falls, hip fractures, and CNS-related symptoms 7
• Eszopiclone: used in conjunction with CBT-i to improve sleep quality and quantity in patients with sleep disorders, particularly those transferred out of the intensive care unit 8
• Non-pharmacological interventions: have been shown to improve sleep quality and quantity, with varying degrees of effectiveness, and may be used as alternative or complementary therapies to pharmacological interventions 6, 5

Comparison of Sleep Aids

• CBT-i has been shown to be as effective as sleep medication, with no side effects and long-term improvements in sleep quality 4
• Zolpidem has a wide range of adverse effects, but may be a suitable pharmacological treatment for insomnia when used in conjunction with CBT-i and with careful consideration of the patient's physical and psychiatric risks 7
• Eszopiclone has been shown to be effective in improving sleep quality and quantity when used in conjunction with CBT-i, particularly in patients transferred out of the intensive care unit 8
• Non-pharmacological interventions have been shown to improve sleep quality and quantity, but the evidence is not yet strong enough to guide clinical practice, and further studies are needed to determine their effectiveness 6, 5