Sedatives, Hypnotics, and Insomnia Management

Hi, and welcome to this video on insomnia management!

Insomnia is the prolonged difficulty of falling asleep or staying asleep long enough to feel rested. It is a result of many varied causes, including poor sleep habits, depression, anxiety, pain, illness, changes in lifestyle or environment, and various medications. Insomnia that lasts from one night to a few weeks is considered acute insomnia. When insomnia lasts longer than a month, it is called chronic insomnia. Insomnia is defined by the American Academy of Sleep Medicine as the subjective perception of difficulty with sleep initiation, duration, consolidation, or quality that occurs despite adequate opportunity for sleep, and that results in some form of daytime impairment. When a patient has insomnia, it is best to start with nonpharmacologic measures first to promote relaxation, rest, and sleep. Some good sleep habits to teach patients include:

• Staying on a sleep schedule. This involves going to sleep and getting up about the same time each day. The patient should also avoid taking naps during the day, which may make them less sleepy at night.
• Avoiding caffeine, nicotine, and alcohol late in the day. Caffeine and nicotine are stimulants, making it difficult to fall asleep; alcohol interferes with sleep quality by causing waking in the night.
• Avoiding the use of electronic devices that give off light before bed.
• Getting regular exercise, preferably in the morning or at least 3-4 hours before bedtime.
• Avoiding eating a heavy meal late in the day.
• Making the bedroom comfortable—dark, quiet, comfortable temperature—if needed, they should use earplugs, white noise, or a sleeping mask
• Following a bedtime routine to help relax before sleep.

Some herbal supplements can also be helpful to treat insomnia.

• Melatonin is a natural hormone secreted by the pineal gland that helps maintain the wake-sleep cycle. Environmental light at night, such as from smartphones or TV, blocks the production of melatonin, leading to sleep disturbances. Melatonin production is stimulated by darkness, peaking between 11 pm and 3 am. Melatonin is made synthetically to mimic the effects of the natural hormone, and it is available over the counter.
• Valerian is an herbal supplement that acts like a sedative on the brain and nervous system to improve sleep quality.

Behavioral intervention or natural supplements are the preferred treatment for insomnia, but some patients may require pharmacologic therapy. It is critical to understand the benefits and risks of medications used to treat insomnia. Medications used to treat insomnia include Gamma-aminobutyric acid (GABA) agonists, melatonin agonists, Dual orexin receptor antagonists (DORAs), and other hypnotic drugs. GABA is a naturally occurring amino acid that works as a neurotransmitter in the brain, blocking certain brain signals and decreasing activity in the nervous system. When GABA attaches to a GABA receptor in the brain, it produces a calming effect, allowing the body and mind to relax and fall asleep and to sleep soundly throughout the night. Low GABA activity is linked to insomnia and disrupted sleep. Benzodiazepines are a class of drugs that stimulate GABA receptors, causing sedation, decreased anxiety, muscle relaxation, and retrograde amnesia.

Benzodiazepine Hypnotics

There are five older benzodiazepine hypnotics used to treat insomnia: temazepam, triazolam, quazepam, estazolam, and flurazepam; however, they should not be a first-line drug choice. Side effects can include daytime drowsiness, dizziness, and physical problems, such as falling, especially in older people. Contraindications include severe respiratory disorders, severe liver or kidney disease, history of alcohol or other drug abuse, pregnancy/breastfeeding, sleep apnea, and hypersensitivity reactions. Extreme caution must be taken when given with other CNS depressant drugs. There is also a high risk of developing physical dependence to benzodiazepines. After just a few weeks of therapy, patients often have rebound insomnia and increased anxiety. Long-term users report severe withdrawal symptoms after stopping the drug. To prevent withdrawal symptoms, the drug should be tapered in dose and gradually discontinued. Toxic effects of benzodiazepines include excessive sedation, respiratory depression, and coma. Flumazenil (Romazicon) is an antidote for benzodiazepines that reverses toxicity. Benzodiazepines are generally not recommended due to their high abuse potential and the availability of better alternatives.

Nonbenzodiazepine hypnotics

Nonbenzodiazepine hypnotics are the most commonly prescribed medications for insomnia, also known as the “z-drugs”: zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). Like benzodiazepines, the z-drugs also bind to the GABA receptor, but they bind more selectively, primarily targeting the sedative effect rather than the anxiolytic effect. Ambien is the most commonly prescribed nonbenzodiazepine hypnotic, and it should not be taken for more than 10 days. Sonata is approved for the short-term treatment of insomnia (7-10 days) but is contraindicated in patients with hypersensitivity reactions and during lactation. It should be used cautiously during pregnancy, for patients with depression, and for those with impaired hepatic or respiratory function. Lunesta increases total sleep time and reduces the amount of time needed to fall asleep. It is approved for long-term use and may be taken up to 12 months. Melatonin regulates the sleep-wake cycle, and decreased production can contribute to insomnia. Melatonin production decreases with age and gets disrupted with changing time zones and shift work. Ramelteon (Rozerem) is a melatonin agonist and is approved for long-term use. Rozerem binds to melatonin receptors in the CNS and is thought to play a role in maintaining the circadian rhythm, helping to regulate the normal sleep-wake cycle. It is the only non-controlled hypnotic, it has few adverse effects, and it does not produce physical dependence.

Dual Orexin Receptor Antagonists (DORAs)

Orexins are a type of neurotransmitter produced in the hypothalamus that play an important role in sleep, energy metabolism, and mood. Lemborexant and suvorexant are medications that have antagonist activity at both of the orexin receptors and, therefore, facilitate sleep by decreasing the wake drive. They have minimal side effects but should be avoided in patients with severe hepatic impairment and narcolepsy. Some patients may experience drowsiness the morning after taking and should not drive if they do not feel fully alert.

Other Hypnotic Drugs

Other hypnotic drugs used to treat insomnia include antidepressants, antihistamines, and antipsychotics. Antidepressants are often used for their sedative effects, but the only one that is FDA-approved is the tricyclic antidepressant doxepin (Silenor). Doxepin functions as a histamine antagonist, producing a sedating effect. Several other antidepressants are also used off-label to treat insomnia, including trazodone, mirtazapine (Remeron), amitriptyline (Elavil), and nortriptyline (Pamelor). These medications should only be considered if there is another indication besides insomnia. Antihistamines such as diphenhydramine (Benadryl) and doxylamine are available over the counter for the treatment of pregnancy-related insomnia. These sedating antihistamines have significant anticholinergic effects and should be avoided in patients with glaucoma or urinary retention. Several antipsychotic medications are used off-label to treat insomnia, but they should only be used if the patient has some other indication, such as bipolar disorder. Patient teaching guidelines for sedative-hypnotic drugs include:

• Avoiding use of the drugs every night—taking them intermittently helps maintain effectiveness of the drug and reduces risks of drug abuse and dependence.
• Not performing tasks that require alertness, such as driving or operating machinery, if drowsy from medication. Routine activities can be potentially hazardous due to impaired mental and physical functioning, especially during the first few days of drug use.
• Avoiding alcohol and other depressant drugs while taking sedative-hypnotic drugs, because combining them produces additive depression and may lead to excessive drowsiness, difficulty breathing, traumatic injuries, and other potential adverse effects.

Let’s look at a couple of questions for review:

Review Questions

1. The most commonly prescribed medication for insomnia is

1. Antihistamines
2. Benzodiazepines
3. Nonbenzodiazepine hypnotics
4. Antidepressants

2. Which of the following is not a good sleep habit?

1. Get regular exercise, preferably in the evening
2. Avoid caffeine late in the day
3. Avoid alcohol late in the day
4. Follow a bedtime routine to help relax

Thanks for watching, and happy studying!