CNS 17: Pharmacotherapy of Insomnia

In this discussion, we will talk about different types of insomnia, sleep hygiene strategies, and pharmacologic options.

Insomnia Overview

Sleep is important! Insufficient sleep has been shown to lead to a multitude of health problems. When someone is unable to obtain sufficient sleep during the inability of fall asleep or stay asleep, it is called insomnia.

Insomnia is very common. Most are considered to be short-term. It is twice as common in females and in those who are unemployed or from lower socioeconomic status. The presentation of insomnia differ by ages as well. In younger adults, they tend to have difficulty falling asleep. In older adults, they tend to have difficulty staying asleep.

Primary VS. Secondary

Primary insomnia can be due several different factors that are not a result of another illness. It can be due to hyperarousal state, increased metabolic rate, or sensitivity to noise, temperature, and anxiety

Secondary insomnia is an insomnia that is a result of another illnesses or disorders.

Treatment Goals

The primary goal of the treatment is to improve quality of life, reduce daytime consequences and reduce the fear and anxiety about being unable to sleep. In trying to achieve this, we want to use the lowest possible doses for the shortest duration of time in order to avoid any adverse effects.

Treatment Approach

Sleep hygiene is the single-most effective treatment. This includes the incorporation of build good sleeping habits, such as exercising, avoiding daytime nap, using sleep/wake schedule, and avoiding blue light from electronics.

If this doesn’t work, we want to look at the the severity of insomnia, assess the underlying causes, and treatment history.

When determining which pharmacologic treatments to move forward with, it is important to identify which type of insomnia the patient is experiencing. The patient may have problem with sleep initiation, sleep maintenance, or both.

Pharmacologic Options

Benzodiazepines

The idea behind the use of BZDs is to increase the volume of GABA, which causes relaxation and allow the patient to fall asleep.

If long-acting BZDs, such as temazepam, are used. It is effective for both sleep initiation and sleep maintenance. One caveat is that patients who use BZDs to fall asleep tend to have an increased in non-REM state and a decreased in REM state, which resulted in less restful sleep. This is why BZDs are not the preferred option for insomnia even though they help both initiation and maintenance.

Two of the most common BZDs used for insomnia are

  • Triazolam (0.125-0.25mg) – for sleep initiation
  • Temazepam (7.5-15mg) – for sleep initiation and sleep maintenance

The use of BZDs in elderly should be with caution because of the potential exaggeration of adverse effects. Please refer to previous CNS section for adverse reactions of BZDs.

Z-Drugs (non-benzodiazepine)

These medications are pretty much BZDs, but with modified binding to the receptor. They bind more loose, and are able to only get the insomnia affect of BZDs. This means that the number of side effect go down significantly.

One caveat is that even thought the number of BZD side effects goes down, they have some additional effects, such as complex sleep behavior (doing things in sleep that you shouldn’t be doing).

Regardless of this, they are still a better option than BZDs most of the time. We still want to be cautious in the use of these in elderly for the same reasons as BZDs. Below are some of the Z-drugs:

  • Zolpidem (Ambien)
    • Useful for both initiation and maintenance
    • It is recommended to dose lower in women (5mg vs 10mg for IR formulation), but this is not really seen in practice.
    • The ER formulation is useful in helping patients stay asleep.
    • The SL formulation is useful in helping patients go back to sleep if they wake up in the middle of the night. Faster on, and faster off than the IR and ER.
    • Caution:
      • There seems to be a lack of efficacy over time.
      • Amnesia and headache are potential ADRs.
      • Complex sleep behaviors
      • Make sure that patients have at least 7-8 hours of sleep planned
  • Zaleplon (Sonata) – 5-10mg QHS (20mg)
    • Useful for initiation and middle-of-the-night awakenings
    • It comes on quick, and come off quick (Just like zolpidem SL). Because of this, it’s not really helpful in maintaining sleep.
    • It has less side effects than zolpidem, but still effect dizziness and headache.
  • Eszopiclone (Lunesta) – 1mg QHS (3mg)
    • Useful for both maintenance and early morning awakening
    • Caution
      • Make sure the patients have at least 7-8 hours of sleep planned
      • Daytime somnolence
      • Unpleasant taste
      • Dry mouth

Orexin Receptor Antagonists

These medications are DORAs – dual orexin receptor antagonists. They are effective for both initiation and maintenance. Both available options are schedule IV.

  • Suvorexant (Belsomra) – 10-20mg QHS
  • Lemborexant (DayVigo) – 5-10mg QHS

Caution:

  • Daytime somnolence
  • Narcolepsy-like presentation (because we’re fiddling with the same system the cause narcolepsy)
  • Can potentially worsen depression presentations

Melatonin Receptor Agonist

There are agents to potentiate the MT1 and MT2 on the SCN. The idea is that if you agonize these receptors at a specific time before bed, you can get those circadian rhythm where you want to be.

This is useful in initiation, not so much maintenance.

One good thing is that they are one of the only ones that do not cause respiratory depression. So, it is recommended for patients with sleep apnea or COPD.

Ramelteon (Razerem) 8mg QHS is the only agent in this class. ADRs include headache, dizziness, and somnolence.

Sedating Anitdepressants

These medications are useful if the patients have co-morbidities. Kill two birds with one stone deal.

They are more effective in maintenance of sleep.

Doxepin is approved fro sleep maintenance. But consider nortriptyline in elderly because it may have less anticholinergic side effects.

Remember that mirtazapine can be quite sedating, and weight gain can be significant. Also, interesting fact is over 15mg, mirtazapine starts to get NE effect, and sedating effect can be a little iffy.

Trazodone is the most commonly used medication for the treatment of insomnia. It’s usually dosed 25-100mg for sleep maintenance. At this low dose, trazodone has close to no anti-depressive effect.

Antihistamine

Antihistamine is available in so many OTC products. We definitely need to keep an eye on this. Elderly can still experience anticholinergic side effects. Patients can develop tolerant if they take every night for at least 2 weeks.

Hydroxyzine is used as short-term therapy for insomnia (off-label).

Alternative Therapies

Melatonin can help with sleep initiation. This is a reasonable attempt, but it is not helpful in maintenance. The patient should be started on 1-5mg daily 1-2 hours before bed.

Avoid melatonin derived from animal sources because there was an incidence of mad cow disease spread from this. If you’re taking melatonin, go with synthetic melatonin.

Another supplement option is valerian. It is advertised to help with sleep and anxiety. There is not a lot of evidence. Just don’t do it.

How to Choose Therapy:

Sleep hygiene first, always. Don’t just give them list, but choose a particular habit to work on.

In young, healthy patients, we can go with BZDs or Z-drug first-line. Try to go with the lowest dose for the shortest duration possible.

In patients with comorbidities and secondary insomnia, focus on treating the underlying causes. For example, in COPD, try using ramelteon and melatonin.

There is no good option for the elderly. The best options would be ramelteon and melatonin, but these do not always work because most patients have problems with sleep maintenance, not sleep initiation.

Leave a Reply

Your email address will not be published. Required fields are marked *