Evidence-Based Reviews

Treating chronic insomnia: An alternating medication strategy

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Alternating between 2 agents from different classes can help avoid tolerance/tachyphylaxis.


 

References

Patients with chronic insomnia that does not improve with nonpharmacologic techniques often develop tolerance to sedative medications (benzodiazepines) prescribed for nightly use. When nonbenzodiazepine medications are used, tachyphylaxis can develop and these medications no longer initiate or maintain sleep. Strategies that alternate between these 2 types of agents are simple to follow and may allow patients to maintain sensitivity to both types of medications. In this article, I review the types, causes, evaluation, and treatment of insomnia; describe an alternating medication strategy to help patients avoid developing tolerance/tachyphylaxis; and present 3 fictional case vignettes to illustrate this approach.

A common, troubling condition

Insomnia is a common problem among psychiatric patients. Approximately 30% to 50% of adults experience occasional, short-term (<3 months) insomnia, and 5% to 10% experience chronic (≥3 months) insomnia,1 with associated negative impacts on health and quality of life. Insomnia is sometimes primary and may have a hereditary component, but more often is associated with medical, neurologic, or psychiatric disorders.

Patterns of insomnia include difficulty falling asleep (initial or sleep-onset insomnia), remaining asleep (middle or sleep-maintenance insomnia), or falling back asleep after early awakening (late or sleep-offset insomnia). Sleep-onset insomnia correlates with high levels of anxiety and worrying, but once asleep, patients usually stay asleep. Sleep-maintenance problems involve multiple awakenings after falling asleep and taking hours to fall back to sleep. These patients experience inadequate sleep when they must wake up early for school or work. Early-awakening patients report feeling wide awake by 4 to 5 am and being unable to get back to sleep.

Caffeine is an important consideration for patients with sleep difficulties. Its use is widespread in much of the world, whether ingested as coffee, tea, in soft drinks, or in “energy” drinks that may contain as much as 200 mg of caffeine (twice the amount in a typical cup of brewed coffee). Caffeine may also be ingested as an ingredient of medications for headache or migraine. While some individuals maintain that they can fall asleep easily after drinking caffeinated coffee, many may not recognize the amount of caffeine they consume and its negative impact on sleep.2 Author Michael Pollan stopped use of all caffeine and reported on the surprising positive effect on his sleep.3

Patients with mood, anxiety, or psychotic disorders are likely to experience insomnia intermittently or chronically, and insomnia predisposes some individuals to develop mood and anxiety symptoms.4 Patients with insomnia often experience anxiety focused on a fear of not getting adequate sleep, which creates a vicious cycle in which hyperarousal associated with fear of not sleeping complicates other causes of insomnia. A patient’s chronotype (preference for the time of day in which they carry out activities vs sleeping) also may play a role in sleep difficulties (Box5).

Box

Early birds vs night owls

Chronotypes—the expression of circadian rhythmicity in an individual—have been studied extensively.5 Psychiatrists may encounter patients who sleep most of the day and stay awake at night, those who sleep up to 20 hours per day, and those who sleep <4 hours in 24 hours. Patients typically know which category they fall into. The early bird typically is awake by 6 or 7 am, remains alert through most of the day, and feels sleepy by 10 pm. The usual diurnal variation in cortisol, with peaks at 7 am and 7 pm and nadirs at 1 pm and 1 am, correspond with the early bird’s habits.

Night owls typically report feeling exhausted and irritable in the early morning; prefer to sleep past noon; feel energized around dark, when they can do their best studying, concentrating, etc; and do not feel sleepy until early morning. While this night owl pattern is a natural variation and not necessarily associated with psychiatric illness, patients with mood disorders frequently have chaotic sleep patterns that may not conform to a pattern. Night owls maintain the same diurnal pattern of cortisol secretion as early birds.

Certain medications may contribute to insomnia, particularly stimulants. It is important to understand and explain to patients the time frame during which immediate-release or extended-release (ER) stimulants are active, which varies in individuals depending on liver enzyme activity. Other commonly used psychotropic medications—including bupropion, modafinil, armodafinil, atomoxetine, amphetamine salts, and methylphenidate—may interfere with sleep if used later in the day.6

Patients typically do not mention their use of alcohol and/or marijuana unless asked. Those who are binge drinkers or alcohol-dependent may expect alcohol to help them fall asleep, but usually find their sleep is disrupted and difficult to maintain. Patients may use marijuana to help them sleep, particularly marijuana high in tetrahydrocannabinol (THC). While it may help with sleep initiation, THC can disrupt sleep maintenance. Cannabidiol does not have intrinsic sedating effects and may even interfere with sleep.7,8

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