At least 1 out of 3 Americans reports having sleep troubles. Many people do not get evaluated for their sleep problems and instead seek out a quick fix in the form of a prescription drug. According to the New York Times, 60 million prescriptions for sleep aids were handed out in 2011, a number that represented a 20 percent spike from 2006.
In this second of a 2-part Q & A with sleep expert Maha Ahmad, MD, MMSc (pictured), Associate Director of the Sleep Disorders Institute in New York, MedShadow explores the most widely used drugs to treat insomnia and their side effects.
Q: Many people take OTC antihistamines — Benadryl, for example, to treat their insomnia. The FDA recently warned that the drugs’ sedating effects may linger into the next day. What are the side effects of these OTC drugs?
A: The next morning, people may have difficulty waking up. They may experience drowsiness and impaired alertness. With antihistamines, additional side effects include things like dry mouth, urinary retention, constipation, and orthostatic hypotension. Orthostatic hypotension refers to a drop in blood pressure upon standing, which may result in light-headedness or dizziness.
Q: Many people turn to prescription medications to treat their insomnia. Zolpidem is the active ingredient in the most popular prescription drugs (Ambien, Edluar, Zolpimist, Intermezzo, and Ambien CR). The FDA has recommended a lower dosage of this medication for women. Why?
A: It’s because of the morning impairment. The FDA is concerned about driving because small amounts of these medications may remain in your system in the morning. But please keep in mind that people who don’t sleep well because of untreated insomnia may also be impaired while driving! You have to keep all of this in perspective. The reason the recommended doses were lowered for women is that women tend to metabolize zolpidem more slowly than men. In other words, zolpidem takes longer to be eliminated from the bodies of women than of men.
Q: What’s the new recommended dosage for women?
A: In the drug’s immediate release form of Ambien, the recommended dose for women is 5 mg, down from 10 mg. In the extended-release form of Ambien CR, the recommended dose for women is now 6.25 mg instead of 12.5 mg.
Q: What about men?
A: Men also may want to consider a lower dose if the lower dosage works for them.
Q: Though sleep aids containing zolpidem are the focus of the FDA advisory, the agency also says it’s investigating other drugs similar to those as zolpidem. Are you hearing about the same type of prolonged drowsiness among patients taking Lunesta (eszopiclone) and Sonata (zaleplon)?
A: Yes, this can be true for many hypnotics (prescription insomnia medications that include benzodiazepines such as Valium and non-benzodiazepines such as Ambien) It depends on their half-life and also how quickly a person can metabolize them. The medications with a shorter half-life are less likely to create a problem for people the next morning. The drugs with a longer half-life may remain in the system for longer, and even longer in people who metabolize drugs more slowly, such as elderly patients, women, and people taking other medications that may have an interaction with the hypnotic (such that the other medication increases the blood level of the hypnotic). The half-life of a medication is how long it takes for half of the medication to clear the body. It typically takes about 4 half-lives for 90-95% of a drug to be eliminated. So, if the half-life of a drug is 3 hours, it will take approximately 12 hours before it’s mostly out of your body.
Q: What’s the half-life of such immediate release products as Ambien, Zolpimist, Edluar, Intermezzo and Sonata?
A: Sonata has the shortest half-life: 1 hour. Ambien is between 1.4 to 4.5 hours; Intermezzo 1.4-3.6 hours; Zolpimist 1.7-8.4 hours; Edluar 1.4-4.5 hours. These are ranges. Everyone processes these drugs differently; it depends on a person’s body chemistry.
Q: What about the half-life of such extended release drugs as Ambien CR and Lunesta?
A: Lunesta’s half-life is approximately 6 hours. Ambien CR’s half-life is 1.6 to 5.5 hours.
Q: So are extended release forms more likely to generate the side effect of drowsiness, the morning hangover?
A: Yes, because they have longer half-lives, and therefore take longer to be eliminated from the body.
Q: Do you suggest that patients perhaps ask their friends or their partner how they appear to be performing the next day?
A: That’s a good idea. If the person who has taken a hypnotic doesn’t seem to have good judgment about their level of functioning in the morning, then maybe the people around them should inform them of this and make sure they avoid driving until they are fully alert.
Q: What are other common side effects that you see among patients taking these medications?
A: Headache, dizziness, nausea, and anterograde amnesia, which is a mild memory impairment for things that happen between when one takes the medication and when one goes to sleep. You also want to be careful about fall risk in elderly patients — to minimize fall risk, you want to make sure the patient takes their medication right before they get into bed, or ideally once they are already in bed and ready to go to sleep.
Q: Is is safe for people to take OTC insomnia medications—especially those containing Tylenol–for very extended periods of time? Are there any side effects?
A: With products containing Tylenol, one has to be careful about effects on the liver, so people taking these medications long-term should have this followed by their doctors.
Q: Likewise, is it safe for people to take the new generation of prescription insomnia medications, such as Ambien and Sonata, for very extended periods of time? Are there any potential side effects for people who take these drugs for years?
A: Some people with very severe or refractory insomnia do indeed take these medications for extended periods of time. They should also be followed by their physicians for regular assessment of medication effectiveness and monitoring for adverse effects. Of course, if not already done, a trial of behavioral therapy should be instituted, and these patients should continue to adhere to good sleep habits even if they use hypnotics long-term. Also, any other underlying medical conditions or sleep disorders (such as sleep apnea or restless legs syndrome), that could be exacerbating the insomnia should be properly diagnosed and treated as well.
Q: Let’s talk about less common side effects, such as confusional arousals, sleepwalking, sleep texting, sleep-eating, or sexsomnia, with no recollection for these events the next day. Is this something you see in your patient population?
A: It comes up occasionally. These are complex sleep-related behaviors, also known as parasomnias, and medications like these can trigger them. These complex behaviors are more likely to occur at higher than recommended doses, or when these medications are combined with alcohol and/or other central nervous system depressants. These complex behaviors as a side effect are not that common, but we do alert patients to it.
Q: One listed side effect is hallucinations. Is that common?
A: None of my patients have ever complained about hallucinations as a side effect of their hypnotic, but if it is listed, it must be a possibility.
Q: How should patients stop taking these drugs?
A: These medications should be tapered, they shouldn’t just be stopped. The taper should be done under the guidance of a physician. Also, when coming off of these medications a good sleep behavioral program should also be in place.
Q: What’s your best advice for treating insomnia?
A: In general, behavioral treatments are the best treatments for insomnia. Behavioral treatments can also be done alongside medication treatments. Hypnotics (many insomnia medications are called hypnotics) can also be safe and effective, but they should be prescribed under the care of a physician, ideally a sleep medicine physician. And even the higher dosages of Ambien 10 mg or Ambien CR 12.5 mg can be safe, but again, it should all be done under the guidance of a properly trained physician.
The Ambien, Lunesta, Sonata group are non-benzodiazepine allosteric modulators of the GABAA receptor. They work on the GABAA receptor like the traditional benzodiazepines, but they are more subtype specific. Therefore they have fewer side effects than their benzodiazepine predecessors. That is one reason they’re more preferable drugs for insomnia compared to the older benzodiazepines.
Facts about OTC sleep aids and newer, widely prescribed sleep medications
- Common over-the-counter (OTC) antihistamines such as Benadryl often taken for insomnia and OTC sleep aids such as Excedrin PM, Nytol and Tylenol PM that contain the antihistamine diphenhydramine can cause drowsiness to linger into the next day.
- Other side effects of diphenhydramine that may affect older people include confusion and difficulty in urinating.
- The newest prescription drugs for insomnia work on a specific brain receptor, believed to enhance sleep. These medications include Ambien, (zolpidem), Ambien CR (zolpidem extended release), Lunesta (eszopiclone), and Sonata (zaleplon). Targeting only one receptor, they are believed to have fewer side effects than benzodiazepines–older insomnia drugs that focus on multiple brain receptors.
- Benzodiazepine drugs include Ativan (lorazepam), Halcion (triazolam), Restoril (temazepam), Valium (diazepam), and Xanax (alprazolam). In addition to next-day sleepiness, their potential side effects include reduced anxiety, muscle relaxation, dizziness and memory impairment.
- Next-day drowsiness is also a potential side effect of products containing zolpidem, including Ambien, Ambien CR (extended release), Zolpimist, Edluar, and Intermezzo.
- With these products, women experience more episodes of next-day impaired alertness because their bodies take longer to clear the drugs than their male counterparts.
- With slower metabolism rates, elderly people also may experience more incidences of next-day impairment.
- Even though people may feel alert on the morning after taking these medications, they may still be impaired.
- The risk for morning impairment is highest for people taking the extended release forms of zolpidem, including Ambien CR.
- Other potential side effects for products containing zolpidem and other, similar sleep medications include mild memory impairment and sleep-driving, sleep-walking, sleep-sex and sleep-eating.
To Judge Sleep Aids, U.S. Looks at Drowsy Driving in the Morning (The New York Times)