The best prescription sleep aid is the one with the lowest risks that works for you. Sleeping aids are not a long-term solution for insomnia. Most prescribed sleeping pills are required to display a Black Box Warning due to side effects that have caused death in other patients. In addition to the serious and life-threatening side effects required in the Black Box Warning, most sleeping pills have a long list of adverse reactions from their clinical trials and post-trial reports.
The few prescription sleep aids that don’t have a Black Box Warning are relatively new. That doesn’t mean they are safer. The only thing you can be sure of is that the adverse effects haven’t been reported yet. The FDA usually mandates Black Box Warning labels after a drug is being used by patients who are not part of a clinical trial report serious adverse reactions. In plain English, this means that some people experienced serious and life-threatening side effects before the FDA required the Black Box Label. With new drugs, the full range of side effects is often unknown.
Several classifications of drugs are used as prescription sleep aids. The most common include Hypnotics, Benzodiazepines, Barbiturates, anti-depressants, Melatonin Receptor Agonists, and Serotonin Antagonists. While some drugs were developed for use as sleep aids, some are off-label drugs that are prescribed as sleep aids. Off-label drugs refers to a drug that is approved by the FDA for a different use that also has a positive effect on the off-label use for which it is prescribed. Using off label prescription drugs as sleep aids is a common practice.
Let’s take a look at the warnings, side effects, and contraindicators for the most commonly prescribed sleep aids.
Hypnotics (Non-Benzodiazepine Sedatives)
Hypnotics are prescription medications prescribed to treat insomnia, Restless Leg Syndrome (RLS) and Periodic Limb Movement Disorder. Z-drugs is another name used to refer to this GABA-A agonist that induces a sedative effect which can cause sleepiness. Although they effect the body in much the same way benzodiazepines do, they create the effect through a different mechanism.
Use: persistent problems with insomnia or problems that interfere with sleep such as RLS.
Black Box Warnings
Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur with therapy; some of these events may result in serious injuries, including death; discontinue therapy immediately if patient experiences a complex sleep behavior
All three hypnotics also include the risks of:
Worsening respiratory disease
Worsening clinical depression including suicidal thoughts and completed suicides
Psychomotor impairments the day after taking this prescription sleep aid including:
Impaired driving (especially if the patient did not sleep 7 – 8 hours after taking the dose)
When other Central Nervous System depressants (including alcohol) were also taken
Increased risk of falls including hip fractures and intracranial hemorrhage – especially among the elderly
Eszopiclone (Lunesta) and Zaleplon (Sonata)
The most common adverse effect was headaches, experienced by 38% of patients. Other side effects include amnesia, eye pain, dizziness, abdominal pain and less common side effects including tremors, hallucinations, and skin sensations with no apparent cause.
Zolpidem (Ambien, Edluar, Zolpimist, Intermezzo)
The following warnings should be considered in addition to the Black Box and other warnings:
Decreased level of consciousness
Risk of abuse – especially for individuals with a history of drug dependence
Severe anaphylactic and anaphylaxis in some patients
Behavior abnormalities including decreased inhibition, uncharacteristic aggressiveness and extroversion, bizarre behaviors, depersonalization, and agitation
Reported adverse effects also include hallucinations, and quality of life problems like headaches and less common side effects which include memory disorders, heart palpitations, depression, visual disturbances as well as some minor irritants.
Physicians will generally try a hypnotic before they prescribe benzodiazepines as a sleep aid because the side effects from benzodiazepines can be more significant.
Benzodiazepines are also used to treat anxiety and seizure disorders.
Black Box Warnings
Concomitant use of benzodiazepines and opioids may result in profound respiratory depression, coma, and death; administer concomitantly when there are no alternative options; limit dosages and durations to minimum required; monitor for signs and symptoms of respiratory depression and sedation..
The duration of the drug’s effectiveness varies by type of benzodiazepine used. The bodies of senior citizens and women may process the drug out of their system more slowly. That means the effects may last longer in those groups, which can be dangerous. Individuals with impaired liver function may also be affected for a longer period. The higher the dose, the greater the risk that adverse side effects will occur.
Cautions and Contraindicators
Benzodiazepines can cause serious side effects in the healthiest patient. When a patient already has health impairments, the danger is even higher. Patients with the following conditions or histories may not be good candidates for benzodiazepines because of increased risks:
History of drug or alcohol dependence
Respiratory impairment ( COPD, Sleep Apnea, lung diseases, etc. )
Patients with psychotic illness or depression
In addition, benzodiazepines include the following warnings:
May cause drug dependence
Central Nervous System (CNS) depression that impairs mental and physical abilities can occur
Hyperactive, aggressive, or paradoxical behavior may occur
Do not consume alcohol
Do not take other CNS depressants
May interfere with the ability to drive or operate machinery the next day
Researchers report that sleeping pills are prescribed when they should not be, due to contraindicators, so we strongly encourage you to read the package insert and look up drug interactions yourself to reduce the risk that your physician makes a mistake that you’ll end up paying a hefty price for.
The reported side effects for the various types of benzodiazepines have significant overlap and include numerous life-threatening reactions. We strongly encourage you to read the package insert, ask questions if you don’t understand everything, and avoid drug interactions. Each benzodiazepine has numerous potential side effects. The following list is for all benzodiazepines. For the specific side effects of the prescription benzodiazepine you were prescribed as a sleep aid, refer to the package insert.
Serious adverse effects of benzodiazepines that can directly or indirectly cause death include:
Central Nervous System (CNS) depression
Confusion and disorientation
Allergic reactions including anaphylaxis
Decreased level of consciousness
Worsening depression including thoughts of suicide and completed suicide
Fall risk; especially in elderly patients
Slow heart rate (Bradycardia)
Hallucinations (auditory and visual)
Increased liver transaminases (indicates potential damage to the liver)
Increase in ALP (indicator of liver or gallbladder problems)
Sleep related activities (sleep driving, sleep-cooking, sleep-eating, etc.)
Passing out due to low blood pressure
Additional adverse effects include behavioral changes, amnesia, and a long list of lesser adverse effects including trouble with urination, tremors, impotence, nausea and other quality of life issues.
Report any side affects you experience to your doctor.
Types of Benzodiazepines
Clorazepic acid (Tranxene)
Anxiety and anti-seizure medication (use for insomnia is off label).
Insomnia treatment. If increased daytime anxiety is experienced, call your doctor immediately.
Treatment for insomnia.
Prescribed for anxiety and anxiety associated with depression; use as a sleeping pill is off label. Xanax has a slow onset and continues acting for 11 – 20 hours in healthy adults. This period may be longer in elderly individuals and those with reduced liver function
Lorazepam (Ativan, Lorazepam Intensol)
Short-term insomnia treatment and anxiety medication. Off-label for chronic insomnia. This is a fast-acting prescription sleep aid.
Primarily used as a sleep aid.
Temazepam (Normison, Restoril)
Used to treat insomnia patients.
Prescribed primarily for post-operative anxiety.
Clonazepam has an intermediate onset. It is not fast acting. Used primarily for panic and seizure disorders, and off label use for REM Sleep Behavior Disorder.
Off label use for insomnia; primarily used for sedation in hospitals, anxiety, and anti-seizure needs. This is a fast-acting drug and is one of the few benzodiazepines that doesn’t report amnesia as a potential side effect.
Flurazepam hydrochloride (Dalmane)
Proscribed as a sleep aid for insomnia or trouble staying asleep as well as waking up too early.
Barbiturates are sedative hypnotics that depress Central Nervous System (CNS) function, including depressing the sensory cortex and motor activity and altering cerebellar function. Even when a patient manages to sleep using a barbiturate, researchers report that the sleep they experience isn’t as healthy or restorative as natural sleep. When patients are observed in sleep laboratories, the amount of time in the REM (rapid eye movement) phase of sleep is reduced.
REM sleep is essential for health. Individuals who sleep but don’t get sufficient REM sleep experience increased inflammation, obesity risk, and memory problems. Patients who are inhibited from any REM sleep also have an increased risk of cardiovascular disease, depression, and diabetes.
Barbiturates lose much of their ability to induce and maintain sleep with daily use for as little as two weeks.
Cautions and Contraindicators
Barbiturates may cause:
Dependence on the drug
Depression and suicidal tendencies
Withdrawal symptoms (including delirium, convulsions, and possibly, death)
Barbiturates are contraindicated for individuals who have a history of:
Severe respiratory disease
Chronic pain patients
History of drug abuse
Current pregnancy or nursing
The serious reported adverse effects all occur less than 1% of the time but include hallucinations, hepatotoxicity, CNS depression, Bradycardia, Ataxia, and numerous other side effects.
Uncommon side effects include Bradycardia, confusion, hypotension, hyperkinesia, ataxia, CNS depression, nightmares, and nervousness as well as non-serious issues such as nausea.
Pentobarbital Sodium (Nembutal) and Seconal (Seconal Sodium)
The adverse effects can be deadly including suicide and impaired breathing that leads to death, memory impairments, and paranoia.
This anti-depressant is also used to treat insomnia.
Black Box Warnings
In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses
This increase was not seen in patients >24 years; a slight decrease in suicidal thinking was seen in adults >65 years
In children and young adults, risks must be weighed against the benefits of taking antidepressants
Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments
The patient’s family should communicate any abrupt changes in behavior to the healthcare provider
Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy
This drug is not approved for use in pediatric patients
Adverse effects include paresthesia, tachycardia, confusion, weakness, and other serious and non-serious risks.
Melatonin Receptor Agonist
This prescription sleep aid is designed to assist with a form of insomnia, a non-24-hour sleep/wake cycle, that affects people who are totally blind. The cost is over $15,000 for a 30-day supply and may take weeks or months to be effective.
It’s limited use and status as an orphan drug means it is not a good candidate for the best insomnia prescription sleep aid for sighted people.
Like other insomnia treatments, Ramelteon may impair the ability to function or perform hazardous tasks the next day.
While there is a potential for cognitive and behavioral changes, the reported adverse effects are not as numerous or life-threatening as many other insomnia treatments.
Adverse Effects include dizziness, headaches, fatigue, nausea, depression, and hallucinations – all common side affects of prescription sleep aids.
At a cost of $82 for a month’s supply, Ramelteon appears to be the best prescription sleep aid due to fewer potential adverse effects and a price that is affordable for many people.
Serotonin Antagonist and Reuptake Inhibitor
Trazodone is primarily an anti-depressant that is used off label for insomnia.
Black Box Warnings
In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses.
Behavioral changes, including prolonged or inappropriate erections, increased bleeding, and suicidal ideation are a significant concern when taking Trazodone. There is a 5 – 40% risk of blurred vision, dizziness, and milder physical symptoms.
Additional side-affects, some of them serious, were reported with low frequency.
Selective, Dual Orexin Receptor Antagonist
In clinical trials, the adverse effects were not serious but after being used by the public, cardiac disorders, tachycardia, heart palpitations, and nervous system disorders were reported.
Additional Life-Threatening Risks of Prescription Sleep Aids
Prescription sleep aids should not be used for long-term relief of sleep problems. Regardless of which type you are prescribed; they provide only a dose-dependent temporary solution that carries substantial risks. Researchers report shocking health risks from the use of prescribed sleeping aids that are taken as directed. These risks include:
If you take between 19 – 132 pills a year, you are 43 times more likely to die during the next 2.5 years than someone who doesn’t use any sleeping pills
If you take more than 133 pills a year (about 1 every third night), you are 5 times more likely to die during the next 2.5 years than individuals who do not take any sleeping pills
Taking sleeping pills is associated with a 35% increased risk of cancer when more than 132 pills are taken in a year and a 20% increase in the risk of cancer with 19 – 132 pills a year
No difference in the risk of death was observed between the newer versions of sleeping pills that are marketed as safer because they are faster acting. Researchers who evaluated the effect of insomnia without medication on mortality determined that it was taking sleeping pills, not the insomnia, that was responsible for reduced life expectancy.
The increased risk of accidents and falls is partially responsible for the increased risk of death. The inability to focus well enough to safely operate vehicles and machinery is also partially responsible. Failing to address underlying physical and mental health issues that are causing insomnia also contributes to the increased risk of premature death.
Alternatives to Sleeping Pills
Prescription sleep aids are not recommended as a long-term solution for sleep problems. The official recommendation is to look for a primary psychiatric disorder or underlying medical illness if insomnia is not eliminated in 7 – 10 days of treatment with a prescription sleep aid. They also should not be the first line of defense. Health care providers are advised to carefully evaluate patients for underlying physical or mental issues prior to prescribing a sleep aid.
Individuals with a healthy mind and body will be able to sleep naturally. Insomnia is a symptom of something else. In many cases, anxiety and depression are the underlying cause. Sometimes the cause has a physical basis.
One form of Cognitive Behavior Therapy (iCBT) is very effective on insomnia with benefits seen in as little as one session and complete remission of insomnia symptoms following six sessions. Although the cost of therapy is initially more than the cost of a prescription, across time, the cost is significantly lower from the perspective of dollars spent as well as wear and tear on the mind and body.
Stress Management Skills Development
Most insomnia, including the inability to get to sleep and back to sleep after waking, is related to stress and anxiety. When the mind repeatedly brings up troublesome thoughts, relaxing into sleep becomes difficult.
Learning and using stress management skills develops the ability to take control of your runaway thoughts and calm your mind so worries, guilt, grief, and anxiety doesn’t keep you awake. These skills can be developed with the assistance of a mental health professional or using self-help methods including books that teach you how to develop healthier habits of thought.
There are three primary pillars of health: good nutrition, adequate sleep, and exercise. Of the three, sleep is the most important because lack of sleep can cause death in a short period of time, directly, or by causing a fatal accident. In as little as three or four days, lack of sleep causes hallucinations. There are no human reports of dying from lack of sleep since such experiments would violate ethical standards, however, there are animal tests where all the animals died when they were completely deprived of sleep.
Insomnia puts individuals between a rock and a hard place. They need to sleep but the risks of most prescription sleep aids can be significant for healthy individuals and even worse for the elderly and people with pre-existing illnesses or a history of drug dependence.
Best Prescription Sleep Aid
Your physician will evaluate your medical history, pregnancy and nursing status, age, and any issues with drug or alcohol dependence before making a decision on what to prescribe. Your doctor will also evaluate other drugs you may be taking for drug interactions.
If your doctor prescribes Ramelteon (Rozerem), you will be taking the prescription sleep aid with the lowest risk of adverse side effects.
Regardless of what your physician prescribes, remember that sleeping pills are not a cure for insomnia – they are only a dose-dependent way to get some sleep on a temporary basis. The risks associated with long-term use are high. There are other methods of addressing insomnia that do not require you to take dangerous prescription sleep aids.