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Trazodone vs Ambien vs Xanax vs Seroquel vs Zoloft

During the past year, 117,291,026 prescriptions for these five sleeping pills, antidepressants, and antipsychotic drugs were written. Researchers estimate that almost 17% of Americans take at least one psychiatric drug at some time during the year.

When a drug is used off label, it means that clinical research demonstrating that its risks outweigh its benefits for that purpose doesn’t exist or hasn’t been approved by the Food and Drug Administration. Off label use of dangerous drugs is common for the treatment of insomnia even though these drugs come with the potential for serious adverse consequences.

Off label drugs are frequently prescribed to treat insomnia with little to no clinical evidence that they are effective or that their benefits outweigh the risks. In addition, these drugs are taken long-term by 80% of the patients despite expert recommendations that they should only be used on a short-term basis.

When it comes to insomnia treatments, the recommendation is to use these types of drugs about 7 – 10 days and seek other treatments to improve insomnia that persists. Cognitive Behavioral Therapy is highly effective for insomnia and improvements in sleep hygiene can make a significant difference in the ability to sleep.

Long-term use raises concerns about dependency and increases the risk of dangerous and fatal side effects. Here’s what the experts are saying:

“It would be hard to identify another class of drugs that, despite decades of use, has more questions about the patient groups for which its benefits outweigh its risks, and the incidence of severe adverse effects.”

“Antipsychotic drugs often do not provide enough benefit to justify their toxic side effects, according to a new analysis of key scientific studies published in the medical journal Drug Safety.”

Let’s look at the risks and uses of Trazodone, Ambien, Xanax, Seroquel, and Zoloft.

Trazodone vs Ambien vs Xanax vs Seroquel vs Zoloft

All of these drugs have dangerous side effects and in clinical trials, the improvements in sleep quality provided may not be worth those risks.

The common side effects of Trazodone are as bad and maybe worse than the effects of sleeping poorly. They include drowsiness, dizziness, nausea, vomiting, and blurred vision. Up to 10% of patients experience more serious side effects including blood pressure issues, confusion, and sexual problems.

The risks associated with taking Ambien are even worse and include developing dependence, loss of control of behavior, suicidal thoughts, and sleep behaviors that can lead to serious injury or death. The common side effects leave you in about the same situation you’d be in with inadequate sleep. The high prevalence of emergency department visits associated with Ambien are enough to make you pause before popping an Ambien.

Xanax comes with the risk of a higher number of serious adverse side effects including respiratory depression, coma, and death. When used to treat insomnia, it is not recommended for use beyond 7 – 10 days yet many patients are prescribed Xanax for longer term use. Over 20% of patients experience side effects that adversely affect the quality of life far more than being sleep deprived including cognitive disorders, memory impairments, and muscle weakness that causes slurred speech.

There’s no evidence Seroquel provides benefits that are worth the risks involved to treat insomnia. Increased risk of heart problems, including heart failure, and pneumonia that led to death increased blood pressure are high prices to pay for an insomnia treatment.

Zoloft is prescribed more than any other psychiatric drug despite being associated with an increased risk of suicide and common side effects that include diarrhea, dizziness, drowsiness, sexual problems, fatigue, and headache. Plus, some patients experience more serious side effects. Given the prevalence of prescriptions, almost 40,000 patients would experience the more serious side effects.

The side effects are enough to make you consider alternatives like Cognitive Behavioral Therapy that are effective without adverse side effects.


Drug Category:

SSRI – Serotonin Antagonist and Reuptake Inhibitor

Drug name:

Trazodone (Sold under brand name Desyrel)

Prevalence of Trazodone Use:

In 2013, a study of over 40 million people indicated that 4.16 million people in the United States took this drug and an average of 5.6 prescriptions were written per person in one year. In 2016, it was the 24th most prescribed medication in the United States; 25,300,258 prescriptions for Trazodone were written over the past year.

Purpose of Trazodone:

Trazodone is primarily an anti-depressant that is used off label for a variety of purposes including:

  • Insomnia
  • Aggressive Behavior
  • Cocaine Withdrawal
  • Alcohol Withdrawal
  • Prevention of Migraine

Trazodone works by changing chemicals in the brain.

Trazodone Half-life:

Between 10 – 12 hours.

Adverse side effects from Trazodone use:

Serious and life-threatening side effects have been reported by patients and their physicians related to Trazodone use. A Black Box Warning was mandated by the FDA after patients reported life-threatening side effects. Trazodone’s mandated Black Box Warning relates to an increased risk of suicidal thinking and behavior in children, adolescents, and young adults and warns that patients should be monitored closely for changes in behavior. In addition, there are numerous common side effects that decrease the quality of life.

Common side effects from Trazodone use include:

  • Drowsiness
  • Dizziness
  • Headache
  • Dry mouth
  • Nausea
  • Vomiting
  • Blurred vision
  • Fatigue

Side effects that occur in 1 – 10% of patients:

  • Constipation
  • Edema (swelling)
  • Orthostatic hypotension (blood pressure that drops upon standing up)
  • Syncope (fainting related to low blood pressure)
  • Tremors (shaking)
  • Nasal congestion
  • Weight change
  • Confusion
  • Disorientation
  • Lack of coordination
  • Ejaculation disorder
  • Decreased libido

Less than 1% of patients experience these side effects:

  • Acne
  • Alopecia (sudden hair loss)
  • Anemia (inadequate red blood cells in blood)
  • Anxiety
  • Diplopia (double vision)
  • Increased appetite
  • Insomnia
  • Priapism (pathologically prolonged erection)
  • Sedation (reduced state of consciousness)
  • Urinary retention
  • Vertigo (room spinning sensation)


Ambien is a Nonbenzodiazepine hypnotic that works as a sedative to cause sleepiness.

Drug Category:


Drug name:

Zolpidem tartrate

Sold under brand names that include:

  • Ambien
  • Edluar
  • Zolpimist
  • Intermezzo

Prevalence of Ambien Use:

19,102,809 prescriptions were written over the past year. A study conducted in 2013 reported that 4.86 million people took Ambien with the average patient being prescribed 5 prescriptions per year.

Purpose(s) of Ambien:

Ambien is used as a short-term solution for sleep onset and maintenance of sleep. It is also prescribed for Restless Leg Syndrome (RLS).

Use beyond 7 – 10 days for insomnia is not recommended. Address underlying causes of insomnia with sleep hygiene improvements and/or Cognitive Behavioral Therapy for insomnia which has a good record of improving sleep quality.

Zolpidem (Ambien) Half-life:

The half-life of Zolpidem is two hours.

Adverse side effects from Zolpidem (Ambien) use:

Ambien use is associated with more emergency department visits for adverse effects than any other psychoactive drug, with 25% of the visits requiring admission to the hospital. The majority of problems were associated with being prescribed and used in ways not recommended by the FDA and manufacturer.

Ambien is required to have a Black Box Warning relating to complex sleep behaviors that can be life-threatening. Patients taking Ambien have reported episodes of sleep-driving, sleep-walking, sleep-cooking, and sleep-sex that may be accompanied by amnesia. In some cases, these activities resulted in serious injuries or death. Unfortunately, the Black Box Warning doesn’t cover all the serious side effects Ambien can cause including:

  • A decreased level of consciousness
  • Dependence on the drug; this risk is higher for those with histories of drug or alcohol abuse
  • Severe reactions to the drug including allergic anaphylactic and anaphylaxis
  • Changes in behavior that can cause relationship or legal problems that may also be dangerous including decreased inhibition (much like the effect of drinking too much tequila), aggressive behavior, bizarre behavior, agitation, and depersonalization.
  • Respiratory depression and worsening respiratory disease
  • Worsening depression including suicidal thoughts and completed suicides
  • Impaired psychomotor function that interferes with driving the next day and increases the risk of falls

Common side effects include:

  • Dizziness
  • Headache
  • Drowsiness

Side effects experienced by 2% – 4% of patients:

  • Allergic reaction to the medicine
  • Constipation
  • Depression
  • Drowsiness
  • Hallucinations
  • Lightheadedness
  • Memory disorders
  • Myalgia (muscle aches and pains – can be severe)
  • Pharyngitis (irritation or pain in the throat)
  • Palpitation (heart palpitations – feeling that the heart is pounding, racing, or skipping a beat)
  • Rash (irritated or swollen skin)
  • Sinusitis (sinus irritation)
  • Visual disturbance (vision changes such as blurred vision, dry eyes, etc.)

1% or fewer of the patients reported:

  • Asthenia (muscle weakness)
  • Diarrhea
  • Dry mouth
  • Flu-like symptoms

Warnings related to Zolpidem (Ambien) use:

Do not mix with alcohol

Do not mix with other drugs, including over-the-counter and herbal insomnia treatments

Check for drug interactions with any other medications you consume

Do not take more than the prescribed dosage

Report any side effects to your physician

Do not operate machinery, including cars, as your reaction times may be slower the next day

Do not rely upon your prescribing physician to follow the manufacturer’s recommendations that are designed to keep you healthy. 68% of patients were sustained users with 229 days of prescribed drugs despite the drug being recommended for 7 – 10 days’ use. Additionally, 23% of the patients who were prescribed Zolpidem (Ambien, etc.) were also taking a drug that should not be combined with Zolpidem.


Drug Category:


Drug name:

Alprazolam, sold under the brand name Xanax.

Prevalence of Xanax Use:

27,030,725 prescriptions for Xanax were written for 5.6 million people a year, with an average of 4.9 prescriptions prescribed per person. Note that Xanax is recommended to be used for only 7 – 10 days to treat insomnia.

Wholesale cost per dose:


Purpose(s) of Xanax:

Xanax is a short-acting benzodiazepine that was developed to treat anxiety disorders, panic disorders, and is used off label to treat insomnia. Anti-anxiety drugs with a side effect of drowsiness are often used to treat insomnia because anxiety is often the cause of insomnia. In clinical studies, up to 77% of patients experience drowsiness as a side effect of taking Xanax.

Xanax Half-life:

Alprazolam has a half-life of 11.2 hours.

Adverse side effects of Xanax use:

Xanax is a benzodiazepine with a serious Black Box Warning: 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.

Side effects may be worse for senior citizens, women, and individuals with impaired liver function.

Even healthy individuals sometimes experience serious side effects when they take benzodiazepines. Patients with the following histories should not take Xanax:

  • Drug or alcohol addiction
  • Respiratory illnesses including COPD, sleep apnea, lung diseases, and other diseases that interfere with lung function
  • Decreased liver function
  • History of psychotic illness or depression

Side effects experienced by 15% of patients taking Xanax include:

  • Depression
  • Headache
  • Constipation
  • Diarrhea
  • Dry mouth

Over 20% and up to 50% of patients experience (in order of greatest prevalence):

  • Impaired coordination
  • Increased appetite
  • Fatigue
  • Memory impairment
  • Irritability
  • Decreased salivation
  • Cognitive disorders
  • Insomnia
  • Decreased appetite
  • Headache
  • Lightheadedness
  • Dysarthria (muscle weakness that causes slurred speech)
  • Diarrhea
  • Constipation
  • Nausea
  • Vomiting
  • Weight change

Side effects experienced by 10% – 20% of patients taking Xanax:

  • Nasal congestion
  • Decreased or increased libido
  • Menstrual disorder
  • Difficulty with urination

Side effects that between 5% – 10% of patients experience:

  • Tachycardia (fast heart beat)
  • Confusion
  • Insomnia
  • Nausea
  • Vomiting
  • Blurred vision
  • Nasal congestion

Between 1% – 5% of patients experience:

  • Hypotension (low blood pressure)
  • Syncope (fainting)
  • Akathisia (uncontrolled fidgeting)
  • Dizziness
  • Increased salivation
  • Nervousness
  • Tremors
  • Weight changes
  • Talkativeness
  • Incontinence

Other reported side effects include Stevens-Johnson syndrome, angioedema, peripheral edema, Hyperprolactinemia, gynecomastia, galactorrhea, Hypomania, mania, and liver enzyme elevations.

Warnings related to Xanax use:

Do not mix with alcohol or other drugs that depress CNS

Read the package insert and ask questions

Report side affects you experience to your doctor

Do not stop use without the supervision of your physician

May cause dependence

Alprazolam is a controlled substance (Schedule IV drug)

May cause Central Nervous System (CNS) depression and reduce mental and physical abilities

Operating machinery or automobiles may result in an accident due to decreased reaction times

Seroquel (Quetiapine)

Drug name:

Quetiapine is sold under the brand name Seroquel.

Drug Category:

Atypical antipsychotics

Prevalence of Seroquel (Quetiapine) use:

8,751,996 prescriptions were written for Seroquel over the past year, many of them for insomnia despite a lack of evidence to support the use of Seroquel for insomnia.

Purpose(s) of Seroquel (Quetiapine):

Seroquel was developed for use as a short-acting antipsychotic drug used to treat schizophrenia, bipolar I disorder, major depression, and generalized anxiety disorder (GAD). Seroquel is widely used off label as a sleep aid, but research shows that the benefits do not usually outweigh the side effects.

Seroquel (Quetiapine) Half-life:

The liver metabolizes quetiapine which has a half-life of six hours.

Adverse side effects associated to Seroquel (Quetiapine) use:

Experts are questioning the use of Seroquel for insomnia. The risk of serious side effects appears to outweigh the benefits of using Seroquel for the treatment of insomnia – an off label use that isn’t supported by clinical research. The evidence suggests that Seroquel is being prescribed to patients with a higher risk of metabolic cardiovascular complications and to individuals who suffer from personality or social vulnerabilities that make the use of Seroquel ill-advised.

In Australia, 20% of the deaths associated with quetiapine (Seroquel) were not prescribed to treat a diagnosed psychiatric illness. Among the elderly, antipsychotics are associated with an increased risk of falls, cognitive deterioration, and fatalities from pneumonia, hip fractures, and strokes.

Seroquel has the following Black Box Label: Not approved for dementia-related psychosis; elderly patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk of death, as shown in short-term controlled trials; deaths in these trials appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders; prescriptions should be written for smallest therapeutically effective quantity, and caregivers should monitor and report any incidence of suicidality and associated behaviors to their healthcare professionals.

Not approved for children <10 years

There are other serious side effects from Seroquel use including:

Caution should be used with patients who have cardiovascular and cerebrovascular disease. Note that 1/3 of all deaths are attributed to cardiac disease and undiagnosed cardiac problems can significantly increase the risk.

Hyperglycemia and diabetes have been associated with serious side effects including coma and death.

Seroquel increases the risk of stroke.

Clinically significant worsening of depression and suicidal thoughts can occur.

41% of patients experienced increased blood pressure.

Up to 22% of patients experienced increased triglycerides.

Up to 13% of patients experience extrapyramidal symptoms including acute dyskinesias and dystonic reactions in the muscles, parkinsonism, akinesia (voluntary movement impairments), dyskinesia (movement disorders), neuroleptic malignant syndrome (confusion, rigid muscles, variable blood pressure, fast heart rate, high fever, and sweating), and akathisia (inability to sit still). These serious side-effects of this anti-psychotic drug seriously reduce the patient’s quality of life.

Common side effects also include:

  • Constipation
  • Dizziness
  • Drowsiness
  • Dry mouth
  • Fatigue
  • Headache
  • Increased total cholesterol
  • Increased appetite

Other side effects include:

  • Abdominal pain
  • Arthralgia (joint pain)
  • Back pain
  • Blurred vision
  • Dyspepsia (indigestion)
  • Hemorrhage
  • Myalgia (muscle pain)
  • Neck pain
  • Neutropenia (low white blood count)
  • Tremors
  • Postural hypotension (low blood pressure)
  • Tachycardia (rapid heartbeat)
  • Pharyngitis (sore throat)
  • Rhinitis (ringing in the ears)
  • Rashes

Uncommon side effects include:

  • Cardiomyopathy (reduced heart function)
  • Epistaxis (bleeding from the nasal cavity)
  • Exfoliative dermatitis
  • Leukocytosis (increased white cell count)
  • Myocarditis (inflammation of the heart muscle)
  • Nightmares
  • Palpitation (racing heart)
  • Pancreatitis (inflamed pancreas)
  • Priapism (prolonged erection)
  • QTc prolongation (heart rhythm problem)
  • Rhabdomyolysis (results from muscle death and can cause kidney failure)

Warnings related to Seroquel (Quetiapine) use:

Increased risk of falls

History of Industry Misbehavior related to Seroquel (Quetiapine):

The manufacturer paid a $520,000,000 fine to settle allegations that it promoted off label use for inappropriate reasons including insomnia, anger management, and dementia and paying doctors to allow their names to be used in conjunction with ghost written articles promoting the use of Quetiapine (Seroquel).


Drug name:

Sertraline (Sold under the brand name Zoloft)

Drug Category:

SSRI antidepressant

Prevalence of Zoloft (Sertraline) use:

37,105,238 prescriptions of Zoloft were written in the past year, the most prescribed psychiatric medication in the USA, with 6.2 million people receiving an average of 5.8 prescriptions a year.

Purpose(s) of Zoloft (Sertraline):

Zoloft was developed to treat depression, OCD, panic and anxiety disorders, PTSD, and PMDD (premenstrual dysphoric disorder).

Zoloft (Sertraline) Half-life:

The half-life of Zoloft is 26 hours, which means it takes more than 5 days to metabolize out of the body.

Adverse side effects associated with Zoloft (Sertraline) use:

The FDA requires Zoloft to place a serious Black Box Warning on its label to warn patients: 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 over age 24 years; a slight decrease in suicidal thinking was seen in adults over age 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 the initial 1-2 months of therapy and following 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 for major depressive disorder, but it is approved for obsessive compulsive disorder in children >6 years

Not approved for the treatment of bipolar depression

The following side effects occur in more than 10% of patients who take Zoloft (some of these symptoms are experienced by up to 30% of patients:

  • Diarrhea
  • Dizziness
  • Drowsiness
  • Dry mouth
  • Ejaculation disorder
  • Fatigue
  • Headache
  • Insomnia
  • Nausea

Between 1% and 9% of patients experience these symptoms:

  • Agitation
  • Anorexia
  • Anxiety
  • Constipation
  • Impotence
  • Malaise (generally feeling unwell)
  • Pain
  • Paresthesia (abnormal sensations in the skin)
  • Vomiting

Uncommon symptoms include:

  • Asthenia (muscle weakness)
  • Back pain
  • Chest pain
  • Hypoesthesia (decreased sense of touch)
  • Sweating
  • Increased appetite
  • Myalgia
  • Palpitations
  • Rhinitis
  • Tinnitus
  • Weight gain
  • Yawning
  • Trismus (Lockjaw)

Warnings related to Zoloft (Sertraline) use:

Increases risk of suicidal thoughts and behavior

Abruptly stopping this drug may be dangerous – only stop with physician supervision

Read the package insert

Additional Risks of Sleeping Pills and Alternatives for Obtaining a Good Night’s Sleep

Cognitive Behavior Therapy, Stress Management skill development, and improving sleep hygiene are all more effective than sleeping pills at improving the quality of sleep.

Additional life-threatening risks are associated with the use of prescription sleep aids, including a greater risk of death from all causes.