FRENY MENEZES
By Freny Menezes

Pharm. D

03 October 2022
Medically reviewed by
Kajal Jain
M. Pharm
Ambien-vs-Melatonin
Table of Contents

Sleep is essential in allowing our body to rest and regenerate. When sleep quality is compromised beyond feeling sleepy and grumpy, additional health impacts may result from ongoing disruptive sleep. These impacts include an increased risk of vascular disorder, metabolic dysfunction, high blood pressure, cardiovascular disease, and neurocognitive disorders.

With aging comes changes in sleep-wake cycles that increase the likelihood of insomnia. The elderly are especially susceptible to insomnia. In contrast to the 10-15% prevalence of sleep issues among 18 to 35-year-olds, this number climbs to 30% among individuals over the age of 65.

So, to maximize sleep quality when one experiences insomnia or poor sleeping patterns, either lifestyle changes or prefers sleep aids. But do they resolve the issue? We are here to explore the dissimilarities of two sleep aids, i.e., Ambien and Melatonin.

What is Ambien?

Ambien (Zolpidem) slows down the activity in the brain, allowing you to fall asleep. Its immediate-release formulation dissolves right away, helping you fall asleep fast. The extended-release form has two benefits, i.e., it helps you to fall and stay asleep. Zolpidem offers several benefits, including:

  • It shows its effect quickly, generally within 30 minutes.
  • Zolpidem helps initiate the sleep process.
  • Sleep disorders often improve within 7 to 10 days from the start of medication.

Used correctly, zolpidem may be a great option if you need a short-term medication to help you overcome a temporary bout of insomnia.

How Does Ambien Work?

An imidazopyridine with a brief hypnotic effect, zolpidem is beneficial for treating insomnia. It is a positive allosteric modulator of the gamma-aminobutyric acid (GABA) type A receptor complex. 

Zolpidem binds to the alpha-1 subunit of the gamma-aminobutyric acid-A receptor, which decreases neuronal activity in a variety of brain regions and is present in regions of the brain that control sleep/wakefulness and sedation.

What is Melatonin?

The pineal gland naturally secretes Melatonin hormone in the brain. It regulates other hormones and maintains the body's circadian rhythm (internal 24-hour "clock"), which helps in falling asleep and waking up.

Melatonin production decreases during day time and vice-versa when it gets dark. Melatonin is not a vitamin but a natural hormone produced in the body (the endogenous hormone). Melatonin supplements (exogenous hormone) are produced synthetically, and all products and strengths are available without a prescription in the U.S. market in nutrition stores, pharmacies, and other retail shops.

Some people who find difficulty in sleeping have lower levels of Melatonin. Melatonin supplements might help them in getting better sleep.

Melatonin was discovered in 1958 and is sold as an OTC drug in Canada and the United States. While it is a prescription-only medication in the United Kingdom. It is not approved by the US Food and Drug Administration (FDA) for medical use.

People commonly use Melatonin to treat insomnia and improve the sleep cycle in conditions like jet lag. It is also used for chronic pain, depression, dementia, and others.

Scientists are also looking at other benefits, such as whether it might be used to

  • Prevent or minimize the problems with sleeping and confusion after surgery.
  • Treat Seasonal Affective Disorder (SAD).
  • Reduce long-term cluster headaches.
  • Regulate sleep patterns for people working night shifts.
  • If you are considering using Melatonin supplements, talk to your doctor first.

The pineal gland naturally secretes Melatonin hormone in the brain. It regulates other hormones and maintains the body's circadian rhythm (internal 24-hour "clock"), which helps in falling asleep and waking up.

Melatonin production decreases during day time and vice-versa when it gets dark. Melatonin is not a vitamin but a natural hormone produced in the body (the endogenous hormone). Melatonin supplements (exogenous hormone) are produced synthetically, and all products and strengths are available without a prescription in the U.S. market in nutrition stores, pharmacies, and other retail shops.

Some people who find difficulty in sleeping have lower levels of Melatonin. Melatonin supplements might help them in getting better sleep.

How Does Melatonin work?

Melatonin promotes sleep in humans and plays a part in controlling the sleep-wake cycle. Melatonin regulates circadian rhythms and soporific activity through its own receptors (MT1, MT2), which are G protein-linked receptor family members. 

Melatonin acts on the receptors to cause physiological changes, such as decreasing body temperature and respiration rate, that put your body in a calmer, drowsy condition to encourage sleep.

Comparative Assessment Of Melatonin Vs Ambien

 Generic Name

Ambien

Melatonin

Brand Name

Zolpidem

Melatonin

Drug class

Sedative/hypnotic

Antidepressant

First Approval

December 16, 1992

Not approved

FDA Approved indications

Short-term treatment of insomnia, generally for sleep-onset insomnia

Not FDA approved

Dosage

Recommended daily dose is 5mg or 10mg at bedtime

Recommended daily dose is 0.125mg, 0.3mg, 0.5mg, 2mg CR, 3mg, 5mg, 10-50mg at bedtime

Dosage Form

They are produced as oral tablets. Sublingual tablets or oral spray

Available as oral tablets

Oral bioavailability

70%

15%

Elimination half-life

2.6 hrs

Drug elimination through kidney and feces

20-50 min

Contraindications

Hypersensitivity to zolpidem tartrate

Hypersensitivity

Dosing Information

Choosing the appropriate dosage regimen is important for attaining the intended therapeutic efficacy and preventing adverse effects. A drug may produce different pharmacological responses at the same dose, which is typically attributed to inter-subject variability. 

For various reasons, many patients do not take their prescriptions as prescribed by their doctors. For example, failing to comprehend the instructions, forgetting, taking various prescriptions with different regimens, experiencing unpleasant side effects, or the medication not appearing to be functioning.

Medication adherence is critical to managing chronic conditions, treating temporary conditions, and maintaining long-term health.

Ambien

Melatonin

Immediate-release tablets: The recommended dose is 5 mg in women and either 5 or 10 mg in men before bedtime

Extended-release tablets: The usual dose is 6.25 mg in women and 5.25 mg or 12.5 mg in men.

The usual dose is between 1-5 mg before bedtime.

Primary sleep disorders: 0.1 mg to 0.5 mg 30 minutes before bedtime

Difficulty falling asleep: The dose is 5 mg orally 3-4 hours before sleep for 4 weeks.

For jet lag: 0.5-5 mg orally at bedtime

Take Ambien before bedtime with 7- 8 hours intervals before waking up.

The tablets should be taken 1-2 hours before bedtime and after food. 

Side Effects

Ambien and Melatonin also come with their share of potential side effects. While many are relatively common and harmless, others can be dangerous. In case of any side effects are observed, they should be informed to the doctor after being noticed.

Melatonin's Common Side Effects Ambien Common Side Effects
Dizziness, fatigue Loss of coordination
Abdominal cramps Ataxia
Decreased alertness  Daytime drowsiness, dizziness, lightheadedness
Disruption of circadian rhythm Weakness, fatigue
Depression (temporary) Nasal irritation, stuffy nose
Drowsiness Dry mouth
Irritability Nausea
Headache Constipation, diarrhea
 

 

 

Tell your doctor if you have uncertain but severe side effects of Ambien, including Behavioral changes (such as depression, abnormal thoughts, suicidal thoughts, confusion, hallucinations, agitation, aggressive behavior, or anxiety).

Interactions of Melatonin and Ambien

Ambien is a sedative/hypnotic drug that might interact with other sedative medications or slow your breathing (viz., pain medications, muscle relaxants, cold medicines, and medicines for anxiety, depression, or seizures) or antidepressant drugs.

Ambien may also interact with alcohol or drugs that increase the side effects or worsen the existing ones, such as rifampin, ketoconazole, itraconazole, or chlorpromazine.

If your medical practitioner has recommended using these medicines, he might already be aware of any possible drug interactions. Do not start, discontinue, or alter the dosage of any drug before checking with your doctor or pharmacist first.

Melatonin has moderate interaction with at least 222 different drugs. Its serious interaction is with sodium oxybate. It also interacts with benzodiazepines, contraceptives, antipsychotic drugs, HIV medicines, some antidepressants, digoxin, NSAIDs, blood thinners, MAO inhibitors, diuretics, St. John's wort, tramadol, medicines to treat mental illness, tamoxifen, alcohol and migraine headache medicines.

Is Melatonin or Ambien better?

As per the National Institutes of Health, more than one-third of Americans suffer from sleep deprivation. Sleep medication may seem like a lifesaver. And used sparingly, it may help you get the sleep you need.

However, long-term use is not recommended for most sleep aids. Many sleep aids are available, and your healthcare provider may determine the underlying condition of your sleep disruption, such as sleep apnea or restless leg syndrome.

They can also help you develop a treatment plan and make sure you are using sleeping aids correctly. Ambien (zolpidem) and Melatonin are used to treat insomnia.

However, Melatonin is primarily used to treat depression. Both drugs belong to different drug classes. Melatonin is an antidepressant, whereas Ambien is a sedative/hypnotic drug.

Both drugs are well-tolerated. Melatonin demonstrated no major difference in patient-perceived sleep effectiveness, disturbance, supplementation, or adverse effects compared to zolpidem. However, Melatonin might be a more favourable option as it is not associated with serious side effects.

The results of the Stoianovici study showed that melatonin and zolpidem had identical effects on patient-perceived sleep. When compared to zolpidem, melatonin likewise did not demonstrate any differences in sleep disturbance or supplementation.

Both melatonin and zolpidem were well tolerated, with the only noticeable side effects being drowsiness and headache. Despite the fact that both treatments were equally effective in promoting sleep, using melatonin may be preferable because it has fewer potentially harmful side effects. 

Precautions

A precaution is a cautionary step you take to make sure the drug is safe. It is taken before the administration of a drug to avoid anything unfavorable or harmful happening.
Precautions you should follow before taking Ambien (zolpidem)-
1. Inform your doctor if you are allergic to zolpidem.
2. Inform your doctor if you have:

  • liver or kidney disease;
  • depression;
  • mental illness;
  • suicidal thoughts;
  • drug or alcohol addiction;
  • lung disease or breathing issues.

3. Avoid activities requiring mental aleetness such as driving or operating heavy machinery after taking Ambien.

4. Ensure you have 7-8 hours of sleep after taking Ambien.

5. Ambien use during the last three months of pregnancy may cause drowsiness or breathing issues in the baby.

6. While taking this medication, breastfeeding might not be safe. Inquire with your doctor about potential risks.

Precautions you should follow before taking Melatonin- 

-Melatonin may make a person drowsy; if this happens, the patient should avoid driving or engaging in other risky activities that put them or others in danger.

-Melatonin usage is not advised for people who have autoimmune illnesses or are using immunosuppressants.

- Melatonin may, in rare circumstances, make restless legs syndrome worse.

-If in doubt, consult your doctor before combining this medication with any other prescription medications, OTC products, or dietary supplements.

-Avoid alcohol intake when on melatonin.

-Avoid caffeine-containing products like coffee, tea, cola, energy drinks, and other things because they can negate the benefits of melatonin.

-Pregnancy - Use in expectant mothers and women planning pregnancies is not advised.

-Breastfeeding is not advised for women who are using melatonin supplements. Human breast milk contains endogenous melatonin, suggesting that exogenous melatonin is likely released into human milk.

Interactions of Melatonin and Ambien

Inform your doctor and pharmacist about any additional medications you are taking before beginning any new course of treatment. Giving them this information could prevent any potential interactions.

Interactions of Ambien

-Ambien is a sedative/hypnotic drug that might interact with other sedative medications or slow your breathing (viz., pain medications, muscle relaxants, cold medicines, and medicines for anxiety, depression, or seizures) or antidepressant drugs.

-Ambien may also interact with alcohol or drugs that increase the side effects or worsen the existing ones, such as rifampin, ketoconazole, itraconazole, or chlorpromazine.

-Coadministration of zolpidem with alcohol and other CNS depressants increases the risk of CNS depression.

-Using opioids concurrently raises the possibility of respiratory depression.
- Imipramine and Ambien together reduce alertness.

- Use of zolpidem in combination with chlorpromazine may reduce alertness and psychomotor function.

-Combining St. John's wort with zolpidem may result in lower zolpidem blood levels.

-Giving zolpidem and sertraline at the same time enhances zolpidem exposure.

-CYP3A4 inducers (such as rifampin or St. John's wort): Combining these medications may lessen their effects.

Interactions of Melatonin

- Its serious interaction is with sodium oxybate. 

-Melatonin use in combination with anticoagulants, antiplatelet medications, herbal supplements, and other medications may raise the risk of bleeding.

-Melatonin may counteract the effects of anticonvulsants in children with neurological impairments.

- In persons taking blood pressure drugs, melatonin may make their blood pressure worse.

-CNS depressants- The use of melatonin along with these drugs may have an added sedative effect.

- Antidiabetic medications- Sugar levels may be impacted by melatonin. Melatonin should be used with caution if you use diabetes drugs.

-The effects and potential side effects of melatonin may be increased when it is combined with contraceptive medication.

-It also interacts with HIV medicines,benzodiazepines, digoxin, NSAIDs, MAO inhibitors, tramadol, tamoxifen, alcohol and migraine headache medicines.

Bottom Line From Practical Anxiety Solutions

The habit-forming nature and detailed list of potential adverse effects associated with sleeping pills make this approach a higher risk and do not address the cause of poor sleep. Then again, Melatonin seems, by all accounts, to be more moderate and safe when compared to other sleep aids.

Both drugs are well-tolerated. Melatonin demonstrated no major difference in patient-perceived sleep effectiveness, disturbance, supplementation, or adverse effects compared to zolpidem. However, Melatonin might be a more favorable option as it is not associated with serious side effects.
In either approach, seek consultation with your healthcare professional to ensure the treatment is tailored to your needs.

Alternative methods, such as cognitive behavioral therapy and establishing a sleep routine, before exploring medications shall also be considered.

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  • An JH, Park MJ, Fava M, Mischoulon D, Kim H, Jang J, Hong JP, Park JS, Jeon HJ. Comparisons Between Successful Versus Unsuccessful Switches From Benzodiazepines or Zolpidem (Z-Drug) to Controlled-Release Melatonin in Patients With Major Depressive Disorder and Insomnia. Front Psychiatry. 2020 May 19;11:444. doi: 10.3389/fpsyt.2020.00444. PMID: 32508689; PMCID: PMC7248372. Obtain On 03/10/2022
  • www.ambien.com Obtain On 03/10/2022
  • Tan, Dun‐Xian, et al. "One molecule, many derivatives: a never‐ending interaction of melatonin with reactive oxygen and nitrogen species?." Journal of pineal research 42.1 (2007): 28-42. From https://doi.org/10.1111/j.1600-079X.2006.00407.x  Obtain On 03/10/2022

 

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