SUMAYYA
04 October 2022
Medically reviewed by
Kajal Jain
M. Pharm
ambien-vs-doxepin
Table of Contents

Nowadays, Many people have insomnia; it is widely spreading among all adults due to stress, workplace tension, health and financial issues, and poor lifestyle habits. 

About 36./. of UK adults are facing sleeping trouble during the night. There are many ways to overcome insomnia: some healthy lifestyle patterns, Meditation, following some therapies, etc. Regarding medication there,

Doxepin and zolpidem are primarily used in the market. Let us understand in detail both the drug differences, 

What Is Zolpidem?

Zolpidem (Ambien) is an effective sedative-hypnotic for the short-term treatment of insomnia. It has a rapid onset of action and a short duration of action and elimination half-life, making it useful as a sleep aid. Zolpidem is a Schedule IV controlled substance as it has the potential for abuse.

It is indicated for short-term treatment of insomnia in adults Used for neurologic conditions, migraine headaches, and to relieve stress. 

Working Mechanism

Zolpidem is an imidazopyridine compound that acts as an agonist at the benzodiazepine binding site of the GABA receptor. It binds to the GABA-A-containing alpha receptors and slows brain activity, thereby inducing sleep. Zolpidem has a rapid onset of action. It reduces sleep latency and increases sleep duration.

What Is Doxepin?

Doxepin (3 mg and 6 mg), which received FDA approval in March 2010, is just the second sleep aid that is not a controlled substance. As such, it may be helpful for individuals with a history of substance dependence.

Low-dose of Doxepin—3 mg and 6 mg - is effective for insomnia characterized by frequent or early morning awakenings and an inability to fall back asleep.

Low dose doxepin- used to treat individuals with sleep maintenance insomnia, characterized by recurrent or early-morning awakenings and difficulty falling back asleep, Indicated for depression and Anxiety.

Working Mechanism

Doxepin is a tricyclic medication with cholinergic, histaminergic, and alpha1-adrenergic receptor-blocking properties. Doxepin also prevents the reuptake of serotonin and norepinephrine.

Doxepin is hypothesized to have antidepressant properties because it prevents serotonin and norepinephrine from reabsorption at synaptic clefts.

Doxepin is a histamine antagonist that works primarily at the H1 receptor. Its affinity for the H1 receptor is around 100 times greater than monoamine transporters (serotonin and norepinephrine).

Activation of the H1 receptor is crucial in mediating arousal, and brain histamine are critical in sustaining awake. The blockade of the H1 receptor by Doxepin most likely contributes to the decline in wakefulness.

Dosage Of Zolpidem And Doxepin

Zolpidem

It is available in:

  • Zolpidem (5- and 10-mg tablets),
  • Oral spray - Zolpidem 5 mg/spray
  • Ambien (5- and 10-mg tablets),
  • Ambien CR (6.25- and 12.5-mg tablets).
  • Use the lowest effective dose.
  • Take one dose before bedtime with 7-8 hours of sleep before waking.

Doxepin

Doxepin has long been available in

  • Doxepin capsules to treat depression and Anxiety – available in 10, 25, 50, 75, 100, and 150 mg
  • Topical preparation (5% cream) for pruritus, but not in dosages <10 mg.
  • A generic doxepin oral solution (10 mg/ml) is available and can be titrated to smaller dosages by a dropper.

Dosing For Insomnia

  • In adults, the recommended hypnotic dose for Doxepin is 6 mg 30 minutes before bedtime.
  • For patients more than 65 years, the recommended starting hypnotic dose is 3 mg 30 minutes before bedtime, increased to 6 mg if indicated.

Dosing For Depression/ Anxiety

  • Start with a low dose of 25mg/ day; gradually titrate upward every 5 to 7 days.
  • For geriatric patients, start with 10mg/ day and adjust the dose gradually; the Dosing range is 10-25 mg PO before bedtime.

Possible Side Effects

Zolpidem Doxepin
Rapid or irregular heartbeat Agitation
Nausea and vomiting Blurred vision
Abdominal pain Constipation
Diarrhea Dizziness
Appetite loss Drowsiness
Double vision Dry mouth
Respiratory depression Fatigue
Muscle cramps Nausea and vomiting
Skin rashes Weakness
Abnormal body movements Headache
Confusion Confusion
Loss of memory Seizures
Hallucinations Sweating
Depression Sexual dysfunction

While not significantly affecting sleep onset, Doxepin 3 mg and 6 mg enhances and sustains sleep maintenance and sleep duration into the final quarter of the night. Zolpidem increases total sleep time and sleep efficiency and decreases sleep latency. With Doxepin, next-day side effects do not occur. The most common side effects are headache and sleepiness/sedation.

Case studies have documented sleepwalking, sleep eating, sleep conversations, sleep driving, and sleep sex in adults. These behaviors are uncommon and occur in patients taking high doses of zolpidem who have underlying psychiatric disorders, medical conditions, or drug-drug interactions.

In elderly individuals, Doxepin seems to be well tolerated. Zolpidem has the danger of dependence. The usage of zolpidem decreases performance in elderly subjects. When it comes to lowering sleep onset latency, zolpidem outperforms Doxepin.

Doxepin Vs Ambien: Which Is More Effective?

While not significantly affecting sleep onset, Doxepin 3 mg and 6 mg enhances and sustains sleep maintenance and sleep duration into the final quarter of the night. Zolpidem increases total sleep time and sleep efficiency and decreases sleep latency. With Doxepin, next-day side effects do not occur. The most common side effects are headache and sleepiness/sedation.

Case studies have documented sleepwalking, sleep eating, sleep conversations, sleep driving, and sleep sex in adults. These behaviors are uncommon and occur in patients taking high doses of zolpidem who have underlying psychiatric disorders, medical conditions, or drug-drug interactions.

In elderly individuals, Doxepin seems to be well tolerated. Zolpidem has the danger of dependence. The usage of zolpidem decreases performance in elderly subjects. When it comes to lowering sleep onset latency, zolpidem outperforms Doxepin. 

Studies Related To Doxepin And Ambien Use In Sleep-related Disorders

A comparison between Doxepin, benzodiazepines, and nonbenzodiazepines suggests that Doxepin may be better than nonbenzodiazepines at improving sleep duration and maintenance. Doxepin is less effective than nonbenzodiazepines and benzodiazepines in lowering sleep onset latency.

In a 2008 trial, Scharf et al. investigated the Safety and effectiveness of 1, 3, and 6 mg of Doxepin in patients above the age of 65 years. A placebo or Doxepin was given randomly to 76 persons with primary insomnia for two nights. Patients who took any dose of Doxepin experienced objective and subjective improvements in sleep duration and maintenance of sleep, which lasted into the final hours of the night. At all three doses, there was an improvement in both total sleep time and sleep efficiency.

In a study by Krystal AD, side effects included nausea (4–5%), somnolence (8–9%), and dizziness (2%). There were no reports of complex sleep behaviors, memory impairment, or cognitive disorders in the doxepin-treated elderly patients.

In a different study by Scharf, 768 older insomniacs participated in a two-phase trial. The usual treatment was compared to 4 weeks of zolpidem (5 or 10 mg).

Using immediate zolpidem release (IR) at both 5 and 10 mg, subjective sleep onset latency, average time awake at night, and the number of awakenings (NOA) decreased while total sleep time (TST) increased.

Precautions That Need To Be Taken

Why Are Precautions Needed?

Precaution is needed in consuming drugs while taking it states some information about the drug; every individual should know and be aware of the drug precautions. They can consult their doctor and also read the label given below the tablets. 

Doxepin Precautions:

  • Before consuming the drug, inform your doctor if you have any allergic reactions to some of the anti-depression because they may have some inactive ingredients, which will cause rashes and swelling in the skin.
  • Inform your doctor if you have any history of heart problems, liver problems, or other mental issues.
  • Doxepin makes you feel dizzy and drowsy so avoid drinking alcohol while taking the drug.
  • Do not drive or do not do any activity after taking the drug 
  • Older adults should take the medication in a limited amount of  dosage because, in older adults, it will make them symptoms of dry mouth, feelings of dizziness, rough confusion
  • While consuming this drug, if you face any unusual things in your behavior or trouble with your child as a symptom, you should inform your doctor immediately 
  • Tell a doctor if you have any feelings of nervousness, restlessness, or scared because it may develop the bipolar disorder 
  • Inform your doctor if you are pregnant or planning to become pregnant. This medication will cause breathing problems.

Zolpidem Precautions 

  • Using this medication during pregnancy will cause danger to the Unborn baby, so check with your doctor about your pregnancy.
  • Discuss it with your doctor if you have been using Ambien for more than 7 to 10 days.
  • It may cause severe allergic reactions and lead to life-threatening conditions. You face trouble breathing or swallowing, so inform your doctor immediately.
  • This medicine will help you sleep and not be able to remember the following day, so avoid car driving or any activity.
  • This medication causes older persons to become more Drowsy, light-headed, clumsy, and unsteady, so older people should use only the lesser dosage. 
  • Do not change your dose or stop suddenly unless your doctor consents because you will develop withdrawal symptoms and may face side effects like vomiting, seizure, nausea, and nervousness.

Drug interactions

Why should people know about drug interactions?

Drug interaction will help you know which drugs should be taken together and not so well in practice or the medication. Read out the label and follow the instructions.

Drug interaction of Doxepin

  Avoid taking MAO inhibitors like

  • Isocarboxazid
  • Linezolid
  • Metaxalone
  • Phenelzine
  • Procarbazine

with Doxepin because it may lead to severe effects of drug interactions. Some drugs, like cimetidine and terbinafine, will make the doxepin work less effectively. Inform your doctor if you are using products that cause drowsiness, like opioid pain, cough relievers, or alcohol.

Drug interaction of zolpidem

Selective serotonin reuptake inhibitors:

Ambien can interact with the SSRIs group of drugs but will increase the risk of Ambien causing side effects.

Benzodiazepines:

While interacting with Ambien. You may have a higher risk of side effects from both the group of drugs; if you take Ambien and benzodiazepine, it can increase the CNS side effects and show some symptoms.

Interacting with herbs and supplements

Before interacting with certain herbs and supplements, you should consult a doctor.

Avoid interacting with alcohol. It will lead to severe drowsiness and worsen your condition

Bottom Line From Practical Anxiety Solutions

Doxepin could be considered as first-line therapy for adults and older people with sleep maintenance insomnia. Zolpidem is more effective than Doxepin in reducing sleep onset latency.

Furthermore, ultra-low-dose Doxepin has not been shown to cause physical dependence or tolerance or to be related to abuse potential, making it a possible alternative for those with a history of these problems.

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