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Doxylamine Succinate vs Diphenhydramine HCL

Difference between doxylamine succinate and diphenhydramine HCl?


Insomnia is a condition that is characterized by having trouble staying asleep or falling asleep, waking too early, and feeling unrested.

It’s estimated that over 70 million people in the United States have trouble sleeping and, with the proliferation of bad habits and gadgets, the problem is progressively getting worse.

Here is a comparison between doxylamine succinate and diphenhydramine, two antihistamines that some people use to fall asleep:

Doxylamine Succinate

Due to its sedative effects, doxylamine is used as a short-term treatment for insomnia.

Doxylamine belongs to a family of drugs called sedating antihistamines.

It is found in over-the-counter products such as Nyquil and Unisom.


This drug belongs to a family of drugs called antihistamines which many people use as a sleep aid.


Doxylamine is used in the short-term treatment of insomnia.

Also, it is used in combination with decongestants to relieve a runny nose, sneezing, and nasal congestion caused by allergies or the common cold.

Diphenhydramine is mainly used as a cough suppressant in cough mixtures and as an aid to induce sleep.

Mechanism of Action

Doxylamine succinate works by blocking the effects of histamine, a chemical occurring naturally in the human body.

Diphenhydramine works by reducing the effects of histamine in the body.

Side Effects

Doxylamine is generally safe, however, it can cause side effects that are typically minor but occasionally serious, including:

  • difficulty urinating;
  • drowsiness;
  • irregular heart rate;
  • dizziness;
  • excessive sweating;
  • loss of coordination;
  • abnormal heart rhythms;
  • headache;
  • sensitivity to light;
  • stomach pain;
  • seizures;
  • thick lung secretions;
  • acute labyrinthitis;
  • dry mouth or nose;
  • low blood cell counts;
  • hyperactivity;
  • erectile dysfunction;
  • double vision;
  • low blood pressure;
  • constipation;
  • severe allergic reactions, including difficulty breathing.

Note – this antihistamine causes drowsiness, which is considered a side effect when used for other purposes but a beneficial effect when used as a sleep aid.

Possible side effects of diphenhydramine include:

  • loss of coordination;
  • fluttering in your chest;
  • drowsiness;
  • pounding heartbeats;
  • dizziness;
  • difficult urination;
  • dry mouth, nose, or throat;
  • little urinating;
  • blurred vision;
  • dry eyes;
  • confusion;
  • day-time drowsiness;
  • upset stomach;
  • uncontrollable movements of your tongue;
  • constipation;
  • tightness in your jaw or neck.


The usual recommended dose for doxylamine succinate is 25 mg orally once per day, 30 minutes before bedtime.

Important note – do not take this antihistamine more than 14 days consecutively.

The usual recommended dose for Diphenhydramine is 25 to 50 mg orally at bedtime.

Warnings & Precautions


Do not use this antihistamine:

  • if you have difficulty passing urine;
  • if you have asthma;
  • if you have epilepsy;
  • if you have chronic bronchitis;
  • if you have a narrowing or blockage between the small intestine and stomach and that causes vomiting of undigested food;
  • if you have severe kidney disease;
  • if you have severe liver disease;
  • if you are allergic to this antihistamine;
  • if you have unusual heartbeats;
  • if you are taking medicines to help you relax or sleep, tricyclic antidepressants, or strong painkillers;
  • if you have increased pressure in the eye;
  • if you are a man with prostate problems.

Other precautions include:

  • this antihistamine can decrease sweating and may make you more prone to heatstroke;
  • due to the fact that it can cause blurred vision, it is recommended to be careful while driving or doing anything that needs you to be alert while using this medication;
  • it is not recommended for use in children under 12 years of age.


Ask a healthcare provider if it is safe for you to take this antihistamine if you have:

  • an enlarged prostate;
  • an eye disorder that results in optic nerve damage;
  • heart disease;
  • chronic bronchitis;
  • a thyroid disorder;
  • emphysema;
  • low blood pressure;
  • abdominal surgical procedures;
  • urinary problems;
  • bowel obstructions;
  • stomach ulcer;
  • chronic breathing disorders;
  • liver impairment.

Drug Interactionsdrugs

Doxylamine may interact in a negative way with the following medications:

  • Ambien (zolpidem);
  • paroxetine;
  • Benadryl;
  • tramadol (an opioid pain medication);
  • codeine;
  • zolpidem;
  • Cymbalta (duloxetine);
  • Zyrtec (cetirizine);
  • dextromethorphan);
  • Zoloft (sertraline);
  • Lexapro (escitalopram);
  • Xanax (alprazolam);
  • sertraline (an antidepressant of the selective serotonin reuptake inhibitor class);
  • mirtazapine;
  • Lyrica (pregabalin).

Diphenhydramine may interact in a negative way with the following medications:

  • dextromethorphan;
  • Ambien (zolpidem);
  • Norco (an opioid pain reliever);
  • BuSpar (buspirone);
  • Vicodin (a powerful painkiller);
  • Xanax (alprazolam);
  • cetirizine;
  • mupirocin;
  • Zyrtec (cetirizine);
  • Cymbalta (duloxetine);
  • Zoloft (sertraline);
  • hydrocodone;
  • tramadol;
  • Lyrica (pregabalin);
  • Lexapro (used to treat depression and anxiety).

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Do not drink alcoholic beverages while taking these sedating antihistamines.

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Is It Safe During Pregnancy or Breastfeeding?pregnant woman

If you are pregnant or breastfeeding, first consult with your healthcare professional about whether you can use these sedating antihistamines, as they could cause harm.

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Doxylamine Succinate vs Diphenhydramine HCL – Differences

Doxylamine succinate is an antihistamine that works centrally within the brain, where it causes sedation.

Diphenhydramine is also a sedating antihistamine that is used to induce sleep, to treat motion sickness, and to treat some symptoms of Parkinson’s disease. Also, this antihistamine is used to treat a runny nose, watery eyes, sneezing, itching, hives, skin rash, and other allergy symptoms.

Both drugs can help to induce sleep, but research has established that doxylamine succinate is the strongest sedative antihistamine.

However, both drugs share similar adverse effects (especially in seniors), like:

  • rapid heart rate;
  • inability to empty the bladder completely;
  • impaired sweating;
  • nausea;
  • constipation;
  • blurred vision;
  • dry mouth;
  • hallucinations;
  • confusion.

Therefore, it is important to talk to a doctor before taking either drug.

If you’re struggling with chronic insomnia, it is recommended to not rely on OTC sleep aids for a good night’s sleep, but start with lifestyle changes, such as:drinking coffee

  • eat light meals in the evening – eating just prior to going to bed can disrupt your sleep;
  • avoid alcohol before bedtime – alcohol is not a sleeping aid even it might seem to make you sleepy, instead, alcohol may suppress the REM sleep state which is vital to a good night’s sleep;
  • reduce your caffeine intake – as any coffee lover knows, caffeine is a central nervous system stimulant that can keep you awake. According to research in Sleep Medicine, this stimulant may impair sleep more as you get older. Keep in mind that colas, cocoa, and chocolates are sources of caffeine;
  • don’t smoke tobacco – heavy smokers wake up more frequently, they take longer to fall asleep, and they commonly have more disrupted sleep since nicotine is a stimulant;
  • don’t take naps since daytime naps may disrupt your nighttime sleep cycle:
  • if you’re unable to fall asleep after half an hour, leave the bed and do something relaxing; return to bed later;
  • exercise regularly – moderate physical exercise (like – running, swimming, walking, or cycling) can help relieve some of the tension built up over the day. A good goal is to work up to at least 60 minutes of physical exercise to prepare you for a good night’s rest. However, avoid strenuous exercise about 1 hour before bedtime as it might overstimulate you;
  • do not take unnecessary drugs as a side effect of certain drugs is insomnia, especially drugs which as are used to treat ADHD, corticosteroids, antidepressants, and anticonvulsants;
  • avoid TVs, laptops, and smartphones 2 hours before going to bed as their blue light reduces the body’s production of melatonin, a sleep-inducing hormone;
  • drink herbal teas, like – catnip, chamomile, fennel, or anise. All these teas contain natural ingredients that will help you to sleep faster;
  • go to bed at the same time each night and wake up at the same time each morning, even on holidays or weekends:
  • do relaxation exercises before going to bed, like – mindful meditation or breathing.