Doxylamine Succinate vs Diphenhydramine for Sleep: Comparison of Differences & Uses

Doxylamine Succinate

It is the generic name of a brand name drug called Unisom, a first-generation antihistamine.

This medication works by reducing the effects of histamine, a natural neurotransmitter in the human body that produce symptoms of itching, runny nose, and watery eyes. In addition, this antihistamine can cause drowsiness and is occasionally used as a sleep aid.


It is used as a short-term treatment for insomnia (sleep problems). Insomnia is a condition characterized by difficulty staying asleep or falling asleep and is considered chronic if it occurs at least 3 nights per week for 90 days or longer.

An estimated 60 million people in the United States are affected by this sleep disorder every year. The causes of sleep problems can vary but they commonly include:

  • emotional stress;
  • excessive worry;
  • jet lag;
  • receiving bad news;
  • illness;
  • anxiety;
  • life circumstances;
  • pain or discomfort at night;
  • environmental factors like light, noise, or temperature;
  • shift-work;
  • physical discomfort;
  • spending too much time with the blue-tinted screens, like smartphones or tablets;
  • poor sleep hygiene practices;
  • depression;
  • intake of stimulants like – caffeine, nicotine, and alcohol;
  • using certain medicines, including some which are used to treat colds, nasal/sinus allergies, hypertension, depression, and asthma;
  • chronic stress.

This medication is also used to treat a runny nose, sneezing, hives, watery eyes, itching, skin rash, and other allergy or cold symptoms.


The usual recommended dosage for sleep problems is 25mg per day taken half an hour before bedtime. It is used in adults and children 12 years of age and older. The medication can increase the risk of falls, therefore, seniors shouldn’t use it.

If you have trouble sleeping, you should not use this medication for more than 2 weeks unless recommended by your healthcare provider.

Side Effects and Precautions

Common side effects may include:

  • mild dizziness;
  • blurred vision;
  • headaches;
  • dry nose, mouth, or throat;
  • thick lung secretions;
  • drowsiness;
  • sweating;
  • stomach pain;
  • loss of coordination;
  • constipation.

Rare side effects may include:

  • rapid or irregular heart rate;
  • hyperactivity;
  • low blood pressure;
  • hallucinations;
  • sensitivity to light;
  • difficulty urinating;
  • constipation;
  • erectile dysfunction;
  • blurred or double vision;
  • confusion;
  • seizures;
  • little or no urinating;
  • acute labyrinthitis (inner ear problems);
  • severe allergic reaction;
  • severe drowsiness or dizziness;
  • toxic psychosis;
  • abnormal heart rhythms;
  • low blood cell counts.


Drinking alcoholic beverage while using this medication is not recommended since it increases the risk of side effects.


It is a generic medication that is marketed under numerous brand names, including – Benadryl, Aler-Dryl, 40 Winks, Calm-Aid, Banophen, Diphedryl, Compoz Nighttime Sleep Aid, Diphen, Genahist, Nu-Med, Nytol Caplet, Hydramine, Scot-Tussin Allergy Relief Formula, Quenalin, Sleep, Sleepinal, Twilite, and Sominex.

This medication is an antihistamine that blocks the effects of histamine, a naturally occurring chemical in the human body. It typically starts to work within 60 minutes.

It was first made by George Rieveschlm – an American chemist and professor. In 1946, it became the first US Food and Drug Administration-approved prescription antihistamine and came into commercial use in the same year. It is currently produced by McNeil Healthcare, a division of Johnson & Johnson.


This medication is used in general medicine to treat allergic reactions, allergies, cough, and nausea. Also, it is used to treat motion sickness, certain symptoms of Parkinson’s disease, and to induce sleep.

Moreover, it may help ease joint, bone, or muscle pain from osteoporosis and osteoarthritis, according to a 2013 study issued in the journal Pharmacology. Sometimes, it is prescribed in psychiatric medicine to treat phenothiazine drug-induced abnormal muscle movement.


The usual recommended dose to help with sleep is 25 mg to 50 mg taken by mouth before going to bed. This medication is water-soluble and is absorbed by the human body quickly, reaching the peak level within 60 minutes. Its effects can last for up to 6 hours. It can remain in the body for about 24 hours.

Side Effects and Precautions

Common side effects may include:

  • thickening of bronchial secretions;
  • feeling nervous;
  • blurred vision;
  • mild headaches;
  • constipation;
  • dry nose, mouth, or throat;
  • drowsiness;
  • dizziness.

Rare side effects may include:

  • hypersensitivity;
  • fast or uneven heart rate;
  • severe headaches;
  • rapid pulse;
  • seizure;
  • shortness of breath;
  • chest pain;
  • increased anxiety;
  • severe nervousness;
  • hallucinations;
  • urinating less than usual or not at all;
  • tremor;
  • confusion;
  • blurred vision;
  • unusual weakness;
  • buzzing in the ears;
  • easy bruising or bleeding;
  • dangerously high blood pressure;
  • jaundice (yellowing of the skin or eyes);
  • clay-colored stools;
  • dark urine;
  • loss of appetite;
  • itching;
  • pain in the upper stomach;
  • nausea.

To be sure that this medicine is safe for you to take, tell your healthcare professional if you have other medical conditions, particularly:

  • a thyroid disorder;
  • blockage of the digestive tract (intestines or stomach);
  • if you take potassium (Epiklor, Cytra, Kaon, K-Lyte, K-Phos, Polycitra, Klor-Con, Urocit-K);
  • bladder obstruction or other urination medical problems;
  • glaucoma;
  • an ileostomy or colostomy;
  • low blood pressure;
  • kidney disease;
  • heart disease;
  • liver disease;
  • COPD;
  • chronic bronchitis;
  • emphysema;
  • asthma.


Use alcohol cautiously while taking this medication since it may increase dizziness and drowsiness as well as other side effects.


Because the medication passes into breast milk and may negatively affect the infant, avoid it if you are breastfeeding. According to studies, there is a potential risk to the fetus, therefore, consult your healthcare provider before use especially if you are pregnant or plan to get pregnant.

Drug Interactions

Certain drugs negatively interact with this antihistamine. These include:

  • allergy medications;
  • monoamine oxidase inhibitors used to treat depression;
  • diazepam, a benzodiazepine used to treat seizures, anxiety, and other conditions;
  • prescription pain medications;
  • anxiety medications, like lorazepam (used to treat anxiety disorders and status epilepticus), Welbutrin, alprazolam (Xanax), and temazepam (Restoril);
  • sleeping pills, sedatives, tranquilizers, muscle relaxants, and other medications which are central nervous system depressants.

Doxylamine Succinate vs Diphenhydramine – Which Is Stronger?

Doxylamine Succinate (brand name – Unisom) is an antihistamine medicine that people use to fall asleep and/or stay asleep. This antihistamine can also reduce or prevent allergic reactions by counteracting the effects of a neurotransmitter, called histamine.

Diphenhydramine (brand name – Benadryl) is a first-generation antihistamine that is used to treat a variety of conditions, including allergic symptoms, motion sickness, insomnia (sleep problems), and extrapyramidal symptoms.

According to the data, because it is less likely to breakdown upon ingestion, doxylamine succinate is more powerful than diphenhydramine. However, this also means there is a higher possibility of severe side effects and overdose.

More importantly, due to the lack of efficacy and safety data, the American Academy of Sleep Medicine doesn’t recommend antihistamines for the treatment of chronic insomnia.

Important Note – Don’t Combine These Sedating Antihistamines

Both medications have similar mechanisms of action and produce sedation, therefore, excessive sleepiness can happen if they are taken together.

Image credit – Shutterstock

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