Side Effects of diphenhydramine: A Synthesis of Findings from 29 Studies

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Original Abstract of the Article

Main Research Findings

Diphenhydramine is a commonly used antihistamine medication that is available over-the-counter. However, recent studies have shown that diphenhydramine can have several side effects, including sedation, cardiac toxicity, and the potential for misuse or abuse. 18 , 17 , 11 , 12 , 25 , 5 , 3 , 14 , 2 These studies highlight the need for caution when taking diphenhydramine.

Reasons for Side Effects

Diphenhydramine works by blocking histamine H1 receptors, which are involved in allergic reactions. However, these receptors are also found in the central nervous system, and diphenhydramine's action on these receptors can lead to side effects such as drowsiness and dizziness. 18 , 17 , 11 , 12 , 25 , 5 , 3 , 14 , 2

Common Side Effects

Drowsiness

Diphenhydramine has been reported to cause drowsiness in several studies. 18 , 26 , 4 , 24 , 2 This is likely due to diphenhydramine's effects on the central nervous system, leading to a sedative effect.

Dizziness

Diphenhydramine has been reported to cause dizziness in some studies. 26 , 2 This is likely due to diphenhydramine's effects on the central nervous system, affecting balance and coordination.

Dry Mouth

Diphenhydramine has been shown to cause dry mouth in some studies. 18 This may be caused by diphenhydramine inhibiting saliva production.

Constipation

Diphenhydramine has been reported to cause constipation in some studies. 18 This may be caused by diphenhydramine slowing down bowel movements.

Tachycardia

Diphenhydramine has been associated with an increased heart rate (tachycardia) in some studies. 18 This may be due to diphenhydramine's effects on the heart.

QT Prolongation

Diphenhydramine has been linked to QT prolongation, a potentially serious heart rhythm abnormality. 17 Diphenhydramine may interfere with the electrical activity of the heart, leading to this condition.

Seizures

Diphenhydramine has been reported to cause seizures in some cases. 11 This is thought to be due to diphenhydramine's effects on the central nervous system, increasing excitability.

Other

Diphenhydramine can cause a variety of other side effects including digestive issues, urinary problems, mental and nervous system changes, skin problems, blood abnormalities, and metabolic disorders. 18 , 1 , , 16 , 6 , 9

Side Effects Management

Drowsiness

Avoid driving or operating machinery after taking diphenhydramine. If you experience excessive drowsiness, consult your doctor.

Dizziness

Get up slowly after taking diphenhydramine to prevent dizziness. If you experience severe dizziness, consult your doctor.

Dry Mouth

Stay well-hydrated when taking diphenhydramine.

Constipation

Eat plenty of fiber and drink plenty of fluids when taking diphenhydramine. Consult your doctor if constipation persists.

Tachycardia

Avoid strenuous activity while taking diphenhydramine. If you experience an unusually rapid heartbeat, consult your doctor.

QT Prolongation

If you suspect you may be experiencing QT prolongation, consult your doctor immediately.

Seizures

If you experience a seizure, seek medical attention right away.

Other

If you experience any other side effects, consult your doctor.

Comparison between Studies

Similarities between Studies

Most studies report that diphenhydramine can cause side effects like drowsiness, dizziness, and dry mouth.

Differences between Studies

The specific types and severity of side effects reported in different studies vary. For example, some studies report seizures as a side effect, while others do not. This may be due to differences in study subjects, study methods, or other factors.

Cautions Regarding Real-life Application

Diphenhydramine is an effective medication for treating allergy symptoms, but it can also cause various side effects. Before taking diphenhydramine, discuss the risks and benefits with your doctor. Special caution is needed for pregnant or breastfeeding women, older adults, and people with underlying conditions like heart disease or liver disease.

Limitations of Current Research

While numerous studies have reported diphenhydramine side effects, the mechanisms and preventive measures remain unclear in many cases. Further research is necessary to gain a deeper understanding of diphenhydramine's side effects.

Future Research Directions

As diphenhydramine remains an effective antihistamine with associated side effects, research focusing on mitigating these side effects and improving its safety profile is crucial. This might involve understanding the mechanisms responsible for these side effects and developing alternative medications or strategies to minimize their occurrence.

Conclusion

Diphenhydramine, while effective for allergy relief, carries the potential for side effects like drowsiness, dizziness, and dry mouth. Consult your doctor before taking diphenhydramine to assess the risks and benefits for your specific situation. Future research is necessary to better understand and address the side effects associated with diphenhydramine.

Literature analysis of 29 papers
Positive Content
22
Neutral Content
1
Negative Content
6
Article Type
4
2
2
2
28
1.

Prophylactic Administration of Diphenhydramine to Reduce Neuroleptic Side Effects in the Acute Care Setting: A Systematic Review and Meta-Analysis.

Author: MokhtariAkram, YipOlivia, AlainJudith, BerthelotSimon

Reduced extrapyramidal effects
None reported

Diphenhydramine, when compared to placebo, was associated with a significant reduction in extrapyramidal adverse effects in patients receiving neuroleptic medications. However, the overall quality of evidence is low, and further research is needed.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

4.

Lactobacillus fermentum PS150 promotes non-rapid eye movement sleep in the first night effect of mice.

Author: LinAlexander, ShihChing-Ting, ChuHsu-Feng, ChenChieh-Wen, ChengYu-Ting, WuChien-Chen, YangCheryl C H, TsaiYing-Chieh

Gut microbiota remodeling
Improved sleep

This study investigated the effect of Lactobacillus fermentum PS150 (PS150) on the first night effect (FNE), a sleep disturbance caused by an unfamiliar environment. The findings demonstrate that PS150 effectively ameliorates FNE-induced sleep disturbance in mice, improving sleep duration and reducing sleep latency. The study also suggests that PS150 may modulate gut microbiota composition, contributing to its sleep-enhancing effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Case of acute akathisia from intravenous metoclopramide.

Author: QiuL M, LimB L

Akathisia reversible
Akathisia
Metoclopramide side effect

Acute akathisia, a side effect following IV metoclopramide administration, was successfully managed with IV diphenhydramine and midazolam in a young female patient in the emergency department.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

7.

Diphenhydramine increases the therapeutic window for platinum drugs by simultaneously sensitizing tumor cells and protecting normal cells.

Author: MelnikovaMargarita, WauerUlrike Sophie, MendusDiana, HilgerRalf Axel, OliverTrudy G, MercerKim, GohlkeBjörn Oliver, ErdmannKati, NiederacherDieter, NeubauerHans, BuderathPaul, WimbergerPauline, KuhlmannJan Dominik, ThomaleJürgen

Cisplatin efficacy
Reduced side effects

This study identified diphenhydramine (DIPH) as a pharmacological agent that could enhance cisplatin (CP) efficacy while reducing its side effects. DIPH decreased DNA platination in normal tissues and ameliorated CP-induced toxicity in a mouse model. It also sensitized multiple cancer cell types to CP by increasing intracellular uptake, DNA platination, and/or apoptosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

ABH gel is not absorbed from the skin of normal volunteers.

Author: SmithThomas J, RitterJoseph K, PoklisJustin L, FletcherDevon, CoynePatrick J, DodsonPatricia, ParkerGwendolyn

Nausea treatment
Drug absorption

This study examined whether lorazepam, diphenhydramine, and haloperidol (ABH) topical gel drugs are absorbed.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Prochlorperazine-Induced Hemidystonia Mimicking Acute Stroke.

Author: CoralicZlatan, KimAnthony S, VinsonDavid R

Migraine treatment
Nausea treatment
Hemidystonia
Stroke mimic

This case report describes a pregnant patient taking prochlorperazine for hyperemesis gravidarum who developed hemidystonia, which was initially mistaken for a stroke. This is thought to be the first reported case of prochlorperazine-induced hemidystonia.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

A randomized trial of the effectiveness of topical "ABH Gel" (Ativan(®), Benadryl(®), Haldol(®)) vs. placebo in cancer patients with nausea.

Author: FletcherDevon S, CoynePatrick J, DodsonPatricia W, ParkerGwendolyn G, WanWen, SmithThomas J

Nausea treatment
Limited scientific data

ABH gel, a topical gel containing lorazepam, diphenhydramine, and haloperidol, is often used for nausea but lacks scientific evidence for its effectiveness. Further research is needed to understand why it is perceived to be effective.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Mast cells are critical for protection against peptic ulcers induced by the NSAID piroxicam.

Author: HamptonDaniel D, HaleLaura P

Peptic ulcer prevention
Gastrointestinal toxicity
Peptic ulcers

Mast cell-deficient mice were found to have an extremely high incidence of severe peptic ulceration when exposed to the NSAID piroxicam. This suggests that mast cells and histamine play a critical role in preventing or repairing gastric mucosal injury induced by NSAIDs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

14.

Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications.

Author: HalmoLaurie Seidel, WangGeorge Sam, ReynoldsKate M, Delva-ClarkHeather, Rapp-OlssonMalin, BannerWilliam, BondG Randall, KauffmanRalph E, PalmerRobert B, PaulIan M, GreenJody L, DartRichard C

Fatalities

This study describes fatalities associated with exposures to over-the-counter cough and cold medications in children younger than 12 years old.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Impact of cold and flu medication on obstructive sleep apnoea and its underlying traits: A pilot randomized controlled trial.

Author: Taranto-MontemurroLuigi, SandsScott, AzarbarzinAli, CalianeseNicole, VenaDaniel, HessLauren, KimSang-Wook, WhiteDavid P, WellmanAndrew

OSA treatment
Insomnia

This study aimed to evaluate the effects of a combination of pseudoephedrine, an alpha-1 adrenergic agonist, and diphenhydramine, an antihistaminic-antimuscarinic, on obstructive sleep apnea (OSA). The combination therapy may improve genioglossus muscle activity during sleep and potentially offer a novel treatment option for OSA.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Diphenhydramine and QT prolongation - A rare cardiac side effect of a drug used in common practice.

Author: ShahAditya, YousufTariq, ZiffraJeffrey, ZaidiAli, RaghuvirRashmi

QT prolongation

Diphenhydramine is an antihistamine that can cause QT interval prolongation, a potentially serious heart rhythm problem.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

18.

Diphenhydramine: Time to Move on?

Author: WolfsonAnna R, WongDennis, AbramsElissa M, WasermanSusan, SussmanGordon L

Antihistamine effect
Sedation
Toxicity

This article argues that diphenhydramine, a widely used antihistamine, should be replaced with newer, safer alternatives like second-generation antihistamines, due to its undesirable side effects and availability of more favorable options.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

19.

Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others.

Author: KelleyNancy E, TepperDeborah E

Headache treatment evaluation

This article discusses the effectiveness of various medications for treating headaches in emergency departments, urgent care centers, and headache clinics. The drugs examined include neuroleptics, antihistamines, serotonin antagonists, valproate, octreotide, lidocaine, nitrous oxide, propofol, and bupivacaine.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

20.

Prophylactic Administration of Diphenhydramine to Reduce Neuroleptic Side Effects in the Acute Care Setting: A Systematic Review and Meta-Analysis.

Author: MokhtariAkram, YipOlivia, AlainJudith, BerthelotSimon

Reduced extrapyramidal effects
None reported

Diphenhydramine, when compared to placebo, was associated with a significant reduction in extrapyramidal adverse effects in patients receiving neuroleptic medications. However, the overall quality of evidence is low, and further research is needed.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

21.

Extrapyramidal symptoms following administration of oral perphenazine 4 or 8 mg: an 11-year retrospective analysis.

Author: HenaoJohn P, PeperzakKatherin A, LichvarAlicia B, OrebaughSteven L, SkledarSusan J, PippiMichael A, WilliamsBrian A

PONV prophylaxis
EPS dysfunction

A retrospective analysis of 45,766 patients who received 4 or 8 mg of perphenazine before same-day surgery found four "likely" cases and two "possible" cases of EPS dysfunction. The incidence of EPS dysfunction was 1.3 events per 10,000 patients. All patients who experienced reactions pre-operatively were able to proceed to surgery without complications or delay.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

22.

The Emergency Medicine Pharmacotherapy Literature of 2021.

Author: BrownCaitlin S, SarangarmPreeyaporn, FaineBrett, RechMegan A, FlackTara, GilbertBrian, HowingtonGavin T, LaubJessica, PorterBlake, SlocumGiles W, ZepeskiAnne, ZimmermanDavid E

Agitation management
Appendicitis treatment
Cannabis hyperemsis treatment
Cardiac arrest
Cardiogenic shock
Sepsis management
Stroke treatment

This article highlights the most impactful pharmacotherapy studies published in emergency medicine journals in 2021. It includes summaries of articles on acute agitation, acute appendicitis, sexually transmitted infections, sepsis, stroke, cardiac arrest, and other topics.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

23.

Trends in use of high-risk medications for older veterans: 2004 to 2006.

Author: PughMary Jo V, HanlonJoseph T, WangChen-Pin, SemlaTodd, BurkMuriel, AmuanMegan E, LoweryAshlei, GoodChester B, BerlowitzDan R

High-risk medication use

The study examines the use of high-risk medications for the elderly (HRME) in older outpatient veterans over a three-year period. It aims to assess the changes in HRME use and identify risk factors associated with exposure to these medications.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

24.

An interquartile relationship between polyherbal extract based lozenges linkus a phase IV comparative randomised control trial.

Author: RehmanHina, AliSyed Adnan, NaveedSafila, UsmanghaniKhan

Cough treatment
Side effects

This study compared a herbal cough syrup called Linkus to two pharmaceutical cough syrups containing Acefyllin Piperazine and Aminophylline Diphenhydramine in children. Linkus was found to be significantly more effective at reducing cough frequency and improving sleep in both children and parents. However, the pharmaceutical cough syrups were associated with more side effects.

Clinical Trial, Phase IVPost-marketing surveillance. Monitors long-term safety/efficacy after approval.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

26.

A simulated car-driving study on the effects of acute administration of levocetirizine, fexofenadine, and diphenhydramine in healthy Japanese volunteers.

Author: InamiAkie, MatsudaRin, GroboschThomas, KomamuraHiroshi, TakedaKazuko, YamadaYusuke, MiyakeMasayasu, HiraokaKotaro, MaurerMarcus, YanaiKazuhiko, TashiroManabu

No sedative effects

This study evaluated the sedative effects of levocetirizine, a new-generation antihistamine, in healthy Japanese subjects.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

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