Sage Journals: Discover world-class research

Abstract

Introduction:

This study examined how antihistamine properties of blood-brain barrier penetration, central H₁ receptor binding, and sedative potential—relate to sleep quality, daytime sleepiness, cognitive failures, and functional impairment in adults managed in primary and community health settings, while accounting for sociodemographic, lifestyle, and stress-related factors.

Methods:

A cross-sectional study was conducted in primary care and community health settings using a questionnaire that contained the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Cognitive Failures Questionnaire (CFQ), and Work and Social Adjustment Scale (WSAS). Antihistamine exposure was classified by blood-brain barrier penetration, central H₁ receptor binding, and sedative potential. Multivariable regression analyses were used to identify factors associated with sleep, cognition, and functional outcomes.

Results:

Of the 385 participants, 130 (33.8%) used first-generation antihistamines and 255 (66.2%) used second-generation agents. Of the used antihistamines, 130 (33.8%) were highly sedating, 26 (6.8%) moderately sedating, and 229 (59.5%) nonsedating. Multiple linear regression showed that fixed sleep schedules were associated with less poor sleep (PSQI, B = −0.62, P = .004), while recent stress was associated with worsened sleep quality (B = 0.96, P < .001). Daytime sleepiness (ESS) was significantly associated with higher stress (B = 1.38, P < .001), night-shift work (B = 1.26, P = .003), and sedative properties (B = −1.60, P < .001). Cognitive failures (CFQ) were associated with female sex (B = 4.67, P = .009), higher stress (B = 8.75, P < .001), night-shift work (B = 6.20, P < .001), and sedative properties (B = −5.84, P < .001). Functional impairment (WSAS) was significantly associated with stress (B = 4.43, P < .001), night-shift work (B = 2.62, P = .001), sedative properties (B = −3.21, P < .001), and symptom severity (B = 2.37, P < .001).

Conclusion:

Antihistamine effects on sleep and cognition appear to be shaped by both sedative properties and patient characteristics. These findings suggest that prescribing practices should consider both symptom control and potential impacts on sleep health, cognitive performance, and social functioning, while recognizing that causality cannot be inferred without objective assessments and longitudinal designs.

Keywords

antihistamines sleep quality daytime sleepiness cognitive failures functional impairment stress

Introduction

Antihistamines are widely used to manage different allergic disorders in primary care and community health settings.^1-3 Antihistamines include agents that either penetrate or do not penetrate the blood-brain barrier (BBB); the extent of BBB penetration and central H₁ receptor occupancy determine their sedative potential, which can disrupt nocturnal sleep, heighten daytime sleepiness, and in turn impair cognition and productivity in real-world settings.^4-10 Over the last decade, studies have mapped this terrain with converging evidence across designs. Recent international evidence supports a pragmatic distinction as antihistamines with lower brain penetration tend to better preserve sleep architecture, reduce daytime sleepiness, and mitigate cognitive failures and functional impairment compared to their highly sedating, BBB-penetrating counterparts.^4,5,8-16 Pharmacology and practice updates emphasize minimizing central H₁ receptor engagement to reduce sedation and cognitive slowing, while acknowledging persistent variability across molecules and doses.^4,8-11

In the Palestinian context, antihistamine accessibility is shaped more by availability of generics and formulary decisions than by wide cost differences. First-generation agents such as diphenhydramine and chlorpheniramine remain inexpensive and commonly stocked in community pharmacies, but second-generation agents like loratadine, cetirizine, and fexofenadine are also widely accessible in generic form.^17-19 Local formularies often prioritize supply stability and generic availability, which supports the predominance of nonsedating agents in practice. These contextual factors underscore the importance of balancing clinical efficacy with safety considerations, and they highlight the need for prescribing guidance that accounts for both pharmacological profiles and real-world accessibility in community health systems.

Despite the extensive use of antihistamines and the recognition that patient characteristics can influence sleep and cognitive outcomes, the existing literature has rarely integrated these pharmacological and individual-level determinants into a unified framework. This gap is particularly evident in low- and middle-income regions, where allergic disease burden is high and real-world prescribing patterns often favor second-generation agents without systematic evaluation of their broader impact on daily functioning. This study is guided by a bio-behavioral framework of histaminergic modulation framework that integrates pharmacological properties of antihistamines with individual-level determinants of sleep and cognition. Details of this framework are shown in Supplemental Material and Supplemental Figure S1. The objective of the present study was therefore to investigate the associations between antihistamine use and multidimensional outcomes, sleep quality, daytime sleepiness, cognitive performance, and functional impairment, while simultaneously accounting for patient-level predictors.

Methodology

Study Design and Settings

This study was designed as a cross-sectional, observational investigation conducted in multiple primary care and community health settings in Nablus, Tulkarm, and Jenin regions of the West Bank, Palestine. Data collection took place between September 1st, 2025 and December 20th, 2025. Adherence to the reporting guidelines is shown in Supplemental Table S1.

Participants

Participants were recruited from the participating primary care and community health settings during the study period. Details of the participants, inclusion, exclusion criteria, and sample size calculation are shown in Supplementary materials.

Variables and Data Collection

The study questionnaire was developed directly from the study objectives and informed by a comprehensive review of the literature on antihistamines, sleep quality, daytime sleepiness, cognitive performance, and functional impairment.^2,6,15,20,21 Details of the questionnaire development and validation are shown in Supplemental Material and the final questionnaire is provided as Supplemental Table S2. Patterns of antihistamine use were assessed in terms of type of antihistamine, generation (first vs second), sedative properties, frequency of use, timing of administration, indication, symptom severity, missed dose frequency, and duration of therapy. Antihistamines were classified into first- and second-generation agents. In addition, they were further categorized based on their ability to penetrate the BBB, bind to central H₁ receptors, and induce sedation. Agents known to achieve high BBB penetration and receptor occupancy (>50%), typically associated with marked sedative effects, were classified as highly sedating. Those with intermediate occupancy (about 30%), corresponding to moderate sedative properties, were classified as moderately sedating. By contrast, agents with minimal BBB penetration and low receptor occupancy (< 20%), correlating with negligible sedative effects, were classified as nonsedating. Sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI),²² daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS),²³ cognitive performance using the Cognitive Failures Questionnaire (CFQ),^24,25 and functional impairment was measured using the Work and Social Adjustment Scale (WSAS; Supplemental Table S2). All scales were validated and showed high reliability (Cronbach’s α = .83-.96).

Statistical Analysis

Analyses were performed using IBM SPSS (v21.0). Descriptive statistics summarized participant characteristics. Group differences were tested using t-tests, analysis of variance (ANOVA), and chi-square, with correlations assessed by Pearson’s coefficients (2-tailed P < .05). Because stress, irregular sleep schedules, and pre-sleep electronic device use were highly prevalent in our sample, we first examined their distribution across antihistamine generations in univariate analyses. These variables were then included in multivariable regression models to adjust for their potential confounding effects on sleep, cognition, and functional outcomes. Independently associated factors were identified using multivariable linear regression including antihistamine type, frequency, timing, and confounders. Model diagnostics confirmed robustness (variance inflation factors <2.0, normality, homoscedasticity, and Cook’s distance), and fit was evaluated using F-statistic and adjusted R².

Results

Baseline Characteristics of Participants and Antihistamine Use patterns

Of the 423 individuals invited to participate, 385 completed the study questionnaire and were included in the analysis, yielding a response rate of 91.0% (Supplemental Figure S2). The mean age was 34.0 ± 13.5 years; 59.7% female (Table 1). Most participants were overweight or obese (n = 227, 59.0%), non-smokers (n = 259, 67.3%), and reported daily coffee consumption (n = 173, 44.9%). Pre-sleep electronic exposure (n = 248, 64.4%) and irregular sleep schedules (n = 228, 59.2%) were common, alongside high levels of stress (n = 328, 85.2%) and academic workload (n = 146, 37.9%). Regarding antihistamine use, 130 participants (33.8%) reported first-generation and 255 (66.2%) second-generation agents, primarily for nasal allergy. Nearly half (n = 191, 49.6%) took them at bedtime, with moderate symptom severity (n = 200, 51.9%). Regarding sedative properties, 130 participants (33.8%) used agents with high sedative properties, 26 (6.8%) used agents with moderate sedative properties, and 229 (59.5%) used agents with minimal sedative properties. Details of the antihistamines used by the participants are shown in Supplemental Table S3.

Table 1.

Baseline Characteristics of Participants and Antihistamine Use patterns.

Variable	Subcategory	Mean ± SD or n (%)
Sociodemographic characteristics
Age (years)	Mean ± SD	34.0 ± 13.5
Sex	Male, n (%)	155 (40.3)
Sex	Female, n (%)	230 (59.7)
Employment status	Unemployed, n (%)	234 (60.8)
Employment status	Employed, n (%)	151 (39.2)
Anthropometric characteristics
BMI (kg/m²)	Mean ± SD	26.0 ± 4.3
BMI classification	Normal weight (18.0-24.9 kg/m²), n (%)	158 (41.0)
	Overweight (25.0-29.9 kg/m²), n (%)	165 (42.9)
	Obese (>30 kg/m²), n (%)	62 (16.1)
Lifestyle characteristics
Smoking status	No, n (%)	259 (67.3)
Smoking status	Yes, n (%)	126 (32.7)
Regular exercise	No (<150 min/week), n (%)	251 (65.2)
Regular exercise	Yes (≥150 min/week), n (%)	134 (34.8)
Coffee consumption	Never, n (%)	79 (20.5)
	Sometimes, n (%)	76 (19.7)
	Very often, n (%)	57 (14.8)
	Daily, n (%)	173 (44.9)
Electronics use before sleep	Never, n (%)	21 (5.5)
	Sometimes, n (%)	116 (30.1)
	Always, n (%)	248 (64.4)
Fixed sleep schedule	Never, n (%)	45 (11.7)
	Sometimes, n (%)	183 (47.5)
	Always, n (%)	157 (40.8)
Stress, workload, and circadian strain
Stress in the last month	Never, n (%)	57 (14.8)
	Sometimes, n (%)	247 (64.2)
	Always, n (%)	81 (21.0)
Night shift work	Never, n (%)	303 (78.7)
	Sometimes, n (%)	63 (16.4)
	Always, n (%)	19 (4.9)
Student with exam burden	Never, n (%)	239 (62.1)
	Sometimes, n (%)	55 (14.3)
	Always, n (%)	91 (23.6)
Patterns of antihistamine use
Antihistamine generation	First generation, n (%)	130 (33.8)
Antihistamine generation	Second generation, n (%)	255 (66.2)
Sedative properties	High BBB penetration and H₁ receptor occupancy (>50%), correlating with marked sedative properties, n (%)	130 (33.8)
	Moderate BBB penetration and H₁ receptor occupancy (~30%), correlating with moderate sedative properties, n (%)	26 (6.8)
	Minimal BBB penetration and H₁ receptor occupancy (< 20%), correlating with minimal sedative properties, n (%)	229 (59.5)
Frequency of use	Daily, n (%)	96 (24.9)
	Three to five times/week, n (%)	55 (14.3)
	Once or twice/week, n (%)	40 (10.4)
	Only when needed, n (%)	194 (50.4)
Time of administration	Morning, n (%)	38 (9.9)
	Afternoon, n (%)	19 (4.9)
	Evening, n (%)	137 (35.6)
	Before sleep, n (%)	191 (49.6)
Indication for use	Nasal allergy, n (%)	251 (65.2)
	Chest allergy, n (%)	38 (9.9)
	Skin allergy, n (%)	56 (14.5)
	Urticaria, n (%)	36 (9.4)
	To help with sleep, n (%)	4 (1.0)
Symptom severity	Mild, n (%)	135 (35.1)
	Moderate, n (%)	200 (51.9)
	Severe, n (%)	50 (12.9)
Missed dose frequency	Never, n (%)	94 (24.4)
	Sometimes, n (%)	275 (71.4)
	Often, n (%)	16 (4.2)
Duration of antihistamine use (years)	Mean ± SD	1.5 ± 2.7

Abbreviations: BBB, blood-brain barrier; BMI, body mass index; SD, standard deviation.

Sleep Quality, Daytime Sleepiness, Cognitive Failure, and Functional Impairment

Supplemental Tables S4 to S7 present PSQI responses, showing distributions for sleep latency, duration, efficiency, disturbances, and use of sleep medication. Despite average sleep durations approaching 7 h, many participants reported difficulty initiating sleep, frequent nocturnal awakenings, and environmental or physiological disruptions such as snoring, breathing problems, or pain. Supplemental Tables S8 and S9 present ESS responses, documenting the likelihood of dozing across everyday situations. They reveal that daytime somnolence was common, particularly during passive activities such as reading or watching television, underscoring the functional consequences of sedating antihistamines. CFQ items captured lapses in memory, attention, and perception (Supplemental Tables S10-S13). Participants reported forgetting appointments, misplacing objects, and losing concentration were frequent, with higher scores clustering among users of sedating antihistamines and those reporting stress or night-shift work. WSAS domains showed impairment in occupational tasks, social activities, and family responsibilities (Supplemental Tables S14-S16). WSAS scores demonstrated that functional disruption was not only statistically significant but clinically meaningful, with many participants reporting moderate to severe interference in daily life.

Factors Associated with Deteriorated Sleep Quality, Daytime Sleepiness, Cognitive Failure, and Functional Impairment

Table 2 summarizes the multiple linear regression analyses examining factors associated with deteriorated sleep quality (PSQI), daytime sleepiness (ESS), cognitive failures (CFQ), and functional impairment (WSAS). Model diagnostics are shown in Supplementary materials. Across all models, psychosocial stress consistently emerged as the strongest factors, significantly associated with worsening sleep quality (B = 0.96, P < .001), increasing daytime sleepiness (B = 1.38, P < .001), elevating cognitive failures (B = 8.75, P < .001), and amplifying functional impairment (B = 4.43, P < .001). Irregular sleep schedules were associated with poorer sleep quality (B = −0.62, P = .004). Night-shift work was associated with higher ESS scores (B = 1.26, P = .003), greater CFQ scores (B = 6.20, P < .001), and more severe functional impairment (B = 2.62, P = .001).

Table 2.

Factors Predicting Sleep Quality, Daytime Sleepiness, Cognitive Failure, and Functional Impairment.

Variable	Unstandardized coefficients		Standardized coefficients	t	P-value	95% confidence interval for B		Collinearity statistics
Variable	B	SE	Beta	t	P-value	Lower bound	Upper bound	Tolerance	VIF
Factors associated with PSQI scores
Age	0.00	0.01	.01	0.16	.871	−0.02	0.03	0.60	1.68
Electronics use before sleep	0.30	0.25	.06	1.17	.243	−0.20	0.79	0.88	1.14
Fixed sleep schedule	−0.62	0.22	−.14	−2.89	.004	−1.05	−0.20	0.96	1.04
Stress in the last month	0.96	0.25	.20	3.89	<.001	0.47	1.44	0.91	1.09
Student with exam burden	0.24	0.21	.07	1.16	.245	−0.17	0.66	0.63	1.58
Antihistamine frequency of use/week	0.15	0.11	.07	1.34	.182	−0.07	0.37	0.98	1.02
Factors associated with ESS scores
Stress in the last month	1.38	0.37	.17	3.69	<.001	0.64	2.11	0.99	1.01
Night-shift work	1.26	0.42	.14	3.01	.003	0.44	2.08	0.95	1.05
Sedative properties (high vs moderate vs nonsedating)	−1.60	0.24	−.31	−6.56	<.001	−2.08	−1.12	0.95	1.06
Time of administration (day vs night)	−0.06	0.24	−.01	−0.24	.808	−0.52	0.41	0.99	1.01
Factors associated with CFQ scores
Sex (female vs male)	4.67	1.78	.12	2.62	.009	1.17	8.17	0.86	1.16
Age (years)	−0.03	0.08	−.03	−0.45	.654	−0.18	0.11	0.62	1.60
Stress in the last month	8.75	1.42	.28	6.15	<.001	5.95	11.55	0.92	1.09
Night-shift work	6.20	1.58	.18	3.91	<.001	3.09	9.32	0.90	1.12
Student with exam burden	0.28	1.24	.01	0.22	.822	−2.15	2.71	0.61	1.65
Sedative properties (high vs moderate vs nonsedating)	−5.84	0.90	−.30	−6.51	<.001	−7.61	−4.08	0.94	1.06
Time of administration (day vs night)	0.53	0.89	.03	0.59	.554	−1.22	2.28	0.94	1.06
Factors associated with WSAS scores
Stress in the last month	4.43	0.67	.29	6.59	<.001	3.11	5.76	0.98	1.02
Night-shift work	2.62	0.75	.16	3.48	.001	1.14	4.10	0.95	1.05
Sedative properties (high vs moderate vs nonsedating)	−3.21	0.44	−.33	−7.29	<.001	−4.07	−2.34	0.94	1.07
Antihistamine use during the day	−0.18	0.43	−.02	−0.42	.678	−1.02	0.66	0.98	1.02
Symptom severity	2.37	0.62	.17	3.85	<.001	1.16	3.58	0.96	1.04
Missed dose frequency	−0.04	0.81	.00	−0.05	.964	−1.63	1.55	0.98	1.02

Abbreviations: B, unstandardized coefficient; Beta, standardized coefficient; CFQ, cognitive failures questionnaire; CI, confidence interval; ESS, Epworth sleepiness scale; PSQI, Pittsburgh sleep quality index; SE, standard error; VIF, variance inflation factor; WSAS, work, and social adjustment scale.

Statistically significant P-values are in boldface.

Antihistamine with high BBB penetration and central H₁ receptor occupancy were significantly associated with greater daytime sleepiness (B = −1.60, P < .001), more cognitive failures (B = −5.84, P < .001), and higher functional impairment (B = −3.21, P < .001). Symptom severity was associated with functional impairment (B = 2.37, P < .001). Sex differences were evident, with females reporting higher CFQ scores (B = 4.67, P = .009). Other variables, including age and caffeine consumption, were not significantly associated in the adjusted models.

Correlation Between Sleep Quality, Daytime Sleepiness, Cognitive Failures, and Functional Impairment

The correlation analysis revealed significant associations among the different scales. Poor sleep quality, as measured by the PSQI, was modestly but significantly correlated with greater daytime sleepiness (ESS, Pearson’s r = .141, P = .006), more frequent cognitive failures (CFQ, Pearson’s r = .146, P = .004), and higher levels of functional impairment (WSAS, Pearson’s r = .305, P < .001). Daytime sleepiness showed a positive correlation with cognitive failures (Pearson’s r = .601, P < .001) and functional impairment (Pearson’s r = .559, P < .001), suggesting that excessive sleepiness is associated with both cognitive lapses and difficulties in daily functioning. Likewise, cognitive failures were correlated with functional impairment (Pearson’s r = .649, P < .001), suggesting that individuals reporting more frequent cognitive lapses also experienced greater disruption in work and social adjustment. Overall, these findings highlight a network of associations in which poor sleep quality, excessive sleepiness, and cognitive difficulties converge to exacerbate functional impairment.

Discussion

This study provides the first evidence from Palestinian practice on how antihistamine properties and patient-level factors jointly shape sleep, cognition, and daily functioning. Agents with high central H₁ receptor occupancy and sedative effects were consistently associated with greater daytime sleepiness, cognitive failures, and functional impairment. Psychosocial stress emerged as a strong factor across all outcomes, worsening nocturnal sleep quality, alertness, cognition, and functional adjustment, whereas maintaining fixed sleep schedules was protective. These findings underscore the cumulative burden of pharmacological sedation and lifestyle stressors. Consistent with prior evidence, BBB penetration and H₁ receptor blockade were linked to disrupted sleep architecture, including prolonged latency and reduced slow-wave sleep, while stress-induced hyperarousal further fragmented sleep.^{2,4,6,10,11,15} These effects were compounded by irregular sleep schedules, night-shift work, and pre-sleep electronic device use. Prior studies confirm similar patterns, with sedating antihistamines worsening subjective sleep despite symptom relief and stress-induced hyperarousal fragmenting sleep.^2,26 Together, the evidence highlights the need for healthcare providers, pharmacists, and policymakers to balance allergy symptom control with the preservation of sleep health, cognition, and daily functioning.

Daytime sleepiness was greater among users of sedating antihistamines, consistent with their pharmacodynamic profile of reduced cortical arousal.^{7,8,10,11,16,21} Stress and night-shift work likely magnified this effect, and prior ESS-based studies report comparable findings, including residual next-day sedation.^9-11 Clinically, this underscores the importance of tailoring prescriptions to occupational and lifestyle demands, particularly in safety-critical roles.^4,7,12,21,27 Cognitive failures were likewise higher among users of sedating agents, reflecting sustained disruptions in attention and executive function. Stress and night-shift exposure were key associated factors, echoing prior CFQ-based studies linking first-generation agents to impaired vigilance and workplace errors.^4,11,28,29 Functional impairment extended these effects into daily life, with sedating antihistamines consistently associated with reduced occupational performance, social participation, and family responsibilities.^{4,11,25,28,29} Stress compounded these disruptions, underscoring the cumulative toll of pharmacological sedation and psychosocial strain. Taken together, BBB-penetrating antihistamines with strong central H1 binding disrupted sleep, increased daytime sleepiness, and amplified cognitive failures, translating into measurable functional impairment. However, some studies report minimal next-day sedation with certain first-generation agents, suggesting inter-drug variability may attenuate cognitive and functional impairment.^11,14

In resource-limited or high-volume primary care settings, integrating these findings into routine workflows can enhance both efficiency and patient safety. Brief screening questions on sleep quality, daytime alertness, and cognitive lapses can be incorporated into intake forms or nurse-led triage with minimal added burden. Decision-support prompts within prescribing workflows may help clinicians identify patients at risk of sedation-related impairment and consider nonsedating alternatives when appropriate. Embedding lifestyle counseling—such as stress management, regular sleep schedules, and reduced pre-sleep device use—into routine patient education can further mitigate risks. Aligning these practices with existing community health workflows enables providers to balance allergy symptom control with the preservation of sleep health, cognitive performance, and daily functioning, even in settings constrained by limited resources and high patient volumes.

Limitations of the Study

This study has several limitations. First, its cross-sectional design precludes causal inference, and reliance on self-reported measures introduces potential recall bias. Second, objective sleep assessments (eg, polysomnography) were not included, limiting external validity. Third, although strict inclusion and exclusion criteria were applied—excluding patients with major neurological or psychiatric conditions, diagnosed sleep disorders, or concurrent use of sedative/hypnotic medications—residual confounding from unmeasured factors such as comorbidities, medication use beyond antihistamines, disease severity, or socioeconomic stressors cannot be fully excluded. While symptom severity items were incorporated to partially adjust for indication, residual confounding remains possible. Fourth, psychosocial and lifestyle factors such as stress, irregular sleep schedules, and electronic device use may also confound associations. However, their prevalence was similar across antihistamine groups, and regression models adjusted for these factors, reducing the likelihood that uneven distribution explains the observed differences. Fifth, BMI and smoking status were analyzed but did not show associations with sleep or cognitive outcomes, suggesting that psychosocial stressors and type of antihistamine exerted stronger effects in this sample. Future studies with larger cohorts and objective measures may clarify the role of these factors. Sixth, baseline imbalance between users of first- and second-generation antihistamines cannot be fully excluded. Although cluster sampling and multivariable adjustment were employed, residual differences in baseline characteristics may have influenced associations. Sensitivity analyses for borderline or self-reported comorbidities were not conducted, which may also have affected outcomes. In addition, although cluster sampling was used across multiple primary care and community health settings, design-based analytic techniques (eg, weighting or stratification) were not applied. As a result, extrapolation to broader populations should be made cautiously. Future research should employ longitudinal designs, objective sleep monitoring, stratified sampling, and analytic methods that incorporate sampling weights to strengthen causal inference, external validity, and generalizability.

Conclusion

This study shows that antihistamine effects on sleep, cognition, and daily functioning depend on BBB penetration, central H₁ receptor binding, patient-level factors such as stress and circadian irregularity. In Palestinian primary care, sedating agents were linked to poorer sleep, greater daytime sleepiness, more cognitive failures, and higher functional impairment, while nonsedating agents—widely available through generics and formulary prioritization—were comparatively safer. The predominance of second-generation use in practice aligns with international evidence and underscores the importance of continuing this prescribing pattern. These findings suggest that allergy management should balance symptom relief with protection of sleep health, cognitive performance, and daily functioning, guiding clinicians and policymakers toward safer, evidence-based choices.

Supplemental Material

sj-docx-1-jpc-10.1177_21501319261442260 – Supplemental material for Impact of Antihistamines on Sleep, Cognition, and Daily Functioning: Evidence From Primary and Community Care

Supplemental material, sj-docx-1-jpc-10.1177_21501319261442260 for Impact of Antihistamines on Sleep, Cognition, and Daily Functioning: Evidence From Primary and Community Care by Othman Jaradat, Adan Awad, Hadeel Abu Samaan, Sara Al-Toom, Taysir Alsadder, Mohammad Jaber and Ramzi Shawahna in Journal of Primary Care & Community Health

Footnotes

Acknowledgements

An-Najah National University (www.najah.edu) and An-Najah National University Hospital () are acknowledged for making this study possible. The authors would like to thank the study participants and the participating primary and community healthcare centers.

ORCID iDs

Othman Jaradat

Ramzi Shawahna

Ethical Considerations

This study was conducted in strict adherence to both international and local ethical principles, including the guidelines set forth in the Declaration of Helsinki and its subsequent amendments. Ethical approval was obtained from the Institutional Review Board (IRB) of An-Najah National University under approval number Med. Jan. 2025/36 prior to the initiation of data collection. All participants were fully informed about the purpose, procedures, potential risks, and benefits of the study. They were assured that participation was entirely voluntary and that they retained the right to withdraw at any time without consequence. Confidentiality of personal information was guaranteed, with data stored securely and accessible only to the research team.

Consent to Participate

Written informed consent was obtained from each participant before enrollment. The consent process emphasized transparency, ensuring that participants understood the scope of the study and the intended use of their data for academic and scientific purposes.

Author Contributions

Study concept and design: Ramzi Shawahna, Mohammad Jaber, and Taysir Alsadder. Acquisition of data: Othman Jaradat, Adan Awad, and Shadi Nassar. Analysis and interpretation of data: Ramzi Shawahna, Mohammad Jaber, Taysir Alsadder, Othman Jaradat, Adan Awad, and Shadi Nassar. Drafting of the manuscript: Ramzi Shawahna, Mohammad Jaber, Taysir Alsadder, Othman Jaradat, Adan Awad, and Shadi Nassar. Critical revision of the manuscript for important intellectual content: Ramzi Shawahna, Mohammad Jaber, Taysir Alsadder, Othman Jaradat, Adan Awad, and Shadi Nassar. Statistical analysis: Ramzi Shawahna, Othman Jaradat. Supervision: Ramzi Shawahna, Mohammad Jaber, and Taysir Alsadder.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

Data is available upon request from the corresponding author*.

Supplemental Material

Supplemental material for this article is available online.

Generative AI Disclosure

In line with the journal’s policy on transparency, the authors wish to declare that during the preparation of the manuscript, the authors used Grammarly (Superhuman Platform Inc., San Francisco, California), Copilot (Microsoft Inc., Redmond, Washington), and ChatGPT (OpenAI, San Francisco, California) solely to edit the language and improve grammar, spelling, punctuation, readability, and style of the manuscript. After using these tools/services, the authors reviewed and edited the content as needed and take full responsibility for the scientific content, accuracy, and integrity of the manuscript. Artificial intelligence tools/services were not used for generative editorial work, autonomous content creation, data analysis, statistical interpretation, or the generation of scientific content.

References

Shamil

Prakruti

Anuradha

Bela

Chetna

KD.

Old versus new antihistamines: effects on cognition and psychomotor functions. J Fam Med Primary Care. 2022;11(10): 5909-5917. doi:10.4103/jfmpc.jfmpc_77_22

Sato

Tareishi

Suzuki

Ansai

Asaka

Ohta

Effect of second-generation antihistamines on nighttime sleep and daytime sleepiness in patients with allergic rhinitis. Sleep Breath. 2023;27(6):2389-2395. doi:10.1007/s11325-023-02857-6

Linton

Hossenbaccus

Ellis

AK.

Evidence-based use of antihistamines for treatment of allergic conditions. Ann Allergy Asthma Immunol. 2023;131(4):412-420. doi:10.1016/j.anai.2023.07.019

Ansotegui

Bousquet

Canonica

, et al. Why fexofenadine is considered as a truly non-sedating antihistamine with no brain penetration: a systematic review. Curr Med Res Opin. 2024;40(8):1297-1309. doi:10.1080/03007995.2024.2378172

Chu

Zhao

Rayner

, et al. First-generation vs second-generation H1 antihistamines for chronic urticaria: systematic review and network meta-analysis. J Allergy Clin Immunol. 2026;157(2):AB31. doi:10.1016/j.jaci.2025.12.096

Kawauchi

Yanai

Wang

Itahashi

Okubo

Antihistamines for allergic rhinitis treatment from the viewpoint of nonsedative properties. Int J Mol Sci. 2019;20(1):213. doi:10.3390/ijms20010213

Wasim

Miriyala

Haward

, et al. Sleep disturbance and chronic urticaria: a narrative review of its relationship, treatment and evolving literature. Health Sci Rep. 2025;8(5): e70777. doi:10.1002/hsr2.70777

Wolfson

Wong

Abrams

Waserman

Sussman

GL.

Diphenhydramine: time to move on?

J Allergy Clin Immunol Pract. 2022;10(12):3124-3130. doi:10.1016/j.jaip.2022.07.018

Chaudhari

Gosavi

Bornare

Sonawane

Ahire

An overview of antihistamines and their properties used for treatment of different diseases. Antiinflamm Antiallergy Agents Med Chem. 2023;22(4):220-229. doi:10.2174/0118715230259623231111165759

10.

Tay

Zhao

Allen

Yew

Tey

HL.

Effectiveness of antihistamines for itch and sleep disturbance in atopic dermatitis: a retrospective cohort study. Itch. 2021;6(2):e47. doi:10.1097/itx.0000000000000047

11.

Zhang

Tashiro

Shibuya

, et al. Next-day residual sedative effect after nighttime administration of an over-the-counter antihistamine sleep aid, diphenhydramine, measured by positron emission tomography. J Clin Psychopharmacol. 2010;30(6):694-701. doi:10.1097/jcp.0b013e3181fa8526

12.

Bonnesen

Romer

Graff Jensen

, et al. Sedating antihistamine treatment with promethazine in patients with severe COPD with and without asthma: death and severe exacerbations in a nationwide register study. Eur Clin Respir J. 2023; 10(1):2250604. doi:10.1080/20018525.2023.2250604

13.

Hindmarch

Shamsi

Antihistamines: models to assess sedative properties, assessment of sedation, safety and other side-effects. Clin Exp Allergy. 1999;29 Suppl 3:133-142. doi:10.1046/j.1365-2222.1999.0290s3133.x

14.

Isomura

Kono

Hindmarch

, et al. Central nervous system effects of the second-generation antihistamines marketed in Japan–review of inter-drug differences using the proportional impairment ratio (PIR). PLoS ONE. 2014;9(12):e114336. doi:10.1371/journal.pone.0114336

15.

Ozdemir

Karadag

Selvi

, et al. Assessment of the effects of antihistamine drugs on mood, sleep quality, sleepiness, and dream anxiety. Int J Psychiatry Clin Pract. 2014; 18(3):161-168. doi:10.3109/13651501.2014.907919

16.

Xiang

Fok

Podder

, et al. An update on the use of antihistamines in managing chronic urticaria. Exp Opin Pharmacother. 2024;25(5):551-569. doi:10.1080/14656566.2024.2345731

17.

Nair

KV.

Prescription to over-the-counter switch of second-generation antihistamines (loratadine). Dis Manag Health Outcomes. 2006;14(2):69-74. doi:10.2165/00115677-200614020-00001

18.

Liao

Leahy

Cummins

The costs of nonsedating antihistamine therapy for allergic rhinitis in managed care: an updated analysis. Am J Manag Care. 2001;7(15 Suppl): S459-S468.

19.

Sun

Jing

Lee

McMurray

Young

Impact of formulary management and step therapy for non-sedating antihistamines on prescription drug utilisation and costs. J Med Econ. 2007;10(4):367-378. doi:10.3111/13696990701640653

20.

Acar

Cingi

Sakallioglu

San

Fatih Yimenicioglu

Bal

The effects of mometasone furoate and desloratadine in obstructive sleep apnea syndrome patients with allergic rhinitis. Am J Rhinol Allergy. 2013;27(4):e113-e116. doi:10.2500/ajra.2013.27.3921

21.

Woods

Craig

TJ.

The importance of rhinitis on sleep, daytime somnolence, productivity and fatigue. Curr Opin Pulm Med. 2006;12(6):390-396. doi:10.1097/01.mcp.0000245710.43891.5f

22.

Buysse

Reynolds

3rd Monk

Berman

Kupfer

DJ.

The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2): 193-213. doi:10.1016/0165-1781(89)90047-4

23.

Johns

MW.

A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-545. doi:10.1093/sleep/14.6.540

24.

Broadbent

Cooper

FitzGerald

Parkes

KR.

The Cognitive Failures Questionnaire (CFQ) and its correlates. Br J Clin Psychol. 1982;21(1):1-16. doi:10.1111/j.2044-8260.1982.tb01421.x

25.

Mundt

Marks

Shear

Greist

JH.

The Work and Social Adjustment Scale: a simple measure of impairment in functioning. Br J Psychiatry. 2002;180:461-464. doi:10.1192/bjp.180.5.461

26.

Clark

Landolt

HP.

Coffee, caffeine, and sleep: a systematic review of epidemiological studies and randomized controlled trials. Sleep Med Rev. 2017;31:70-78. doi:10.1016/j.smrv.2016.01.006

27.

Blaiss

Bernstein

Kessler

, et al. The role of cetirizine in the changing landscape of IV antihistamines: a narrative review. Adv Ther. 2022;39(1):178-192. doi:10.1007/s12325-021-01999-x

28.

Sagara

Nagahama

Aki

, et al. Potential risk of driving performance under combined conditions of taking second-generation antihistamines and attending calls using a hands-free function. Traffic Inj Prev. 2024;25(1):36-40. doi:10.1080/15389588.2023.2265002

29.

Vieira

Pham-Thi

Anto

, et al. Academic productivity of young people with allergic rhinitis: a MASK-air study. J Allergy Clin Immunol Pract. 2022;10(11):3008-3017.e4. doi:10.1016/j.jaip.2022.08.015

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.25 MB

0.00 MB

Impact of Antihistamines on Sleep,Cognition,and Daily Functioning: Evidence From Primary and Community Care

Abstract

Introduction:

Methods:

Results:

Conclusion:

Keywords

Introduction

Methodology

Study Design and Settings

Participants

Variables and Data Collection

Statistical Analysis

Results

Baseline Characteristics of Participants and Antihistamine Use patterns

Sleep Quality, Daytime Sleepiness, Cognitive Failure, and Functional Impairment

Factors Associated with Deteriorated Sleep Quality, Daytime Sleepiness, Cognitive Failure, and Functional Impairment

Correlation Between Sleep Quality, Daytime Sleepiness, Cognitive Failures, and Functional Impairment

Discussion

Limitations of the Study

Conclusion

Supplemental Material

sj-docx-1-jpc-10.1177_21501319261442260 – Supplemental material for Impact of Antihistamines on Sleep, Cognition, and Daily Functioning: Evidence From Primary and Community Care

Footnotes

Acknowledgements

ORCID iDs

Ethical Considerations

Consent to Participate

Author Contributions

Funding

Declaration of Conflicting Interests

Data Availability Statement

Supplemental Material

Generative AI Disclosure

References

Supplementary Material