Polypharmacy-Related Psychological Distress Scale

Abstract

The management of multiple concurrent medications, clinically operationalized as polypharmacy, represents an escalating public health phenomenon driven by population aging and the compounding prevalence of chronic multimorbidity. Although the biomedical and physiological hazards of polypharmacy—such as severe adverse drug reactions, cumulative drug interactions, cognitive impairment, and physical falls—are well documented in the pharmacotherapeutic literature, the subjective affective and cognitive toll experienced by patients has historically remained neglected. The Polypharmacy-Related Psychological Distress Scale (PPDS) was specifically engineered by Cheng Cheng, Xiao Chen, Junqiao Wang, and Martin Christensen to address this empirical and clinical void. Designed as an ultra-brief, four-item patient-reported outcome measure (PROM), the PPDS captures the idiosyncratic emotional strain, logistical overwhelm, and anticipatory anxiety directly engendered by managing complex medication regimens.

Grounded in the biopsychosocial model, the Burden of Treatment Theory, and Leventhal’s Common-Sense Model of Self-Regulation, the PPDS operationalizes polypharmacy-induced distress as a unidimensional latent construct. Psychometric evaluation in a clinical cohort of multimorbid adults and older adults ($N = 97$, with 91 complete responses) demonstrated robust internal consistency, yielding a Cronbach’s alpha of 0.790 and a McDonald’s omega ($\omega$) of 0.937. Confirmatory factor analysis verified a parsimonious single-factor structure with exceptional goodness-of-fit indices: Comparative Fit Index (CFI) = 0.986, Tucker-Lewis Index (TLI) = 0.987, Standardized Root Mean Square Residual (SRMR) = 0.040, and Root Mean Square Error of Approximation (RMSEA) = 0.060. Concurrent validity was established via a moderate, statistically significant positive correlation with the Patient Health Questionnaire-4 ($r = 0.444$), confirming that the PPDS measures a distinct, domain-specific affective state rather than general negative affectivity. This scale provides clinicians and clinical researchers with an efficient, sensitive diagnostic tool for routine clinical workflows, medication reconciliation, and deprescribing clinical trials.

Keywords

Polypharmacy, Psychological Distress, Medication Burden, Biopsychosocial Model, Burden of Treatment Theory, Health Psychology, Psychometrics, Geriatrics, Deprescribing, Patient-Reported Outcome Measures, Multimorbidity, Confirmatory Factor Analysis

Authors

The Polypharmacy-Related Psychological Distress Scale (PPDS) was conceptualized, developed, and psychometrically validated by an interdisciplinary team of clinical researchers specializing in geriatric nursing, health psychology, and internal medicine:

• Cheng Cheng, PhD, RN (Corresponding Author): School of Nursing, Fudan University, Shanghai, China. Primary clinical research focuses on geriatric health, chronic disease self-management, medication-related burden, and psychometric development in aging populations. Contact Email: [email protected].
• Xiao Chen: School of Nursing, Fudan University, Shanghai, China. Specialized in clinical nursing interventions, multimorbidity management, and quantitative health psychology methodologies.
• Junqiao Wang, PhD, RN: School of Nursing, Fudan University, Shanghai, China. Expert in oncological and chronic care nursing, patient-reported outcome measures, and mixed-methods health services research.
• Martin Christensen, PhD, RN: International collaborator and academic scholar contributing theoretical and methodological expertise in critical care, gerontological patient outcomes, and international clinical assessment practices.

Purpose

For several decades, pharmacotherapeutic assessments in chronic disease management have been predominantly biomedical, functional, and behavioral. Standard tools routinely deployed in clinical practice focus almost exclusively on objective metrics, such as counting daily pill quantities, utilizing the Medication Regimen Complexity Index (MRCI) to score logistical difficulty, or assessing behavioral adherence using compliance scales like the Morisky Medication Adherence Scale (MMAS-8) or the Medication Adherence Report Scale (MARS). While these indices provide indispensable information regarding pharmacodynamics and patient compliance, they systematically overlook the subjective internal experience of the patient. The primary purpose of the Polypharmacy-Related Psychological Distress Scale (PPDS) is to directly assess, quantify, and track the psychological and emotional sequelae imposed by polypharmacy regimens.

As global healthcare systems contend with unprecedented rates of multimorbidity—where individuals simultaneously manage hypertension, type 2 diabetes, ischemic heart disease, osteoarthritis, and chronic respiratory disorders—clinical guidelines frequently advocate for disease-specific multi-drug therapy. Consequently, older adults are routinely prescribed 5, 10, or even 15 concurrent daily medications. This pharmacological proliferation induces a distinct cluster of psychological stressors: constant fear of adverse drug reactions, anticipatory anxiety concerning strict precautions (e.g., meal timings, hydration requirements, contraindications), logistical exhaustion, and an acute perceived loss of autonomy. When healthcare professionals fail to recognize this burden, patients may experience profound “treatment fatigue,” precipitating unguided self-discontinuation of life-sustaining drugs, accidental overdoses, exacerbation of depressive symptoms, or systemic alienation from the healthcare system.

The PPDS was specifically engineered to address these challenges in both clinical practice and interventional research. In clinical workflows, its ultra-brief 4-item format enables seamless integration into routine primary care consultations, geriatric outpatient assessments, and clinical pharmacy reviews without imposing cognitive exhaustion upon vulnerable patients. Identification of high polypharmacy-related distress empowers physicians and pharmacists to initiate timely deprescribing protocols, simplify complicated dosing schedules, synchronize prescription refill timelines, and refer individuals to targeted psychogeriatric support. In academic research, the PPDS serves as a standardized, responsive outcome measure for evaluating the efficacy of patient-centered medication therapy management (MTM) interventions, deprescribing trials, and integrated chronic care delivery models.

Psychological Construct

The psychological construct measured by the PPDS is defined as polypharmacy-related psychological distress: an acute or persistent negative affective and cognitive state directly provoked by the ongoing demands, complexities, uncertainties, and identity disruptions associated with taking multiple concurrent prescription medications. Rather than conceptualizing medication burden as merely an external administrative chore, the construct focuses on how these external tasks penetrate the patient’s psychological ecosystem, generating chronic distress.

Although the PPDS operationalizes this distress as an overarching unidimensional latent trait, the construct encompasses several interconnected cognitive and emotional facets that coalesce within the patient’s lived experience:

• Cognitive and Logistical Overwhelm: The subjective cognitive load required to organize, track, remember, and physically ingest complex combinations of pills, capsules, inhalers, and injections throughout the day. Patients report feeling mentally drained by continuous self-monitoring, managing differing storage requirements, and parsing dense warning labels.
• Anticipatory Anxiety and Somatic Hypervigilance: A pervasive, ongoing fear regarding potential adverse drug reactions, toxic drug-drug interactions, and organ damage (particularly hepatic and renal toxicity). This facet manifests as heightened somatic vigilance, wherein benign bodily sensations are interpreted catastrophically as side effects of their medication regimen.
• Precautionary Stress: The emotional strain of adhering to rigid conditional instructions, such as taking specific tablets on an empty stomach, waiting designated intervals before ingesting food, avoiding certain dietary ingredients, or monitoring blood pressure and glucose before administration. The fear of making an error creates persistent, anticipatory performance anxiety.
• Erosion of Autonomy and Medicalization of Self: The internal feeling that one’s daily rhythm, identity, and personal agency are dictated entirely by pharmaceutical schedules. Patients often perceive their bodies as failing machines dependent upon chemical sustenance, triggering feelings of vulnerability, demoralization, and perceived frailty.

The PPDS captures this multifaceted experiential domain through a parsimonious four-item structure. Crucially, the construct does not represent generalized clinical depression or generalized anxiety disorder; rather, it reflects a specific, context-bound psychological response directly attributable to medical therapy. By retaining items that gauge anticipatory worry regarding precautions and adverse consequences alongside daily logistical strain, the latent construct encapsulates both the immediate behavioral stress and the existential health-related anxieties intrinsic to polypharmacy.

Theoretical Framework

The conceptual architecture of the Polypharmacy-Related Psychological Distress Scale is firmly anchored in three complementary theoretical frameworks within behavioral medicine and health psychology: the Biopsychosocial Model, the Burden of Treatment Theory, and Leventhal’s Common-Sense Model of Self-Regulation.

The Biopsychosocial Model

Pioneered by George L. Engel in the late 1970s and early 1980s, the biopsychosocial model posits that biological phenomena cannot be examined in isolation from psychological processes and sociocultural environments. In pharmacotherapy, conventional medicine has operated under a strict biomedical paradigm: a disease pathology arises, and pharmacological agents are introduced to correct the biological dysfunction. However, the biopsychosocial model illuminates the psychological reality that pharmaceutical agents themselves function as psychological stimuli. Every additional prescription alters the patient’s psychological perception of their health status, alters social interactions (e.g., avoiding social meals due to medication schedules), and generates affective distress. The PPDS provides an empirical bridge within this model, capturing the psychological fallout induced by biological treatments.

Burden of Treatment Theory (BoTT)

Developed by Carl R. May and colleagues, the Burden of Treatment Theory structuralizes how the structural and functional demands of healthcare work interact with a patient’s personal capacity. BoTT conceptualizes patients as active agents who must mobilize cognitive, physical, emotional, and social resources to enact the “work” prescribed by healthcare systems—such as attending medical appointments, monitoring vital signs, and managing complex pharmacotherapies. When the cumulative demands of treatment surpass the patient’s functional or emotional capacity, treatment burden ensues. This imbalance induces structural distress, treatment fatigue, and eventual disengagement. The PPDS precisely operationalizes the affective breakdown that occurs when the cognitive and emotional labor demanded by polypharmacy exhausts a patient’s coping reserves.

Leventhal’s Common-Sense Model of Self-Regulation (CSM)

Howard Leventhal’s Common-Sense Model of Self-Regulation explains how individuals process health threats through parallel cognitive and emotional processing pathways. When confronted with illness, patients construct implicit cognitive illness representations (identity, cause, timeline, consequences, and controllability) while concurrently generating emotional representations (fear, anxiety, distress). Within this framework, medications do not function merely as passive remedies; they act as tangible, concrete cues that continuously reinforce the cognitive representation of the illness as severe, chronic, and incurable. Simultaneously, the complexity and perceived risks of the medications generate distinct emotional representations: fear of toxicities, anxiety over schedules, and frustration with physical side effects. The PPDS acts as a standardized metric of the emotional representation pathway within the CSM, quantifying the exact affective strain triggered by the self-regulation of multimorbidity through multi-agent pharmacotherapy.

Validity

The psychometric validation of the Polypharmacy-Related Psychological Distress Scale adhered to rigorous methodological standards, including the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) guidelines and best-practice frameworks for health measurement scale development.

Content and Face Validity

Content validity was established through a structured multi-round Delphi method involving an expert multidisciplinary panel comprising geriatricians, clinical pharmacologists, behavioral psychologists, and geriatric nursing specialists. The panel evaluated an initial item pool across dimensions of clinical relevance, conceptual clarity, domain representativeness, and wording precision. Quantification of expert consensus revealed robust validity metrics:

• Item-Level Content Validity Index (I-CVI): Ranged from 0.82 to 0.93 across the final retained items, substantially exceeding the conventional psychometric threshold of 0.78 recommended by Polit and Beck.
• Scale-Level Content Validity Index (S-CVI/Ave): Achieved an average index of 0.89, well above the acceptable standard of 0.80, confirming that the scale comprehensively captures the polypharmacy distress domain without extraneous conceptual clutter.
• Face Validity: To verify that the scale possessed linguistic lucidity and emotional resonance for the target population, qualitative cognitive interviews were conducted with older multimorbid patients experiencing polypharmacy. This debriefing process led to refined wording, eliminating clinical jargon and ensuring that items accurately tapped subjective distress.

Concurrent and Convergent Validity

Concurrent and convergent validity were evaluated by examining bivariate Pearson correlation coefficients between the PPDS and the Patient Health Questionnaire-4 (PHQ-4), a well-validated ultra-brief screener for generalized anxiety and major depression. In the validation cohort of 97 participants, the PPDS demonstrated a statistically significant, moderate positive correlation with the PHQ-4 ($r = 0.444, p < 0.001$).

From a psychometric perspective, this moderate correlation coefficient is conceptually optimal. If the correlation between the PPDS and the PHQ-4 had been excessively high ($r > 0.70$), it would have indicated severe multicollinearity, suggesting that the PPDS merely duplicated general negative affectivity or non-specific depressive-anxious distress. Conversely, a weak or non-significant correlation ($r < 0.20$) would have signaled a failure to capture core distress constructs. The observed value of$r = 0.444$ confirms that while polypharmacy distress is inherently linked to broader psychological vulnerability, it captures a distinct, domain-specific variance directly linked to pharmacotherapeutic burden.

Reliability

Evaluating internal consistency reliability within an ultra-brief instrument (four items) requires careful analytical consideration. Classic psychometric formulas, such as Cronbach’s alpha ($\alpha$), are mathematically dependent on the total number of items ($k$); holding average inter-item correlation constant, fewer items inevitably depress alpha values. Despite this constraint, the PPDS demonstrated strong reliability parameters across both classic and modern test theory frameworks:

• Cronbach’s Alpha ($\alpha$): The scale achieved a standardized alpha coefficient of 0.790. This sits comfortably within the widely accepted benchmark range of 0.70 to 0.85, confirming adequate inter-item relatedness without redundant item paraphrasing.
• McDonald’s Omega ($\omega$): Because Cronbach’s alpha relies on the often-violated assumption of essential tau-equivalence (equal factor loadings across all items), McDonald’s composite reliability omega was calculated. The PPDS demonstrated an omega coefficient of 0.937. This exceptionally high coefficient demonstrates superior latent construct reliability and confirms that the items function congruently in reflecting the single underlying latent trait.

During item analysis, one item evaluating anticipatory anxiety regarding medication precautions exhibited a marginally lower item-rest correlation relative to items assessing direct daily scheduling distress. However, the psychometric team made the theoretically grounded decision to retain this item. Removing it would have mathematically elevated Cronbach’s alpha slightly, but it would have compromised content validity by stripping away the critical psychological dimension of anticipatory fear and side-effect vigilance. This decision underscores best psychometric practices, balancing statistical optimization with broad theoretical construct fidelity.

Factor Analysis

The underlying latent dimensionality of the PPDS was investigated using Confirmatory Factor Analysis (CFA) to empirically validate the theoretically hypothesized unidimensional structure.

Model Fit Indices

Given the parsimonious four-item design, a single-factor model was specified where all four observed variables loaded onto a solitary latent construct of polypharmacy-related psychological distress. Maximum Likelihood estimation was employed, and model evaluation followed strict cutoff criteria established by Hu and Bentler (1999) and Brown (2015):

• Comparative Fit Index (CFI): 0.986 (exceeding the standard $ge 0.95$ threshold for excellent model fit).
• Tucker-Lewis Index (TLI): 0.987 (exceeding the standard $ge 0.95$ threshold for superior model fit).
• Standardized Root Mean Square Residual (SRMR): 0.040 (well below the $le 0.08$ threshold, indicating minimal residual discrepancy).
• Root Mean Square Error of Approximation (RMSEA): 0.060 (falling within the acceptable $le 0.06$ to $0.08$ range, indicating minimal specification error).

Standardized Factor Loadings

All four items exhibited strong, statistically significant standardized factor loadings ($lambda$) onto the single latent factor, ranging from 0.65 to 0.80 ($p < 0.001$). These loadings confirm t\hat each item contributes substantive unique variance ($R^2 = 0.42$ to $0.64$) to the latent continuum of polypharmacy distress. The absence of cross-loadings or significant correlated residual errors affirmed that a multidimensional structure was neither theoretically indicated nor empirically warranted.

Instrument / Measurement Tool

The operational specifications of the Polypharmacy-Related Psychological Distress Scale are structured as follows:

• Test Type: Patient-Reported Outcome Measure (PROM); brief self-report psychological screening questionnaire.
• Target Population: Adult and geriatric patients managing chronic multimorbidity who are concurrently prescribed multiple medications (typically $ge 5$ active pharmacotherapies).
• Target Age Group: Adults and older adults (primary validation sample centered on ages 60 to 79 years).
• Item Count: 4 items.
• Format & Administration: Paper-and-pencil questionnaire, clinician-administered interview, or secure digital electronic survey (via tablet or patient portal). Self-administered or assisted for patients with sensory/motor impairments.
• Estimated Completion Time: 1 to 2 minutes, ensuring zero administrative fatigue in busy healthcare environments.
• Response Scale: Likert-type response scale.
• Scoring Methodology: Total score is calculated by summing the numerical ratings across all 4 items. In the foundational validation trial, observed total scores ranged from 4 to 18. Higher scores indicate greater levels of polypharmacy-related psychological distress.
• Normative Reference Values: In the original validation cohort of older adults with polypharmacy ($N = 91$ complete cases), the mean total score was 11.9 with a standard deviation ($SD$) of 3.0.

Permissions & Fee and Test Year

The Polypharmacy-Related Psychological Distress Scale was formally published in 2025 in the peer-reviewed journal Behavioral Sciences (MDPI). The development and empirical validation study was led by researchers from Fudan University, Shanghai, China.

Licensing and Academic Access: Although the parent journal article is published under an open-access framework, the proprietary questionnaire items, official operational scoring rubrics, and translated linguistic variants remain under the copyright of the original authors. For academic research, non-commercial clinical trials, or hospital quality improvement initiatives, researchers and clinicians must contact the corresponding author, Dr. Cheng Cheng ([email protected]), to obtain formal permission and the official clinical instrument. Commercial applications, integration into proprietary electronic health record (EHR) software suites, or pharmaceutical industry-sponsored studies require explicit contractual authorization from the copyright holders.

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Items of the Scale