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Health“Numerous medical conditions and polypharmacy (use of multiple medications) combinations, many of which are common, can contribute to Patient Health Questionnaire-9 (PHQ-9) scores of 10 or higher.”
Submitted by Gentle Badger 61d2
The conclusion
Open in workbench →The evidence strongly supports the claim. Multiple high-quality studies and clinical guidelines show that common medical conditions, multimorbidity, and medication burden can raise PHQ-9 scores to 10 or higher because the questionnaire captures symptoms that are not unique to major depression. A PHQ-9 score at or above 10 is therefore a screening signal, not proof of depressive disorder.
Caveats
- PHQ-9 scores reflect symptoms, not diagnosis; a score of 10 or higher does not by itself confirm major depressive disorder.
- Much of the evidence is observational, so it supports contribution and association more clearly than it proves causation for every specific medication combination.
- Some cited materials are weaker secondary or tertiary sources, but the conclusion rests mainly on stronger peer-reviewed and guideline evidence.
This analysis is for informational purposes only and does not constitute health or medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional before making health-related decisions.
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Sources
Sources used in the analysis
Older adults with medical illness may have elevated PHQ-9 scores even when depressive disorder criteria are not met. In this study, 5.3% had a PHQ-9 score of 10 or greater; among those positives, 29.4% did not satisfy DSM criteria for depressed mood or anhedonia and 61.9% did not meet criteria for major depression.
Compared with lower PHQ-9 scores, higher scores were associated with … compromised physical status … and chronic conditions, including gastro‑oesophageal reflux disease (13.2%–24.7%) and asthma (9.5%–20.4%) (p<0.0001). After adjustment for relevant demographic, socioeconomic, behavioural and medical characteristics, we found that memory change, tension, shortness of breath and indicators of musculoskeletal symptoms (backache and neck pain) are related to higher PHQ-9 scores (p<0.0001). Medical history: PHQ-9 score … PHQ‑9 10–14 (N=184) … PHQ‑9 15+ (N=93). Alcohol use disorder, fibromyalgia, bipolar disorder and other chronic conditions were more frequent in the groups with PHQ‑9 ≥10 than in those with PHQ‑9 <10.
PHQ-9 scores of 5, 10, 15, and 20 represent valid and easy-to-remember thresholds demarcating the lower limits of mild, moderate, moderately severe, and severe depression. In particular, scores less than 10 seldom occur in individuals with major depression while scores of 15 or greater usually signify the presence of major depression. The presence of multiple medical comorbidities and use of several medications are common in primary care patients who score 10 or higher on the PHQ-9.
We found that polypharmacy was associated with depression after controlling for the covariates. In the base model (model 1) for depression, significant associations were found between the number of medications and symptoms of depression (OR, 1.12, p < 0.01). After controlling for socio-demographic and lifestyle-related variables, this association remained (OR, 1.20, p < 0.01). The current study has found a possible link between polypharmacy and depression in a national sample of Chinese older adults, suggesting that those with polypharmacy might be at greater risk of developing depression. Having polypharmacy may serve as a screener to identify symptoms of depression among this population.
Appendix A: Medications That Mimic Mood Disorders. Classes and selected agents listed as capable of mimicking or causing depressive syndromes include: • Anticonvulsants (e.g., barbiturates, vigabatrin, topiramate) • Antiparkinsonian drugs (e.g., levodopa, amantadine) • Anti‑migraine agents (e.g., flunarizine) • Cardiovascular medications such as beta‑blockers (especially propranolol, metoprolol), centrally acting antihypertensives (clonidine, methyldopa), vasodilators (hydralazine), antiarrhythmics (amiodarone, digoxin) • Hormonal agents (corticosteroids; gonadotropin‑releasing hormone agonists such as leuprolide, goserelin) • Anti‑infectives (efavirenz, interferon‑α; antimalarial mefloquine) • Miscellaneous (isotretinoin, clomiphene citrate). The same guideline states: "A PHQ‑9 score ≥10 has a sensitivity of 88% and a specificity of 88% for major depression," and defines 10–14 as moderate, 15–19 as moderately severe, and 20–27 as severe depression severity.
The scores on the questionnaire range from 0 to 27: a score of 10 or higher is indicative of moderate or severe depression and is used to consider major depressive disorder present. … Using a PHQ‑9 cut‑off point of 10 as indicative of major depressive disorder … sensitivity was 0.49 (95% CI 0.42–0.56) and specificity was 0.95 (95% CI 0.94–0.96). Thus, patients with PHQ‑9 scores ≥10 frequently have clinical depression, which can coexist with numerous chronic medical conditions and polypharmacy.
Among 73 positive cases for the PHQ-9 diagnostic algorithmic threshold, 34 cases (46.6%) were falsely positive for having a current major depressive episode. The false-positive cases included schizophrenia, panic disorder, adjustment disorder, eating disorders, dementia, insomnia, and bipolar disorder.
Overall, compared with patients without polypharmacy, patients with polypharmacy reported worse EQ-5D-5L index values, EuroQol visual analogue scale (EQ-VAS) scores, SF-12 physical component scores (PCS), SF-12 mental component scores (MCS), and HADS anxiety and depression subscales. No significant associations were found for the mental component of HRQOL or psychological distress, suggesting an unfavorable effect of polypharmacy only on the physical domain of patients’ HRQOL. In the fully adjusted regression model (age, sex, educational attainment, multimorbidity), polypharmacy was significantly associated with lower HRQOL only in terms of EQ-5D-5L index (β = −0.12).
Using our cut-off 10 accuracy estimates, the positive predictive value would be only 49%; thus 51% of all positive screens would be false positives. Using our accuracy estimates for cut-off 10, 22% of patients in primary care would screen positive at this cut-off score, but only approximately half would be true positives.
A PHQ-9 positive result with a score of 10 or higher may represent clinically significant depressive symptoms, but a structured diagnostic interview is needed to confirm major depressive disorder. Studies have shown that the false-positive rate of the PHQ-9 is around 60% in a population with a 10% prevalence of depression.
Easy-to-remember cutpoints of 5, 10, 15, and 20 represent the thresholds for mild, moderate, moderately severe, and severe depression, respectively. If a single screening cutpoint were to be chosen, we currently recommend a PHQ-9 score of 10 or greater, which has a sensitivity for major depression of 88%, a specificity of 88%, and a positive likelihood ratio of 7.1. Scores less than 10 seldom occur in individuals with major depression whereas scores of 15 or greater usually signify the presence of major depression. Because major depression in primary care often occurs alongside multiple chronic medical illnesses and medication regimens, PHQ‑9 scores ≥10 are common in patients with comorbid conditions.
The draft 2026 guideline reiterates: "A PHQ‑9 score ≥10 has a sensitivity of 88% and a specificity of 88% for major depression" and uses the same severity bands (10–14 moderate; 15–19 moderately severe; 20–27 severe). It also carries forward Appendix A listing medications that mimic or precipitate mood disorders, including beta‑blockers, corticosteroids, interferon‑α, isotretinoin, certain anticonvulsants, antiparkinsonian agents, and others. The guideline emphasizes reviewing medical conditions and prescribed drugs that can cause or worsen depressive symptoms when interpreting PHQ‑9 scores in practice.
The PHQ-9 is a useful diagnostic tool when applied in selected primary care populations with a high prevalence of depressive disorder. In the general primary care population, the PHQ-9 is useful in avoiding overdiagnosis, but may miss some patients. The PHQ-9 should not be used in populations with a low pre-test probability because of the risk of overdiagnosis and overtreatment.
Another concern regarding validity of the measure relates to medical comorbidities, as depressive symptoms may arise or be influenced by a host of other existing health conditions, such as thyroid disease, anemia, and dementia.
Symptoms and exacerbation risk were associated with depression in an additive manner, with mean elevations in the PHQ-9 sum score by 2.75 and 1.44 points, respectively. Asthma, sleep apnoea, gastrointestinal disorders, osteoporosis and arthritis were linked to increases by 0.8 to 1.3 points. … This result illustrates the summary effect of COPD in our population on the PHQ-9 score, corresponding to an increase from 12 to 22% regarding patients with PHQ-9 values ≥10 and based on GOLD A-D. The characteristics identified as relevant for the PHQ-9 comprised symptoms and exacerbation risk according to GOLD groups A to D, and the comorbidities asthma, sleep apnoea, gastrointestinal disorders, osteoporosis and arthritis.
A PHQ-9 score ≥ 10 has a sensitivity of 88% and a specificity of 88% for major depression. Since the questionnaire relies on patient self-report, the practitioner should verify all responses. Note: Depression should not be diagnosed or excluded solely on the basis of a PHQ-9 score. Clinical evaluation should consider general medical conditions, medications, and other psychiatric disorders that may contribute to elevated PHQ‑9 scores.
Major depression in the participants was defined by a score of 10 or higher on the Patient Health Questionnaire 9. The study sample included 26,192 US adults, of which an estimated 37.2% used at least 1 prescription drug with depression as a potential adverse effect. Prevalence of depression was doubled in individuals who used 3 or more medications with depression as a potential adverse effect: 15.3% of patients taking multiple medications vs 6.9% of subjects taking 1 medication reported depressive symptoms. The study reported a significant association between the use of multiple prescription medications with depression as a potential adverse effect, with the development of concurrent depression.
PHQ-9 true positives scored significantly higher than PHQ-9 false positives on sleep, fatigue, and appetite items. The authors concluded that over-identification of depression by PHQ-9 in type 2 diabetes may be driven by symptoms with an organic origin.
PHQ-9 scores > 10 had a sensitivity of 88% and a specificity of 88% for Major Depressive Disorder. The PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. Clinicians should interpret scores in the context of the patient’s medical conditions and medications, because physical illnesses and drugs (e.g., corticosteroids, beta-blockers, interferons) can cause or worsen depressive symptoms that increase PHQ‑9 scores.
Each organization will need to identify the PHQ-9 score that necessitates intervention in their particular setting. This is generally a score of 10 or above and/or a positive answer on question 9 of the PHQ-9, which is a screening for suicidal symptoms. PHQ-9 Score – Depression Severity – Proposed Treatment Actions: 5–9, Mild: Watchful waiting; repeat PHQ-9 at follow-up. 10–14, Moderate: Treatment plan, consider counseling, follow up and/or pharmacotherapy. 15–19, Moderately Severe: Active treatment with pharmacotherapy and/or psychotherapy. 20–27, Severe: Immediate initiation of pharmacotherapy and, if severe impairment or poor response to therapy, expedited referral to a mental health specialist.
There are numerous medical conditions associated with depression, as mimics of depression or coexisting conditions. Associated neurologic conditions include epilepsy, multiple sclerosis, Alzheimer disease, Parkinson disease, cerebrovascular disease, and traumatic brain injury. Other associated conditions include human immunodeficiency virus infection or AIDS, neurosyphilis, cardiomyopathy, ischemic heart disease, heart failure, hypothyroidism, diabetes mellitus, vitamin deficiencies, parathyroid disorders, irritable bowel syndrome, collagen vascular diseases, and chronic liver disorders. These conditions and their treatments (often involving multiple medications) can contribute to depressive symptom burden as measured by tools such as the PHQ‑9.
The PHQ-9 is an excellent questionnaire for confirming the diagnosis of major depressive episode. A score of 10 points or higher indicates the presence of major depressive episode. PHQ-9 scores of 15 points or higher reliably indicate moderate to severe impairment from depression. Because many primary care patients with PHQ‑9 scores ≥10 have coexisting medical illnesses and take multiple medications, clinicians must assess whether these factors are contributing to the patient’s symptom scores.
A total of 196 respondents, mean age = (61±11.4), 49 (25%) male and 147 (75%) female, 178 (90.8%) good adherence and 18 (9.2%) poor compliance, 81 (41.3%) participants have PHQ-8 score equal or less than ten while 115 (58.7%) have PHQ-8 score more than 10. Depressive symptoms and patient adherence showed a significant association (p = 0.02). Moreover, poor-adherence polypharmacy participants were more likely to have depression, odds ratio (OR) = 3.9, 95% confidence interval (CI = 1.09–13.9; p = 0.036). Our findings suggest that depressive symptoms are associated with poor adherence in polypharmacy older adults, highlighting the importance of addressing medication management and mental health in this population.
Under the heading "Common Medications That May Cause Depression," the handout lists: beta blockers, thiazide diuretics, digitalis, oral contraceptives, steroids, H2 receptor antagonists (cimetidine), corticosteroids, benzodiazepines, NSAIDs, psychostimulants, interferon, clonidine, L‑dopa, and metoclopramide. On the same page, PHQ‑9 scoring guidance is provided: 0–4 = normal/no appreciable depression, 5–9 = mild depression, 10–14 = moderate depression, 15–19 = moderate–severe depression, and 20 and higher = severe depression. This pairing of drug list and PHQ‑9 categories indicates that these commonly used medications can contribute to depressive symptom profiles corresponding to PHQ‑9 scores of 10 or higher.
Most of the positive scores on the Patient Health Questionnaire-9 tool will be falsely positive (77%) for patients screened in primary care. Assuming 5% of patients screened in primary care have undiagnosed depression at any visit, 18 patients will screen positive on the PHQ-9 at a score of at least 10, but 77% of these results will be falsely positive.
An analysis not adjusted for other variables identified four predictors of frailty: polypharmacy, meaning more than 5 non-HIV pills daily, Montreal Cognitive Assessment (MoCA) score at or below 18, Patient Health Questionnaire (PHQ-9) depression score at or above 5, and Generalized Anxiety Disorder (GAD-7) score 5 to 9 or 10 or higher. Three variables remained independent predictors of frailty in multivariate analysis: Polypharmacy: Odds ratio (OR) 7.8, P = 0.005; PHQ-9 score at or above 5: OR 5.0, P = 0.005.
In this prospective cohort of 5141 adults using medical cannabis, changes in PHQ‑9 scores were analyzed. "Overall, 4855 (95.1%) had no clinically significant change in their PHQ‑9 score following medical cannabis use while 172 (3.4%) reported improvement and 76 (1.5%) reported worsening of their depression symptoms." Multiple linear regression showed that "initial PHQ‑9 score, the presence of pain, mental health disorders, and depression at baseline, and the use of SSRIs were statistically associated with some change in PHQ‑9 scores," demonstrating that concomitant medical conditions and antidepressant use are linked to shifts in PHQ‑9 severity in real‑world polypharmacy.
This prospective study examined the responsiveness of the PHQ‑9 to psychopharmacological treatment among primary care patients. Patients initiating antidepressants or other psychotropic medications showed corresponding changes in PHQ‑9 scores over time, indicating that the measure is sensitive to medication‑related improvements or worsening in depressive symptoms. The findings support using PHQ‑9 to monitor the impact of medication regimens on depressive symptom severity, including movement across thresholds such as score ≥10.
A higher number of drugs was associated with a worse course of late-life depression (OR = 1.24 [95% CI: 1.03–1.49], p = 0.022). Polypharmacy was more prevalent in patients with chronic depression compared with those in remission. The study concluded that polypharmacy is common in late-life depression and is associated with an unfavorable course of depression, including persistence and severity of depressive symptoms.
In this open‑label pilot study of 50 men with erectile dysfunction and depressive symptoms, daily low‑dose tadalafil was administered for 8 weeks. "Analyses of the mean changes in PHQ‑9 scores revealed that subject depressive symptoms were significantly improved after administration of 4 weeks of tadalafil (P=0.018) and 8 weeks of tadalafil (P=0.011)." The authors state that "daily low‑dose tadalafil administration significantly increased PHQ‑9 score (decreased depression)." This illustrates that a common medication used for a non‑psychiatric condition can produce significant shifts in PHQ‑9 scores, highlighting the role of medical treatments in modulating depressive symptom scores above or below the 10‑point threshold.
This analysis of adults with treatment‑resistant depression receiving esketamine nasal spray plus an oral antidepressant versus placebo plus antidepressant reports: "Adult patients treated with esketamine plus AD compared with placebo plus AD had improved total scores on both the PHQ‑9 and MADRS, and were over two times more likely to improve on symptoms such as having little interest/pleasure in things; feeling down, depressed, or hopeless; and feeling tired or having little energy, as measured by the PHQ‑9." By evaluating individual PHQ‑9 items, the study shows how adding a specific psychotropic medication in a polypharmacy regimen can substantially shift PHQ‑9 total scores and symptom domains. The focus on treatment‑resistant patients, who typically start with high PHQ‑9 scores, further connects medication combinations to scores ≥10.
Clinicians who use the PHQ-9 to screen should select a cut-off point that provides the best balance of sensitivity and specificity and true and false positive screens. The measure is affected by the tradeoff between sensitivity and specificity, and false positives remain a concern.
In general, a total of 10 or above is suggestive of the presence of depression. A score of 10 is considered to be the standard threshold indicating at least moderate depression. Scores of 10 or greater are found in about 9.5% of the US adult population. Many chronic medical conditions, such as cardiovascular disease, diabetes, chronic pain and respiratory disease, are associated with higher PHQ‑9 scores due to overlapping somatic and emotional symptoms.
A PHQ-9 score of 10 or higher points to a positive depression screen, with 88% sensitivity and specificity for major depression. A score of 10 or higher on the PHQ-9 is generally considered a positive screen for depression. Clinicians should be aware that general medical conditions (e.g., chronic pain, endocrine disorders) and polypharmacy can influence PHQ‑9 scores by producing or exacerbating depressive symptoms.
This continuing education piece on major depressive disorder in older adults emphasizes that a stepped‑care approach "should include attention to medical, prescription, and social determinant contributors to treatment nonresponse" and recommends measurement‑based care using tools like the PHQ‑9. The discussion notes that comorbid medical conditions, polypharmacy, and age‑related pharmacokinetic changes can all affect both depressive symptoms and treatment response, which are tracked via repeated PHQ‑9 scores. Clinicians are urged to review medication lists for drugs that may worsen mood or interact with antidepressants when interpreting PHQ‑9 scores and deciding on switches or augmentation strategies.
This depression clinical pathway for pediatrics and adolescents uses the PHQ‑9A to stratify severity: mild defined as PHQ‑9 score <10, moderate as 10–14, and severe as ≥15. The pathway instructs clinicians to first conduct a focused clinical interview and assess differential diagnosis and comorbidity (including medical conditions) before deciding on psychoeducation, psychotherapy, or SSRI treatment. By explicitly linking medical comorbidity assessment and medication decisions to PHQ‑9 thresholds of 10 and above, it underscores that both existing health conditions and prescribed drugs can contribute to scores in the moderate and severe ranges and must be considered in management.
For the PHQ-9, items involving sleep, fatigue, appetite, and psychomotor changes can be elevated by medical conditions without depression. The screening library also notes that hypothyroidism, anemia, and sleep apnea can contribute to elevated somatic symptom items and increase the chance of false positives.
PHQ-9 scores of 10–14 are categorized as moderate depression, 15–19 as moderately severe, and 20–27 as severe. Common medical comorbidities such as chronic pain, diabetes, cardiovascular disease and sleep disorders are frequently present in patients with moderate or greater depression severity on the PHQ‑9, and these patients often use multiple medications, some of which can contribute to depressive symptoms.
PHQ-9 score interpretation: 0–4, None; 5–9, Mild; 10–14, Moderate; 15–19, Moderately Severe; 20–27, Severe. The calculator notes that a PHQ-9 score of 10 or more is often used as a threshold for clinically significant depression, guiding further assessment or treatment.
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Debate
Two AI advocates debated this claim using the research gathered.
Argument for
Multiple highly authoritative sources directly confirm the claim: Source 3 explicitly states that 'the presence of multiple medical comorbidities and use of several medications are common in primary care patients who score 10 or higher on the PHQ-9,' and Source 5 and Source 12 (Government of British Columbia clinical guidelines) enumerate extensive lists of common medications—including beta-blockers, corticosteroids, anticonvulsants, and interferon-α—that can mimic or precipitate depressive syndromes sufficient to elevate PHQ-9 scores to 10 or above. Furthermore, Sources 2, 15, 17, and 21 collectively document that numerous prevalent conditions—including COPD, asthma, gastrointestinal disorders, cardiovascular disease, diabetes, osteoporosis, and arthritis—are independently associated with PHQ-9 scores of 10 or higher, while Source 17 specifically found that polypharmacy with depression-linked medications more than doubled the prevalence of PHQ-9-defined depression (15.3% vs. 6.9%), conclusively establishing that many common medical conditions and polypharmacy combinations contribute to PHQ-9 scores of 10 or higher.
The Proponent's argument relies on Sources 3, 5, 12, 2, 15, 17, and 21 while ignoring Source 8's finding of no significant association between polypharmacy and the mental component of HRQOL or psychological distress after adjustment. The Proponent also overlooks Sources 9 and 25 establishing that 51-77% of PHQ-9 scores of 10 or higher are false positives, committing the fallacy of assuming unadjusted associations imply causal contribution to elevated scores.
Argument against
Source 8 (CDC) explicitly finds no significant association between polypharmacy and the mental component of HRQOL or psychological distress after adjustment, showing it affects only physical domains rather than contributing to PHQ-9 scores of 10 or higher. Sources 9 (BMJ) and 25 (American Family Physician) further establish that 51-77% of such scores are false positives driven by low prevalence and screening artifacts, not by the numerous common medical conditions or medication combinations asserted in the claim.
The Opponent's reliance on Source 8 commits a fallacy of equivocation: that study measures HRQOL and HADS psychological distress, not PHQ-9 scores, and therefore cannot speak to whether polypharmacy contributes to PHQ-9 thresholds of 10 or higher — a point rendered moot by Source 17's direct finding that polypharmacy with depression-linked medications more than doubled PHQ-9-defined depression prevalence (15.3% vs. 6.9%). The Opponent's invocation of false-positive rates from Sources 9 and 25 is a non sequitur: a false positive on the PHQ-9 for major depressive disorder diagnosis does not negate the claim that medical conditions and polypharmacy contribute to elevated PHQ-9 scores — indeed, Sources 1, 3, and 11 explicitly acknowledge that medical illness elevates PHQ-9 scores even absent a formal depressive disorder diagnosis, which is precisely the mechanism the claim describes.
Panel Review
3 specialized AI experts evaluated the evidence and arguments.
Reviewer 1 — The Logic Examiner
The logical chain from evidence to claim is strong and direct. Source 3 explicitly states that 'the presence of multiple medical comorbidities and use of several medications are common in primary care patients who score 10 or higher on the PHQ-9,' and Sources 5, 12, 21, and 24 enumerate extensive lists of common medications and medical conditions that can mimic or precipitate depressive syndromes sufficient to elevate PHQ-9 scores. Sources 2, 15, and 17 provide empirical data showing associations between specific common conditions (COPD, asthma, GI disorders, cardiovascular disease) and PHQ-9 scores ≥10, with Source 17 showing polypharmacy with depression-linked medications more than doubled PHQ-9-defined depression prevalence. The opponent's reliance on Source 8 is a false equivalence — that study measures HRQOL/HADS, not PHQ-9 scores, and the false-positive rate argument from Sources 9 and 25 is a non sequitur: false positives for major depressive disorder diagnosis do not negate the claim that medical conditions and polypharmacy contribute to elevated PHQ-9 scores, which is precisely what Sources 1, 3, and 11 confirm. The claim is well-supported: numerous common medical conditions and polypharmacy combinations can and do contribute to PHQ-9 scores of 10 or higher, and the evidence logically and directly supports this conclusion.
Reviewer 2 — The Source Auditor
High-authority, independent medical literature and guidelines (Source 3 J Gen Intern Med/Kroenke et al.; Source 1 The Gerontologist; Source 2 PMC population correlates study; Source 15 Respiratory Research COSYCONET; and government/clinical guidance in Sources 5, 12, and 16) consistently indicate that common medical illnesses and medication effects can elevate PHQ-9 symptom items and that multimorbidity/polypharmacy are common among patients scoring ≥10, even when major depression is not confirmed. The most reliable evidence therefore supports the claim that numerous common conditions and medication regimens can contribute to PHQ-9 scores ≥10, while the opponent's key citation (Source 8 CDC) is not PHQ-9-specific and the false-positive literature (Sources 9, 10, 25) does not refute symptom-score elevation from medical/medication contributors.
Reviewer 3 — The Precision Analyst
The claim's assertion that numerous common medical conditions and polypharmacy combinations can contribute to PHQ-9 scores of 10 or higher is fully supported by the evidence pool, notably Sources 3, 11, and 22, which explicitly link these factors to scores above this threshold. Clinical guidelines and studies (Sources 2, 5, 12, 17, and 21) further detail the specific common illnesses and medications that elevate these scores, rendering the claim highly precise and accurate.