Study Links Age and Comorbidities to Polypharmacy in Patients With Mental Illness

Hospitalized patients with psychiatric disorders accumulate nonpsychotropic medications for physical health conditions at a rate closely tied to their age and number of comorbidities—not their psychiatric diagnosis—according to a cross-sectional study published in Medicine.¹

Researchers led by Yoriyasu Uju, MD, and Tetsuto Kanzaki, PhD, of the National Kohnodai Medical Center and Chiba University in Japan, analyzed prescribing data from 250 hospitalized patients treated between April 2015 and March 2016. Although psychotropic medication counts remained stable across age groups and comorbidity levels, nonpsychotropic prescriptions rose sharply with both.¹

Study Design and Patient Population

The study drew on electronic medical records from the Psychiatry Department at National Kohnodai Medical Center, part of the Japan Institute for Health Security. It included 250 hospitalized patients (104 male, 146 female) with a mean age of 43.9 years, ranging from 13 to 87 years.¹

The largest diagnostic group was schizophrenia, acute and transient psychotic disorders, and schizoaffective disorders (F20, F23, F25), accounting for 150 patients (53.0%), followed by bipolar affective disorder (F31, 24 patients, 8.48%) and depressive episode or recurrent depressive disorder (F32, F33, 18 patients, 6.36%). The remaining 91 patients (32.1%) had other diagnoses, including epilepsy, developmental disorders, stimulant psychosis, attention-deficit/hyperactivity disorder (ADHD), or somatoform disorders.¹

Polypharmacy was defined as continuous use of 5 or more medications for at least 1 month, excluding OTC drugs, complementary medicines, and supplements. Of the 250 patients, 107 met that threshold and 143 did not. Patients with polypharmacy were older (mean age, 51.9±16.1 years) than those without (37.9±16.0 years) and had a higher mean body mass index (24.3±5.40 kg/m2 vs 22.3±5.43 kg/m2).¹

Nonpsychotropic Drugs Accounted for Nearly Half

Study participants were prescribed a total of 619 psychotropic medications and 486 non-psychotropic medications. Antipsychotics accounted for 47.8% of all psychotropic drugs (34.1% atypical, 13.7% typical), followed by antianxiety medications and hypnotics (23.9%), mood stabilizers (15.0%), anticonvulsants (5.70%), antidepressants (5.01%), antidementia agents (0.808%), and ADHD medications (0.485%).¹

Among nonpsychotropic drugs, medications for digestive disorders represented 50.2% of the total, and laxatives alone accounted for 40.0% of all nonpsychotropic prescriptions, or roughly 80% of the digestive disorder category. Cardiovascular medications (10.9%), antidiabetic agents (6.17%), and antidyslipidemic agents (5.97%) were the next most common classes.¹

Excluding digestive medications, drugs for cardiovascular disease, diabetes, and dyslipidemia together accounted for 46.3% of nonpsychotropic prescriptions. Hypertension, dyslipidemia, and type 2 diabetes were diagnosed in 23.7%, 15.2%, and 9.49% of patients, respectively, and together were present in 48.4% of the study population.¹

Age and Comorbidities, Not Diagnosis, Linked to Polypharmacy

In logistic regression analysis, age range (per 10-year increase) and number of comorbidities were the only variables significantly associated with polypharmacy. The odds ratio for age was 1.66 (95% CI, 1.39-1.97; P < .001), and for comorbidities, 2.04 (95% CI, 1.58-2.63; P < .001). Sex, number of days admitted, and number of psychiatric diagnoses showed no significant association with polypharmacy.¹

The mean number of nonpsychotropic prescriptions rose from 0.83 in patients aged 10 to 19 years to 5.80 in patients 80 years or older (linear regression coefficient [b] = 0.65; P = .0009). A similar pattern emerged by comorbidity count: patients with no comorbidities averaged 0.84 nonpsychotropic prescriptions, compared with 6.57 among those with 5 or more comorbidities (b = 0.91; P = .0002).¹

The mean number of psychotropic medications, by contrast, did not increase significantly with age (b = 0.04; P = .5899) or comorbidity count (b = 0.04; P = .6608). The researchers found the same divergence when they restricted the analysis to the 150 patients with schizophrenia, and the associations held in sensitivity analyses that excluded adolescent patients and in analyses stratified by sex.¹

The authors proposed that psychotropic regimens are typically established early in treatment and left largely unchanged once effective, and nonpsychotropic medications accumulate over time as patients develop additional physical illnesses such as cardiovascular disease, diabetes, or dyslipidemia. They linked the high volume of laxative use to antipsychotic-induced constipation, writing that its "predominant use was a major driver of the increased nonpsychotropic medication burden observed in this study."¹

Limitations and Broader Context

The authors noted several limitations: all participants were hospitalized, which may not reflect outpatient prescribing patterns; the study could not confirm whether patients actually took medications as prescribed; and subgroup sizes for bipolar affective disorder and depressive disorders were too small for separate analysis. They concluded that while guidelines exist for antipsychotic polypharmacy, "research on polypharmacy involving nonpsychotropic medications in these patients remains limited," calling their findings "an important first step" toward closing that gap.¹

Other research on psychiatric polypharmacy points to similar themes. A 2022 longitudinal study of 320 patients hospitalized in Zurich for schizophrenia or depression found that patients received an average of 4.50±2.68 total medications and that polypharmacy, present in 85% of that cohort, produced 2 to 3 times more severe adverse reactions than monotherapy without an offsetting efficacy benefit.²

A separate cross-sectional study of 544 chronically ill patients in Flanders, Belgium, published in Preventing Chronic Disease, found that 54.9% of participants met the threshold for polypharmacy and that polypharmacy was associated with significantly worse physical health-related quality of life (EQ-5D-5L index, 0.60 vs 0.69; P < .001), though not with mental health outcomes.³

What It Means for Pharmacists

The findings point pharmacists toward a specific target for medication review. The buildup of nonpsychotropic drugs, particularly laxatives, in older patients with psychiatric disorders who carry multiple physical comorbidities. Because laxative use tracked closely with the antipsychotic-induced constipation described in the study, reviews that address bowel regimens alongside cardiovascular and metabolic prescribing may offer a concrete way to trim unnecessary drug burden without disrupting psychiatric treatment.

A 2013 review in Mens Sana Monographs described the SAIL approach to managing psychiatric polypharmacy—keeping regimens Simple, tracking Adverse effects, prescribing only for clear Indications, and maintaining a complete List of medications—as one framework clinicians and pharmacists can use to review complex regimens without abandoning treatments patients need.⁴

REFERENCES

1. Uju Y, Kanzaki T, Hosoi R, Mimori S, Takizawa T, Hayakawa T. Patterns of non-psychotropic medication use and polypharmacy in patients with psychiatric disorders: A cross-sectional study on the association with age and physical comorbidity. Medicine (Baltimore). 2026;105(35):e50432. doi:10.1097/MD.0000000000050432

2. Stassen HH, Bachmann S, Bridler R, et al. Detailing the effects of polypharmacy in psychiatry: longitudinal study of 320 patients hospitalized for depression or schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2022;272(4):603-619. doi:10.1007/s00406-021-01358-5

3. Van Wilder L, Devleesschauwer B, Clays E, Pype P, Vandepitte S, De Smedt D. Polypharmacy and Health-Related Quality of Life/Psychological Distress Among Patients With Chronic Disease. Prev Chronic Dis. 2022;19:E50. Published 2022 Aug 18. doi:10.5888/pcd19.220062

4. Kukreja S, Kalra G, Shah N, Shrivastava A. Polypharmacy in psychiatry: a review. Mens Sana Monogr. 2013;11(1):82-99. doi:10.4103/0973-1229.104497