This population-based study aimed to investigate the prevalence and determinants of polypharmacy in a less developed region in southwestern Iran. The prevalence of depressive disorders during the last 12 months was estimated at 19.4%. Polypharmacy among patients with a recent history of DD was about 22%, which is two times higher than the prevalence in participants without such history. This study revealed that gender, ethnicity, physical activity, being overweight, SES, cigarette and tobacco smoking, and the presence of multimorbidity were independently associated with polypharmacy. After excluding the cardiovascular system drugs class, drugs related to the nervous system, the genitourinary system, and the alimentary tract and metabolism were the most common drug classes used by men, women, and elderly people, respectively. Consumption of both non-selective monoamine reuptake inhibitors and selective serotonin reuptake inhibitors among men was around three times more prevalent than that in women.
Although studying polypharmacy needs to separate its necessary type from the inappropriate forms, we know that polypharmacy, in a considerable share, is an indication of inappropriate or avoidable medication use, or some possible malpractices in the drug prescription [1, 21, 22]. Moreover, it may be partly a result of the unavailability of the combined drugs recently designed and approved . On the other hand, regardless of its appropriateness, polypharmacy is a leading cause of non-adherence to the medication therapy . Non-adherence to antidepressants is one of the challenging issues in the management of DDs, as it may complicate the psychopharmacotherapy and lead to a higher chance of relapse .
In line with the previous evidence, in this study the prevalence of polypharmacy among patients with DD was higher than that in participants without a recent history of DD . Some authors have argued that this higher prevalence is fully explained by the higher risk of comorbidities among patients with depression , but others have shown that even after adjustment for comorbidities the chance of polypharmacy in patients with DD is higher than that in patients without DD . In this study, the prevalence of polypharmacy among patients with both multimorbidity and history of DD was about 23% compared to about 14% among multimorbid patients without a history of DD. It may be a result of the health-seeking and medication utilization behaviors of patients that their DD has been diagnosed in a society without any active specialized psychiatric clinic. We also showed that after adjustment for age and gender, having a recent history of DD increases the prevalence of polypharmacy by more than 22 times. Accordingly, psychiatrists should be aware of this huge higher chance of polypharmacy among younger females with a recent history of DD and consider combination or more simple medication regimes, as well as deprescribing and other approaches to reduce and prevent polypharmacy among them .
This study revealed that the prevalence of polypharmacy is higher in women. A nationwide study from Sweden has shown that psychiatric polypharmacy among women was higher than men . Other studies have shown that the prevalence of polypharmacy among women, regardless of their status regarding depression, is higher than men . It may be a result of their healthcare-seeking behaviors such as their higher rates of adherence to the medication therapy and self-medication . It may also be a result of higher rates of multiple episodes or persistent DD among women compared to men.
Patients with Fars ethnicity have a higher prevalence of polypharmacy compared with others. Previous studies have shown that minorities and deprived subpopulations experienced higher rates of polypharmacy. It may be a result of their less access to and utilization of healthcare services such as pharmacy, and their less adherence to medication therapy.
Patients with the highest SES have a higher prevalence of polypharmacy. Although healthcare services are provided by the public sector in the study setting as specialized services are not available in this setting, higher SES may result in higher utilization of specialized services available in neighboring cities while in other SES a higher chance of untreated DD is probable. They may have a higher rate of adherence to the medication therapy or may use more OTC drugs such as vitamins, and also, they may be more affected by the direct-to-consumer (DTC) marketing because of the affordability of drugs not covered by insurance.
According to the study findings, low physical activity, unhealthy overweight, and tobacco smoking increase the prevalence of polypharmacy among patients with a history of DD. Such patients may have more inappropriate health-related behaviors and a probable lower adherence to prescribed therapies. Besides, these factors are risk factors for several chronic diseases. These chronic diseases their selves could lead to increased risk of development of depressive disorder or even deterioration of the severity of the already existing depressive disorder and therefore higher rate of polypharmacy[28, 29]. Although we adjusted for multimorbidity, as the number of comorbidities, we were unable to adjust for the severity of patients’ comorbidities. Therefore, this finding may be a residual confounding effect of the patients’ comorbidities. In the case of unhealthy overweight, it may be evidence of an undiagnosed symptomatic pathological mechanism that results in more medication use.
We showed that more than 55% of women with a history of DD were using the genitourinary system drugs class compared with less than 2% in men. A study from Colombia has reported that more than 50% of women older than 40 years were suffering from the genitourinary syndrome of menopause . Sundbom et. al.  have shown that among women with DD, drugs related to the genitourinary system were the 3rd common prescribed drug class. Psychiatrists may also need to consider asking about genitourinary diseases from female patients and adopt the therapeutic approaches that they chose. It may be improving the patients’ medication adherence and consequently decrease the rate of relapse.
Among men, the prevalence of use of almost all of the drug classes was 1.5 to 4 times lower than women, except for the nervous system drug class. Lower drug utilization among men is consistent with previous reports from other regions. However, it may be evidence of medication underuse among men. In case of a similar rate of utilization of the nervous system drugs class, considering a significantly lower rate of medication underuse among men compared with women, it may be a piece of evidence that in this setting men who are suffering from DD may also be suffering from other nervous system diseases such as epilepsy, neurodegenerative diseases, etc. that are more common in males . Further studies to investigate this issue are recommended.
Surprisingly, the prevalence of using antidepressants was higher among men compared with women. It may be a result of differential approaches preferred by the psychiatrists or the patients themselves to manage the DD in males and females . It may also be a result of a higher share of milder disorders in females .
The study findings showed that the prevalence of prescribing/utilization of both non-selective monoamine reuptake inhibitors (or Tricyclic antidepressants (TCAs)), and selective serotonin reuptake inhibitors (SSRI) were similar. A study from England reported a completely different pattern as more than 85% of patients were only on SSRI . This finding may be an indication of malpractice, a probable high rate of severe DD, or a different pattern of the effectiveness of available SSRIs in our setting, as SSRIs are typically used as the first-line psychopharmacotherapy to manage DD . A similar result has been reported from Germany . However, such a high rate of use of TCAs leads to a higher rate of drug side effects and consequently lower adherence to medication therapy or a higher rate of polypharmacy . Further studies on the patterns of prescription and utilization of antidepressants are needed.
This study used population-based but cross-sectional data. We were not able to determine the temporality of the polypharmacy and time-dependent variables, such as unhealthy overweight, that we identified as independent determinants of polypharmacy. Also, we were unable to investigate the effects of untreated or relapsed depression on polypharmacy. Another limitation of the study was our age-restricted sample excluding populations younger than 40 years old. Furthermore, this cross-sectional nature of the study limited us for the cause-effect analyses and we were not able to determine whether this is the depressive disorder that led to higher prevalence of polypharmacy among those with a medical disorder for example diabetes mellitus or conversely, it is the diabetes that is responsible for use of more medications among participants with recent depressive disorder. Besides, a high number of diseases has been included in the Pars Cohort Study database and there were small number of patients with some of these underlying diseases; accordingly, this issue limited us from including having different diseases in the multivariate analysis and the interaction between having recent depressive disorder and other diseases was not assessed in our main modelling. However, we designed Fig. 2 to depict an overview of the association of depression and polypharmacy prevalence among patients with different medical diseases.