|Year : 2019 | Volume
| Issue : 4 | Page : 204-210
Antidepressant prescription patterns and associated factors among the elderly with psychiatric illnesses
Shu-Wen Cheng M.S 1, Hung-Yu Chan M.D., Ph.D 2
1 Department of Pharmacy, Taoyuan Psychiatric Center, Taoyuan, Taiwan
2 Superintendent Office, Taoyuan Psychiatric Center, Taoyuan; Department of Psychiatry, National Taiwan University Hospital and School of Medicine, National Taiwan University, Taipei, Taiwan
|Date of Submission||11-Aug-2019|
|Date of Decision||11-Sep-2019|
|Date of Acceptance||22-Sep-2019|
|Date of Web Publication||23-Dec-2019|
No.71, Long-show Street, 33058, Taoyuan
Source of Support: None, Conflict of Interest: None
Objectives: The prevalence of antidepressant prescriptions for elder patients with psychiatric illnesses is increasing over the world. No studies exist to focus on the prescription patterns and trend of antidepressant use for the elderly in psychiatric hospitals of Taiwan. Methods: In this retrospective study for all outpatients equal or over 65 years of age in a psychiatric hospital, we collected related study variables from the study hospital from 2006 to 2015. Reviewing data of the electronic medical information system, we extracted both patients' demographic data (information for sex, age, and insurance status) and their clinical variables (psychiatric diagnosis and prescriptions of antidepressants). Results: In this study, we found that the proportion of antidepressant prescriptions was increased at around 7.85% (from 39.79% in 2006 to 42.92% in 2015, p < 0.001). We also found that the proportions of some antidepressants (selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, norepinephrine–dopamine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants) were increased, but some antidepressants (tricyclic antidepressants [TCAs] as well as serotonin antagonist and reuptake inhibitors) were decreased over the study period. TCAs were decreased in their use from 2.52% to 1.72%. The logistic regression showed that female gender, younger age, affective disorders, and neurotic disorders were found to be associated with a higher chance of antidepressant prescriptions. Conclusion: The result of this study is similar to the conclusion of other previous studies. But the decreased trend of TCA prescriptions is different from that in other studies. Future research should focus on the treatment indications, associated factors, off-label use, adverse effects, and safety of antidepressants in the elderly population.
Keywords: citalopram, elder patients, geriatric patients, mirtazapine
|How to cite this article:|
Cheng SW, Chan HY. Antidepressant prescription patterns and associated factors among the elderly with psychiatric illnesses. Taiwan J Psychiatry 2019;33:204-10
|How to cite this URL:|
Cheng SW, Chan HY. Antidepressant prescription patterns and associated factors among the elderly with psychiatric illnesses. Taiwan J Psychiatry [serial online] 2019 [cited 2020 Jan 27];33:204-10. Available from: http://www.e-tjp.org/text.asp?2019/33/4/204/273865
| Introduction|| |
The prescription rates of antidepressants for the elder patients have been increasing in the recent decades ,,,,. Previous studies also showed that the elderly receive the most antidepressant prescriptions among all of age groups ,,. Tricyclic antidepressants (TCAs) are the earliest antidepressants used for the elderly. But the elderly are vulnerable to several TCA side effects, such as cardiac toxicity, seizure attacks, urinary difficulty, and sedation. Furthermore, TCA anticholinergic properties may impair the cognitive functions of patients with dementia. Therefore, several treatment guidelines suggest that TCAs have a low priority for geriatric patients in their antidepressant treatment .
Differing in TCAs, selective serotonin reuptake inhibitors (SSRIs) have less anticholinergic, antihistamine, and antiadrenergic side effect profiles, such as dry mouth, constipation, sedation, body weight gain, and cardiotoxicity. SSRIs may be a better choice in treating geriatric depression. But previous studies showed that some SSRIs are more suitable for elder patients with depression than other antidepressants. The study by Garrison and Levin showed that sertraline is a recommended antidepressant with the most prescription rate for the elderly . Other studies suggested that fluoxetine is not a good choice for the elderly with depression due to its long half-life with the risk of drug–drug interaction and central nervous stimulation profiles .
Several studies have investigated the prescription rates of antidepressants for elder patients. Soudry et al.'s 2-year cohort study  found that the prescription rates of antidepressants for French community people older than 65 years old have increased from 7.0% to 8.6%. They also found that the increased SSRI prescriptions are the principal factors . An Italian study also illustrated that the prescription rates of antidepressants have increased twice from 2000 to 2007 for the elderly, and that increased SSRI prescriptions and female patients are the major contributing findings . The prescription rates of antidepressants for the elderly have also increased from 7.36% to 9.39% during the period from 2004 to 2007 in New Zealand, and over 90% patients have received SSRIs or TCAs . Some studies have focused on the comparison between the community and institution population. The study of Harris et al. showed that the prevalence of antidepressant prescriptions for the elderly in England and Wales is much higher in the sample of institution (37.5%) than that in the community (10.3%) .
The claims data studies have also illustrated the similar results of increasing trend of antidepressant prescriptions for elder patients. The study by Chien et al. showed that the prevalence of antidepressant prescriptions for elder people has increased from 2.2% to 4.4% during the period from 1997 to 2004. They also found that the proportion of second-generation antidepressants (SSRIs or newer antidepressants) has increased from 51.5% to 68.1% during the study period .
In clinical practice, we sometimes can find that patients actually need psychoeducation or psychotherapy rather than antidepressant treatment to deal with their discomforts. But clinicians prescribe unnecessary antidepressants without providing appropriate psychological interventions. Therefore, the increased prescription rates of antidepressants for the elderly are not necessarily a good medical quality of care. Bobo et al.'s study showed that the proportion of antidepressants over prescription for the elderly is about 24% during the period from 2005 to 2012. Furthermore, they found that SSRIs are the most frequently (74%) prescribed antidepressants, and that mirtazapine is the second most .
In summary, most previous studies of the rates of antidepressants for the elderly in different countries showed that the trends are increasing. But no studies exist to focus on the population of psychiatric hospital. Many previous studies investigated the trend of antidepressant prescriptions only for short periods and not over 10 years. In this study at a psychiatric hospital, we carried out a 10-year period. We also intended to study the associated factors of antidepressant prescriptions for the elderly.
| Methods|| |
This study was conducted at Taoyuan Psychiatric Center (TYPC), a public, regional teaching hospital in northern Taiwan, providing service of 282 acute beds, 380 chronic beds, and 300 daycare beds. The hospital is one of the biggest psychiatric services for the elderly in Taiwan. TYPC provides various treatments for elder psychiatric patients, including (a) outpatient treatment more than 1,500 patient visits per month, (b) 50 daycare beds for the elderly, and (c) 30 acute beds for elder patients. The study proposal was approved by the hospital institutional review board, without the need of obtaining the signed informed consents from the study patients (protocol number = B20170801 and approval date = September 17, 2017).
Study design, study variables, and data extraction
This is a retrospective study for all outpatients equal or over 65 years old. We collected related study variables from the electronic medical information system from 2006 to 2015 at TYPC, where has an electronic medical information system established in January 2000. Data from this system are transformed into related database, referred to as the data “warehouse.” We extracted study data from the warehouse and created our analytic dataset with Statistical Package for the Social Sciences software version 20.0 for Windows (SPSS, Inc., Chicago, Illinois, USA), and Statistical Analysis System software version 9.3 (SAS institute Inc., Cary, North Carolina, USA). Reviewing the electronic medical information system, we extracted both patients' demographic data (such as sex and age) and clinical variables (psychiatric diagnosis and prescriptions of antidepressant). The psychiatric diagnosis was extracted only from the first diagnosis of the study patients. Antidepressants are classified with Anatomical Therapeutic Chemical (ATC) system of the World Health Organization (WHO). A study pharmacist with a more than 20-year experience in psychiatric research extracted the data. The corresponding author (HYC), a board-certificated psychiatrist, regularly supervised and discussed with the pharmacist (SWC) on the extraction study results.
The data of the antidepressants were examined and categorized into TCAs (imipramine, doxepin, and clomipramine), SSRIs (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, and escitalopram), serotonin–norepinephrine reuptake inhibitors (SNRIs; venlafaxine, milnacipran, and duloxetine), noradrenergic and specific serotonergic antidepressants (NaSSAs; mirtazapine), serotonin antagonist and reuptake inhibitors (SARIs; trazodone), norepinephrine–dopamine reuptake inhibitors (NDRIs; bupropion), and reversible inhibitors of monoamine oxidase A (RIMA; moclobemide). We also examined the demographic and clinical data to see if any underlying risk factors existed to be associated with the antidepressant prescriptions.
Due to the long study period of this study, different outpatient visits for each person may have different disease events. Patients with repeated prescriptions for the same diagnosis may have different symptom intensities and different outcomes during each outpatient visits. Therefore, we counted the prescription of each outpatient visit instead of each person in this study to calculate the factors associated with the antidepressant prescriptions.
Categorical variables were compared using Chi-square and Fisher's exact test, and continuous variables were compared using independent t-test. We also used Cochran–Armitage trend test to examine the time trend of antidepressant prescriptions. Multivariate logistic regression models were further tested for examining the risk factors of antidepressant prescriptions. We included covariates in the multivariate logistic regression model if we deemed them to be of clinical significance, such as age, gender, and diagnosis, or if they had a univariate p < 0.05. The coefficient of determination for the multivariate model was estimated using Nagelkerke pseudo R-squared. All results were expressed as means ± standard deviations (SDs).
We used SPSS and SAS for all statistical analysis in this study. The differences between the groups were considered significant if p < 0.05.
| Results|| |
There were 110,576 elder outpatient visits during the study period. A total of 47,360 visits had antidepressant prescriptions with the prescription rate of 42.83% (47,360/110,576). The mean age ± SD of the study samples was 75.28 ± 7.33 years, and the age of antidepressants used was 75.20 ± 7.13 years. The total items of antidepressant prescriptions were 56,108 with 1.18 (56,108/47,360) items of antidepressants in each prescription on average. We collected 8,468 elder outpatient visits with two or more antidepressant prescriptions at the same time with the percentage of antidepressants polypharmacy being 17.88% (8,468/47,360).
About the distribution of antidepressant prescriptions in the study population, SSRIs had the highest prescription rate (34.43%) among all antidepressants, follow by SARIs (31.55%) and NaSSAs (16.13%). In SSRIs, escitalopram had the highest prescription rate (11.83%) followed by sertraline (8.19%). TCAs were used in only 4.04%.
[Table 1] lists and compares patients' demographic data and baseline clinical characteristics of the participants who received and not received antidepressant drugs. Patients in the older age group had significant lower antidepressant usage proportion than in the younger age group (p < 0.001). Patients with catastrophic illness certificate had lower chance of receiving antidepressants than those without. Patients who received antidepressants had significant higher chance of having neurotic disorders diagnosis (p < 0.001). Gender (p < 0.001), mean age (p < 0.001), insurance status (p < 0.001), and diagnosis (p < 0.001) all showed significant between-group differences.
|Table 1. Demographic data and baseline clinical characteristics of the participants (n = 110,576)|
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[Table 2] shows the results of logistic regression for factors associated with antidepressant use. After adjusted with related factors, old age was found to be associated with equal risk of antidepressant prescriptions (adjusted odds ratios [aORs] = 0.996, 95% confidence interval [CI] = 0.994–0.998, p < 0.001), and female patients also had significant higher risk of antidepressant prescriptions (aOR = 1.36, 95% CI = 1.33–1.40, p < 0.001). Patients with catastrophic illnesses had significant lower risk of antidepressant prescriptions (aOR = 0.86, 95% CI = 0.83–0.89, p < 0.001) than those without catastrophic illnesses. Furthermore, patients with neurotic disorders had significant higher risk of antidepressant prescriptions (aOR = 4.31, 95% CI = 4.14–4.49, p < 0.001) than those with dementia. The model had acceptable coefficient of determination (Nagelkerke pseudo R-squared = 0.27).
|Table 2. Logistic regression for factors associated with antidepressants use|
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In consideration the trend of antidepressant prescription, [Figure 1] shows that the proportion of participants on antidepressants was increased 7.85% over the 10 years study period with statistical significance (from 39.79% to 42.92%, p < 0.001). But different classes of antidepressants showed different trends of prescription. Both of TCAs (from 2.52% to 1.72%, p < 0.001) and SARIs (from 19.40% to 13.32%, p < 0.001) showed significant decrease over the study period. On the contrary, NDRIs (from 0.31% to 1.66%, p < 0.001) showed significant increase over the study period. RIMAs were withdrawn from the study hospital and no more being prescribed since 2009 ([Figure 2]).
|Figure 1. The proportion of participants received and not received antidepressants from 2006 to 2015. *p < 0.05; **p < 0.01; ***p < 0.001 tested using Cochran–Armitage test for trend.|
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|Figure 2. The proportion of participants received antidepressant from 2006 to 2015 (TCA , RIMA , NDRI , SSRI , SNRI , NaSSA , SARI . *p<0.05; **p<0.01; ***p<0.001 tested using Cochran-Armitage test for trend.|
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We also did subgroup analysis to see the effects of age and gender in antidepressant prescriptions. The age group of 75–84 years old showed significant decrease (from 44.55% to 39.96%, p < 0.001) over the study period. On the contrary, the age group of 65–74 (from 37.92% to 44.44%, p < 0.001) and over 85 (from 32.40% to 42.90%, p < 0.001) years old showed significant increase over the study period ([Figure 3]). The female patients showed significant increase (from 40.91% to 45.87%, p < 0.001) over the study period. On the contrary, the male patients (from 38.05% to 37.60%, nonsignificant) showed decreased trend over the study period, but did not reach any significance level ([Figure 4]).
|Figure 3. The proportion of participants received antidepressants in different age groups from 2006 to 2015 65–74***, 74–84***, 85***). *p<0.05; **p<0.01; ***p<0.001 tested using Cochran–Armitage test for trend.|
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|Figure 4. The propor tion of par ticipants received antidepressants in different gender from 2006 to 2015 female***, male). *p<0.05; **p<0.01; ***p<0.001 tested using Cochran–Armitage test for trend.|
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| Discussion|| |
To our best knowledge, this is the first study focusing on the antidepressant prescriptions for elder psychiatric outpatients in psychiatric hospitals in Taiwan. In this study ([Figure 1]), we found that the proportion of antidepressants was increased around 7.85% (from 39.79% in 2006 to 42.92% in 2015). We also found that the proportion of some antidepressants (SSRIs, SNRIs, NDRIs, and NaSSAs) was increased, but some antidepressants (TCAs and SARIs) were decreased over the 10-year study period. The logistic regression ([Table 2]) showed that female gender, younger age, affective disorders, and neurotic disorders were associated with a higher chance of antidepressant prescriptions. We suggest that the results of this study are valuable with important clinical implications in antidepressant prescriptions for the elderly with psychiatric illnesses.
Some of our study results are differences from the studies of other countries ,. Our results ([Figure 2]) showed that the proportion of TCA prescription was decreased over the study period. But several studies demonstrated that the proportion of TCA prescription has been increased. We suggest that the discrepancies are due to different study populations and different disease distributions ,. Many patients at our study hospital had the diagnosis of major psychiatric illnesses such as schizophrenia, bipolar disorder, major depressive disorder, and dementia. Only 4.6% of patients in the study population had the diagnosis of insomnia. Furthermore, the patients with neurotic disorders have the highest TCA prescription rate (2.96%) than the patients with the diagnosis of major psychiatric illnesses (<1%). The elderly patients with those diagnoses may be more vulnerable to the side effects of TCAs than those with minor psychiatric illnesses. A national population-based claims data study  showed that the trend of TCA prescription has been increased during the study period. It may be because TCAs are frequently used for patients with sleep disorders or ill-defined somatic symptoms . The studies of other countries also showed that TCAs are frequently used for patients with nonpsychiatric illnesses such as pain disorder . Besides depressive disorders, antidepressants are approved for the treatment of enuresis, social phobia, generalized anxiety disorder, obsessive compulsive disorder, and bulimia. Off-label use of antidepressants for several clinical conditions is also common . Those factors may lead to the differences of TCA prescription between our study and others.
In our study ([Table 2]), we found that affective psychosis and neurotic disorders had significant higher antidepressant prescriptions than dementia (p < 0.001). The results are understandable and are in line with the data of other studies . On the contrary, schizophrenia, other psychotic disorders, and paranoid states ([Table 2]) had significant lower antidepressant prescriptions than dementia (p < 0.001). Our study showed that the proportion of antidepressant prescriptions for dementia was near 22%. We suggest that the reason may be because depression is a popular comorbid symptom of dementia and antidepressants frequently have been used in behavioral and psychological symptoms of dementia (BPSD) such as agitation, aggressive behaviors, stereotyped behaviors, and hoarding behaviors . A French study also illustrated that up to 34.8% of patients with BPSD have received antidepressants . In real clinical situation, antidepressants are frequently in off-label use for patients with BPSD even lack of research evidence.
Insomnia is also an important factor to influence the prescription of antidepressants for the elderly. Antidepressants have not been officially approved for the treatment of insomnia, but they are frequently being prescribed for patients with insomnia. According to the data of the US, antidepressants are a popular medication to treat insomnia and the proportion reach to 45.1% and the proportion in the elderly is even higher . SARIs such as trazodone and NaSSAs such as mirtazapine have the effects of sedation and drowsy, and both are popular medications for the symptoms of insomnia. Mirtazapine also has better effects in treating depression, anxiety, and obstructive sleep apnea syndrome than trazodone . Our results showed that the diagnosis distribution of patients on NaSSAs was mainly nonpsychotic (i.e., neurotic) disorders, followed by affective psychosis, and then dementia. The diagnosis distribution of patients on SARIs was mainly neurotic disorders, followed by dementia, and then affective psychosis. The prescription of SARIs in the diagnosis of neurotic disorders, dementia, and affective psychosis showed decreasing trend, but the prescription of NaSSAs in the diagnosis of affective psychosis showed increasing trend. It may explain the trend of NaSSAs being increased more than SARIs in this study.
In our study ([Figure 3]), we found that age had significantly negative correlation with antidepressant prescription (p < 0.001). But some studies in other countries show that the proportion of antidepressant prescription has positive correlation with advanced age, and that many antidepressants are SSRIs and SNRIs ,. They suppose that it may be because SSRIs and SNRIs have better profiles for safety and tolerability than those of TCAs, and the prevalence of depressive symptoms is increased with aging . We suggest that those findings may be due to different study populations and the distribution of diagnosis. As mentioned before, many patients have the diagnoses of major psychiatric illnesses in the study hospital and it may be different from other studies. Furthermore, some studies pointed that atypical antipsychotic monotherapy or combination with antidepressants can improve depressive symptoms of mood disorders or psychotic mood disorders ,. Second-generation antipsychotic use for treatment-resistant nonpsychotic depression is also a common clinical practice ,. We suggest that these factors may contribute to the decreased antidepressant prescription with increasing age in our study. Our study also showed that different age groups had different time trends in the prescription rate. The age group of 75–84 years old showed significantly decreased trend, but the age group of 65–74 and over 85 years old showed significantly increased trend over the study period (p < 0.001, [Figure 3]). We do not know the possible reasons of the phenomenon in this study. Further studies are needed to explore this issue.
In the study results, we found that female patients had significantly higher total or individual class of antidepressant prescription than male patients (p < 0.001, [Figure 4]). The results are in line with most of other studies ,,,,. We suggest that the reason may be because the prevalence of depressive disorders and nonpsychotic disorders is higher in female patients. Furthermore, female patients are possibly more willing to accept antidepressant than males ones ,,. But some studies revealed that gender is not an associated factor for antidepressant prescription ,.
Our results showed that the polypharmacy rate of antidepressants was about 18%. Previous studies have demonstrated that the combination of antidepressants, such as SSRIs with mirtazapine, in the treatment of depressive disorders may improve remission rate and decrease relapse rate . But the combinations of antidepressants still need to follow the principles of synergistic effects of different neurotransmitters involving in depressive disorders. Furthermore, we also need to pay attention to the potential side effects of drug–drug interactions. For example, the combination of fluoxetine or paroxetine with trazodone may induce serotonin syndrome .
The readers are warned not to overinterpreting the study results because this study has six limitations.
- We included the data of patients at only one single psychiatric center. The findings from this study may not be generalized to other studies because of differences in local practice patterns.
- The psychiatric diagnoses from the electronic database might be incorrect in some patients and different from those in real clinical circumstances.
- Some variables are related to antidepressant treatment for geriatric studies, but are difficult to retrieve from a retrospective study. Those data include the profiles and severity of psychotic/mood/anxiety symptoms, family support, doctors' and patients' attitude toward a specific medication, previous history and treatment responses of psychotropic medications, the place of residence of the subjects, and the policy changes of the Bureau of National Health Insurance of Taiwan during the study period. To further investigate probable mechanisms explaining the proportion and trend changes over the study period was difficult in this study.
- Patients' laboratory data were not available in this study. Therefore, we did not know the effects of antidepressants on metabolic syndrome and other related profiles which need the data of laboratory examinations.
- We counted the episode of antidepressant prescriptions rather the patient numbers. Thus, a patient may produce more than one episode of antidepressant prescriptions.
- In addition, the treatment guidelines for the elderly with psychiatric illnesses always modify as the time evolution. Therefore, the prescription patterns of psychotropic medications in the elder patients may change in different time periods.
Our results showed that the proportion of elder patients received antidepressants was significantly increased over the study period. Our results also showed that age, gender, and diagnoses were all correlated with the antidepressant prescriptions. But we need to caution the increasing trend of antidepressant prescriptions, especially for patients with off-label use and pay attention to the occurrence of adverse events for this vulnerable population. Elder patients may have some side effects, which is rare in the adult population. For example, SSRIs are associated with falling and hyponatremia in people older than 65 years old with depressive disorders . Other classes of antidepressants are associated with fracture, epilepsy, stroke, and mortality ,. Furthermore, some studies revealed that suicide is associated with antidepressant prescriptions in the elderly ,. Previous studies showed that the adverse events of antidepressants can be appropriately detected and prevented in the elderly . If clinicians can prescribe antidepressants appropriately for psychiatric elder patients, the risk of these adverse events can be minimalized and the quality of care can be maximized.
| Acknowledgments|| |
Both authors contributed equally as the first author of this article. The funding body played no rôle in study design, analysis, or interpretation of the study data in this paper.
| Financial Support and Sponsorship|| |
This study was supported by a grant from the Taoyuan Psychiatric Center, Ministry of Health and Welfare of Taiwan (TYPC-10701).
| Conflicts of Interest|| |
Both authors declare no conflicts of interest in writing this paper.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]