Abstract
Aims
Knowledge on the use of attention‐deficit/hyperactivity disorder (ADHD) medication among older adults is limited. We hypothesized that ADHD medication is used off‐label in adults aged ≥50 years as part of palliative care in e.g. cancer patients. The aim of this study was to describe the use of ADHD medication among adults aged ≥50 years in Denmark.
Methods
Using the Danish health registries, we identified new users ≥50 years of ADHD medication during 2000–2012. We estimated the annual incidence of ADHD medication use and ADHD diagnoses. We described new users of ADHD medication according to co‐medication, comorbidities and assessed the 1‐year cumulative mortality rate. A posthoc analysis allowed us to include new users until 2015.
Results
We identified 6690 new users of ADHD medication from 2000 to 2012. From 2000 to 2015 we observed an increase in the incidence of ADHD medication use from 12.5 to 30.3 per 100 000 person‐years. However, the incidence rate decreased from 2010 to 2015. Throughout the study period, the incidence rate of ADHD diagnoses was low (overall prevalence among new users ≤2%). Opioids were the most frequent comedication used (used by 54%), while cancer was the most frequent diagnosis preceding treatment (prevalence of 52%). The 1‐year cumulative mortality was 50%, primarily driven by patients with a preceding cancer diagnosis.
Conclusion
There was an increase in the incidence of ADHD medication use in adults aged ≥50 years from 2000–2010 and a decreasing incidence from 2010–2015. Our results suggest that ADHD medication is used off‐label in older adults as part of palliative care.
Keywords: aged, attention deficit disorder with hyperactivity, drug utilization, methylphenidate, off‐label use
What is Already Known about this Subject
The use of attention‐deficit/hyperactivity disorder (ADHD) medication in adults has increased; however, knowledge on the use of ADHD medication in older adults is limited.
Based on a previous study, we hypothesized that ADHD medication is used off‐label in adults aged ≥50 years as part of palliative care.
What this Study Adds
Overall, the use of ADHD medication in older adults increased from 2000 to 2015, however, between 2010 and 2015 the use was decreasing.
ADHD medication seems to be used off‐label in adults aged ≥50 years as part of palliative care, especially in patients with cancer.
Researchers should be cautious when relying only on prescription data to identify older adults with ADHD.
Introduction
Over recent decades, the use of medication against attention‐deficit/hyperactivity disorder (ADHD) in adults has increased worldwide 1, 2, 3, 4, 5, 6. In Denmark, use of ADHD medication in adults has raised concern due to the risk profile of these medications, such as the risk of cardiovascular diseases 7. Treatment guidelines and approved medications for adults with ADHD have been missing 7. However, since 2008, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7118, a nonstimulant drug used for ADHD, has been approved for newly diagnosed ADHD in adults 8, 9. Furthermore, since 2011, specific formulations of http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7236 have been approved for the treatment of ADHD in adults aged <65 years 10, 11.
Recently, a Danish study 12 found a surprisingly high mortality among new users of ADHD medication aged >50 years compared to new users aged <50 years. Given that the incidence of ADHD in this population is reported to be low 7, 13, this finding might indicate off‐label use of ADHD medication. Literature suggests that the potential off‐label use of ADHD medication in older patients may be linked to the treatment of symptoms such as opioid induced sedation, fatigue and cognitive dysfunction in terminally ill patients, such as with cancer 14, 15, 16.
Due to the worldwide increase in the use of ADHD medication in the adult population, and the potential for off‐label use, we sought to describe the use of ADHD medication in adults aged ≥50 years in Denmark during the period 2000–2012. We specifically aimed to describe the incidence of ADHD medication use, the incidence of ADHD diagnoses and to describe the clinical characteristics of the population in terms of comorbidities and comedications.
Methods
Using the Danish national health registries, we conducted a drug utilization study identifying new users of ADHD medication aged ≥50 years in Denmark during 2000–2012. We described the use of ADHD medication, the clinical characteristics of this population and the mortality rate.
Data sources
We retrieved data from the Danish National Prescription Registry 17, which contains information on filled prescriptions at outpatient pharmacies from 1995 and onwards for all Danish residents. Thus, we did not have information on in‐patient drug use. We extracted information on somatic and psychiatric diagnoses from the Danish National Patient Register 18 and the Danish Psychiatric Central Research Register 19. The registries contain information on all in‐patient contacts since 1977 and 1969, respectively, and all outpatient and emergency room contacts from 1995. Diagnoses made by general practitioners and private psychiatrists are not covered by these registries. Coding is based on the International Classification of Diseases, 8th revision (ICD‐8) codes until 1994 and ICD‐10 codes thereafter. We identified deaths and migrations from the Danish Civil Registration System 20.
Study population and study drugs
The definition of our study population was based on filling of an ADHD medication. We included all individuals ≥50 years who redeemed their first‐ever prescription since 1995 for methylphenidate (Anatomical Therapeutic Chemical (ATC) code 21: N06BA04) or atomoxetine (ATC: N06BA09) during the study period from 1 January 2000 to 31 December 2012. The date of filling the first prescription marked the index date. Individuals were excluded if they had redeemed a prescription for any ADHD medication (also including http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4804 (ATC: N06BA01) and http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2147 (ATC: N06BA02) prior to the index date and after 1995. As such, all patients had at least a 5‐year run‐in period with no ADHD drug use. Amphetamine and dexamphetamine were only available as magistral preparations during the study period and not completely covered by our registry. Based on publicly available sales data 22, the use of these drugs in patients above 40 years of age was low (medstat.dk). We excluded individuals who used http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7555 (ATC: N06BA07) prior to index date because the main indication for modafinil is narcolepsy and patients initiating modafinil before methylphenidate or atomoxetine most likely have narcolepsy. These patients were excluded as we were only interested in patients using ADHD medications for ADHD or other off‐label indications. Furthermore, to ensure full coverage of our study population we excluded individuals with a migration history any time before and up to 1 year after index date. For individuals included later than July 2012, we did not have data on migration for 1 full year after index date.
Data analysis
Incidence rates of ADHD medication use
We calculated the annual incidence rates [per 100 000 person‐years (py)] of ADHD medication use from 2000–2012, stratified into age categories (50–64 years, 65–79 years and 80+ years). We used the number of new users in the relevant age strata as the numerator and the entire Danish population aged ≥50 years by 1 January in the relevant age strata as the denominator 22 as the number of prevalent users is negligible. A posthoc analysis allowed us to assess the incidence of ADHD medication use from 2013–2015, but with no data available on migration from July 2013 and onwards.
Incidence rates of ADHD diagnoses
To calculate the annual incidence rates (per 100 000 py) of ADHD diagnoses from 2000–2012, stratified into age categories (50–64 years, 65–79 years and 80+ years), we identified all Danes aged ≥50 years with at least one record of an ADHD diagnosis in our registries. We excluded those that did not receive their first diagnosis within the study period. As such, all patients had a run‐in period of at least 5 years. We used the number of Danes with a new ADHD diagnosis in the relevant age strata as the numerator and the entire Danish population aged ≥50 years by 1 January in the relevant age strata as the denominator 22 as the number of patients with an ADHD diagnosis is negligible.
Characteristics of the study population
We described our study population of new ADHD medication users according to a number of characteristics, including age at index date, sex, index medication, use of selected comedications and comorbidities (see Appendix 1) prior to index date. Characteristics of the study population were stratified into age categories as specified above. Use of selected comedications was defined as having filled at least one prescription within 6 months prior to index date. Comorbidities were assessed within 1 year prior to index date, and any time prior to index date as a sensitivity analysis. The presence of an ADHD diagnosis was assessed any time prior to index date (see Appendix 1).
Mortality
For each age category, we calculated the 1‐year cumulative mortality rate, specified by calendar year of the index prescription. Estimates were standardized by age and sex, using the study population in 2012 as the reference population. Further, we performed a Kaplan–Meier survival analysis to depict the cumulative mortality occurring during the first year after index date. As we did not have data on death in 2013, these analyses were restricted to new users starting medication in the period 2000–2011.
Supplementary analyses
We performed several supplementary analyses. First, we stratified the incidence of ADHD medication use by the five regions of Denmark (i.e. Capital Region of Denmark, Region Zealand, Region of Southern Denmark, Central Denmark Region, and North Denmark Region). We did this to assess whether there were any regional differences in ADHD medication use during the period 2008–2012. Second, to assess differences by sex, we stratified our main analysis by this parameter. Lastly, to test our hypothesis of use of ADHD medication in palliative care, we stratified our main analysis by the presence of cancer 1 year before index date, as well as death within 1 year after index date (for those starting medication in the period 2000–2011).
Statistical analysis
To test for trends over time, we performed a linear regression analysis of the incidence rate as a function of index year. Likewise, we performed a linear regression analysis of the mortality rate as a function of index year. We used the slope and the corresponding confidence intervals to interpret on the trends over time. If the confidence interval of the slope did not contain zero, we interpreted this as a statistically significant trend (positive or negative) over time. We reported the P‐values for the t‐test of coefficients in the linear regression model. We reported confidence intervals for incidence rates of ADHD medication use and ADHD diagnoses. The significance level was set to 0.05. Data analysis was performed using STATA Release 14.2 (StataCorp, College Station, Texas, USA).
Ethical approval
The study was approved by the Danish Data Protection Agency and Statistics Denmark's Scientific Board. Ethical approval was not needed for this study according to Danish legislation 23.
Nomenclature of targets and ligands
Key protein targets and ligands in this article are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY 24, and are permanently archived in the Concise Guide to PHARMACOLOGY 2017/18.
Results
A total of 6705 new users of ADHD medication aged ≥50 years were identified between 2000 and 2012. After excluding 15 individuals due to migration, the final study was based on data from 6690 individuals.
From 2000 to 2012, we observed a significant increase in the overall incidence rate of new ADHD medication use (P < 0.001); from 2000 to 2010, we observed an increase from 12.5 to 49.3 per 100 000 py, and from 2010 to 2012 we observed a decrease from 49.3 to 38.0 per 100 000 py (see age stratified incidence rates in Figure 1 and Supporting Table S1). We observed similar trends between the different age groups; however, we observed the largest increase among 50–64‐year‐olds (Figure 1). The posthoc analysis showed a slight decrease in the incidence rate, reaching 30.3 per 100 000 py in 2015 (Supporting Figure 1 and Supporting Table S1).
Figure 1.
Incidence rates (per 100 000 person‐years) of new users of attention‐deficit/hyperactivity disorder medication (left graph) and incidence rates of attention‐deficit/hyperactivity disorder diagnoses (right graph) per calendar year (2000–2012). Stratified by age
We observed regional variations in the incidence of ADHD medication use, most pronounced among the 50–79‐year‐olds; the incidence was highest in Region Zealand (2012: around 54 per 100 000 py) and in the Capital Region of Denmark (2012: around 61 per 100 000 py), and lowest in the region of Southern Denmark (2012: 20 per 100 000 py; Supporting Figure S2).
The incidence rate of new ADHD diagnoses was low throughout the study period, and increased only among users aged 50–64 years (0.1 to 7.3 per 100 000 py, P < 0.001; Figure 1 and Table S1).
The characteristics of the study population are shown in Table 1. The median age was 62 years (interquartile range, 55–71 years), and 52% were male. The majority used methylphenidate (98%) with immediate release (91%) being the most common formulation. Use of other psychotropic drugs was common; opioids (used by 54%), antidepressants (45%) and hypnotic and sedatives (34%) were the most frequently used comedications prior to index date (Table 1). Stratification revealed variations between the different age categories (Table 1). Among individuals ≥65 years, use of opioids, loop‐diuretics and antithrombotic agents was more common compared to individuals below 65 years (Table 1). Cancer was the most common diagnosis among new users of ADHD medication (52%, Table 1). We found the highest prevalence of cancer in individuals ≥65 years (up to 70%; Table 1), and in individuals dying within 1 year after index date (93%; Supporting Table S2). Use of other psychotropic drugs, especially opioids (84%), was more common in patients with cancer compared to patients without cancer (Supporting Table S2). The prevalence of other comorbidities, including psychiatric disorders, was generally low (≤8%; Table 1). The same patterns were observed when assessing comorbidity any time prior to index date. The prevalence of ADHD diagnoses in the study population was low (2%) and an ADHD diagnosis was only observed among individuals younger than 65 years (4%; Table 1).
Table 1.
Characteristics of new users of attention‐deficit/hyperactivity disorder medication aged ≥50 years, 1 January 2000 to 31 December 2012
| All (n = 6690) | Age 50–64 years (n = 3781) | Age 65–79 years) (n = 2305) | Age 80+ years (n = 604) | |
|---|---|---|---|---|
| Median age at index date, years (IQR) a | 62 (55–71) | 56 (52–60) | 71 (67–75) | 83 (81–86) |
| Sex, n (%) | ||||
| Male | 3451 (52) | 1919 (51) | 1234 (54) | 298 (49) |
| Female | 3239 (48) | 1862 (49) | 1071 (46) | 306 (51) |
| Index medication, n (%) | ||||
| Methylphenidate | 6571 (98) | 3674 (97) | 2295 (100) | 602 (100) |
| Atomoxetine | 119 (2) | 107 (3) | 10 (0) | n < 5 |
| ADHD diagnosis any time before index date, n (%) | 156 (2) | 151 (4) | n < 5 | n < 5 |
| Comedication 6 months before index date, n (%) | ||||
| Opioids | 3588 (54) | 1661 (44) | 1556 (68) | 371 (61) |
| Antiepileptics | 1249 (19) | 760 (20) | 417 (18) | 72 (12) |
| Antipsychotics | 1016 (15) | 626 (17) | 324 (14) | 66 (11) |
| Anxiolytics | 1917 (29) | 1037 (27) | 723 (31) | 157 (26) |
| Hypnotics and sedatives | 2251 (34) | 1112 (29) | 916 (40) | 223 (37) |
| Antidepressants | 3018 (45) | 1776 (47) | 994 (43) | 248 (41) |
| Drugs used in addictive disorders | 613 (9) | 404 (11) | 183 (8) | 26 (4) |
| High‐ceiling diuretics (loop‐diuretics) | 1014 (15) | 355 (9) | 486 (21) | 173 (29) |
| Beta‐blocking agents | 763 (11) | 330 (9) | 344 (15) | 89 (15) |
| Lipid‐modifying agents, plain | 933 (14) | 442 (12) | 403 (17) | 88 (15) |
| Antithrombotic agents | 1539 (23) | 535 (14) | 729 (32) | 275 (46) |
| Comorbidities 1 year before index date, n (%) | ||||
| Hypertensive heart disease | 14 (0) | n < 5 | 7 (0) | n < 5 |
| Hypertensive renal disease | n < 5 | n < 5 | n < 5 | n < 5 |
| Angina pectoris | 111 (2) | 46 (1) | 52 (2) | 13 (2) |
| Acute myocardial infarction | 38 (1) | 13 (0) | 15 (1) | 10 (2) |
| Atrial fibrillation and flutter | 200 (3) | 50 (1) | 105 (5) | 45 (7) |
| Heart failure | 101 (2) | 22 (1) | 53 (2) | 26 (4) |
| Intracerebral haemorrhage | 33 (0) | 14 (0) | 19 (1) | n < 5 |
| Cerebral infarction | 68 (1) | 21 (1) | 30 (1) | 17 (3) |
| Atherosclerosis | 52 (1) | 14 (0) | 25 (1) | 13 (2) |
| Type 2 diabetes mellitus | 532 (8) | 226 (6) | 247 (11) | 59 (10) |
| Other chronic obstructive pulmonary disease | 247 (4) | 75 (2) | 137 (6) | 35 (6) |
| Parkinson's disease | 33 (0) | n < 5 | 20 (1) | 9 (1) |
| Any malignant neoplasms (cancer) b | 3446 (52) | 1431 (38) | 1621 (70) | 394 (65) |
| Malignant neoplasm of colon | 424 (6) | 164 (4) | 195 (8) | 65 (11) |
| Malignant neoplasm of bronchus and lung | 710 (11) | 291 (8) | 356 (15) | 63 (10) |
| Malignant neoplasm of breast | 438 (7) | 212 (6) | 182 (8) | 44 (7) |
| Malignant neoplasm of prostate | 453 (7) | 109 (3) | 268 (12) | 76 (13) |
| Malignant neoplasms of brain | 63 (1) | 37 (1) | 20 (1) | n < 5 |
| Any psychiatric diagnoses c | 337 (5) | 257 (7) | 60 (3) | 20 (3) |
IQR; interquartile range (Q25–Q75)
Except nonmelanoma skin cancer
F00–F98 except F90 and F98.8
We observed variations in the 1‐year mortality rate over time between the different age groups (Supporting Figure S3). Throughout the study period, the 1‐year mortality rate declined for those aged 50–64 years (from around 53% to 23%, P < 0.001; Supporting Figure S3). For individuals aged ≥65 years, the mortality rate was slightly increasing (Supporting Figure S3). The overall standardized 1‐year mortality rate during the study period was 50%. Figure 2 shows the survival analysis stratified by age. Stratification revealed that around 88% of individuals with cancer died within 1 year after index date compared to around 7% of individuals without cancer (Supporting Figure S4).
Figure 2.
Kaplan–Meier plot of survival probability of new users of attention‐deficit/hyperactivity disorder medication initiating treatment between 2000 and 2011. Stratified by age
We performed a posthoc analysis investigating the top ten most frequent diagnoses in the study population 1 year and any time prior to index date. We did this to capture relevant diagnoses not specified beforehand as potential off‐label use. Pain was the most frequently registered diagnosis in this analysis (1‐year analysis: 29%; Supporting Table S3). Other identified diagnoses included malaise and fatigue, nausea and vomiting, other functional intestinal disorders, sleep disorders, and essential hypertension.
Throughout all analyses, we observed no differences when stratifying by sex (data not shown).
Discussion
We document a marked increase in ADHD medication use in adults aged ≥50 years during the period 2000–2010 and a decrease from 2010 and onwards while observing a low incidence of ADHD diagnoses. Among old new users of ADHD medication, a cancer diagnosis was common and the 1‐year mortality was high. Together, this indicates off‐label use of ADHD medication (e.g. as part of palliative care in cancer patients).
The incidence of ADHD medication use increased from 2000–2010, with some regional variations from 2008–2012. The increase in the use of ADHD medication in older adults is supported by observations from other countries between 1994 and 2012 1, 2, 3. In 2010, a Danish report underlined the increased use of methylphenidate in adults and raised concern about the risk profile 7. This may have contributed to the decline in the use of ADHD medication observed between 2010 and 2015 7.
Our results generally support our hypothesis that ADHD medication is used off‐label in older adults as part of palliative care. First, the incidence and prevalence of ADHD diagnoses was low, and cancer was by far the most prevalent diagnosis preceding treatment initiation. Second, our posthoc analysis revealed common diagnoses preceding treatment initiation that could potentially be related to cancer or the treatment of cancer (e.g. pain, fatigue, nausea and vomiting). Third, 93% of new users of ADHD medication who died within 1 year after treatment initiation had a diagnosis of cancer. Use of methylphenidate in cancer patients as part of palliative care has been described in two previous studies 25, 26. During the terminal stage of cancer, methylphenidate has been found to alleviate the following symptoms: opioid induced sedation 15, 27, 28, 29; fatigue 15, 16, 30, 31; depression 28, 32, 33; loss of appetite 32, 34; and cognitive dysfunction 15, 30.
A hospital diagnosis of cancer was registered in 93% of people dying within 1 year after initiating treatment. Among the remaining 7% of individuals dying within the 1st year, we found more frequent use of loop‐diuretics and antithrombotic agents as a possible indicator of frailty 35, 36.
While the 1‐year mortality rate increased slightly for individuals aged ≥65 years during the study period, it decreased for individuals aged 50–64 years. This decrease in mortality rate might be explained by a dilution effect due to increased on‐label use of ADHD medication within this age stratum. This is supported by the observed increase in the incidence of ADHD diagnoses among 50–64‐year‐olds for whom some formulations of ADHD medication have been approved 9, 10.
Data on the use of ADHD medication from dispensing data are often subject to uncertainty about clinical indications. Our study shows that researchers should be cautious when relying only on dispensing data to define patients with ADHD above the age of 50 years. Furthermore, researchers analyzing use of ADHD medication in adults should be aware of use that may not represent on‐label use in their interpretation of results.
Our study has several strengths. First, we used data from the Danish nationwide health registries, described to have complete registration and high validity 17, 18, 19, 20. Further, data from the Danish National Prescription Registry were available since 1995, ensuring correct classification of new users of ADHD medication.
Our study also has some limitations. First, the indication for treatment with ADHD medication was not available from the Danish National Prescription Registry. ADHD medication might be used in the treatment of narcolepsy in an adult population, however, the prevalence of this disorder is generally low (0.05%) 37. Our posthoc analysis showed a prevalence of 8% for sleep disorders including narcolepsy. Although narcolepsy only accounts for a fraction of this, we cannot rule out that a few people of our study population were treated with ADHD medication due to a diagnosis of narcolepsy. Second, the prevalence of ADHD diagnoses could only be based on hospital discharge diagnosis data. As adult patients might receive ADHD diagnoses outside the hospital setting (e.g. from general practitioners or psychiatrists), we might underestimate the true prevalence of ADHD in this population.
In conclusion, our study revealed an increase in the incident use of ADHD medication in adults aged ≥50 years during 2000–2010, however decreasing from 2010 and onwards. While we cannot rule out the possibility of a small fraction of on‐label use in our population, due to ADHD in individuals aged <65 years or narcolepsy for examples, ADHD medication seems to be primarily used off‐label as part of palliative care, especially in patients with cancer.
Competing Interests
There are no competing interests to declare.
Contributors
All authors contributed to the design of the study. L.R. and A.P. performed the data analysis. All authors contributed to the interpretation of data. S.S.O. and L.R. drafted the first version of the paper, and all authors were involved in critically revising the text. All authors read and approved the final version of the paper.
Supporting information
Figure S1 Incidence rates (per 100 000 person‐years) of new users of attention‐deficit/hyperactivity disorder medication per calendar year (2000–2015). Stratified by age
Figure S2 Incidence rates (per 100 000 person‐years) of new users of attention‐deficit/hyperactivity disorder medication during 2008–2012 across the five Danish Regions. (A) 50–64 years, (B) 65–79 years and (C) shows 80+ years
Figure S3 One‐year mortality rate (%) of new users of attention‐deficit/hyperactivity disorder medication between 2000 and 2011 stratified by age, standardized to the population in 2012
Figure S4 Kaplan–Meier plot of survival probability of new users of attention‐deficit/hyperactivity disorder medication between 2000 and 2011. Stratified by a diagnosis of cancer
Table S1 Incidence rates (per 100 000 person‐years) of new users of attention‐deficit/hyperactivity disorder medication and attention‐deficit/hyperactivity disorder diagnoses per calendar year (2000–2015). Overall and stratified by age
Table S2 Characteristics of new users of attention‐deficit/hyperactivity disorder medication ≥50 years, 1 January 2000 to 31 December 2012. Stratified by the presence of cancer and death within 1 year after index date
Table S3 Posthoc analysis; the 10 most frequent diagnoses in the study population 1 year prior to index date
Appendix 1.
| Use of drugs (6 months prior to index date) | ||
|---|---|---|
| Opioids | ATC code | N02A |
| Antiepileptics | ATC code | N03A |
| Antipsychotics | ATC code | N05A |
| Anxiolytics | ATC code | N05B |
| Hypnotics and sedatives | ATC code | N05C |
| Antidepressants | ATC code | N06A |
| Drugs used in addictive disorders | ATC code | N07B |
| High‐ceiling diuretics (loop‐diuretics) | ATC code | C03C |
| Beta‐blocking agents | ATC code | C07A |
| Lipid‐modifying agents, plain | ATC code | C10A |
| Antithrombotic agents | ATC code | B01A |
| Diagnoses (12 months prior to index date) | ||
|---|---|---|
| Hypertensive heart disease | ICD‐10 | I11 |
| Hypertensive renal disease | ICD‐10 | I12 |
| Angina pectoris | ICD‐10 | I20 |
| Acute myocardial infarction | ICD‐10 | I21 |
| Atrial fibrillation and flutter | ICD‐10 | I48 |
| Heart failure | ICD‐10 | I50 |
| Intracerebral haemorrhage | ICD‐10 | I61 |
| Cerebral infarction | ICD‐10 | I63 |
| Atherosclerosis | ICD‐10 | I70 |
| Type 2 diabetes mellitus a | ICD‐10 | E11 |
| Other chronic obstructive pulmonary disease | ICD‐10 | J44 |
| Parkinson's disease | ICD‐10 | G20 |
| Any malignant neoplasms (cancer), except nonmelanoma skin cancer | ICD‐10 | C00‐C97, except C44 |
| Malignant neoplasms of colon | ICD‐10 | C18 |
| Malignant neoplasms of bronchus and lung | ICD‐10 | C34 |
| Malignant neoplasms of breast | ICD‐10 | C50 |
| Malignant neoplasms of prostate | ICD‐10 | C61 |
| Malignant neoplasms of brain | ICD‐10 | C71 |
| Organic, including symptomatic, mental disorders | ICD‐10 | F00‐F09 |
| Dementia in Alzheimer's disease | ICD‐10 | F00 |
| Vascular dementia | ICD‐10 | F01 |
| Mental and behavioral disorders due to psychoactive substance abuse | ICD‐10 | F10‐F19 |
| Schizophrenia and related disorders | ICD‐10 | F20‐F29 |
| Mood disorders | ICD‐10 | F30‐F39 |
| Neurotic, stress‐relates, and somatoform disorders | ICD‐10 | F40‐F48 |
| Behavioral syndromes associated with psychological disturbances and physical factors | ICD‐10 | F50‐F59 |
| Eating disorders | ICD‐10 | F50 |
| Disorders of adult personality and behavior | ICD‐10 | F60‐F69 |
| Specific personality disorders | ICD‐10 | F60 |
| Mental retardation | ICD‐10 | F70‐F79 |
| Disorders of psychological development | ICD‐10 | F80‐F89 |
| Behavioral and emotional disorders with unset occurring in childhood and adolescence | ICD‐10 | F90‐F98, except F90, F98.8 |
| Diagnosis (any time prior to index time) | ||
|---|---|---|
| Attention‐deficit/hyperactivity disorder | ICD‐8 | 308.01 |
| Attention‐deficit/hyperactivity disorder | ICD‐10 | F90, F98.8 |
Diabetes mellitus is defined as having filled at least one prescription within 1 year prior to index date or having a diagnosis 1 year prior to index date
ICD, International Classification of Disease; ATC, Anatomical Therapeutic Chemical
Ormhøj, S. S. , Pottegård, A. , Gasse, C. , and Rasmussen, L. (2018) Use of attention‐deficit/hyperactivity disorder medication among older adults in Denmark. Br J Clin Pharmacol, 84: 1505–1513. doi: 10.1111/bcp.13569.
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Associated Data
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Supplementary Materials
Figure S1 Incidence rates (per 100 000 person‐years) of new users of attention‐deficit/hyperactivity disorder medication per calendar year (2000–2015). Stratified by age
Figure S2 Incidence rates (per 100 000 person‐years) of new users of attention‐deficit/hyperactivity disorder medication during 2008–2012 across the five Danish Regions. (A) 50–64 years, (B) 65–79 years and (C) shows 80+ years
Figure S3 One‐year mortality rate (%) of new users of attention‐deficit/hyperactivity disorder medication between 2000 and 2011 stratified by age, standardized to the population in 2012
Figure S4 Kaplan–Meier plot of survival probability of new users of attention‐deficit/hyperactivity disorder medication between 2000 and 2011. Stratified by a diagnosis of cancer
Table S1 Incidence rates (per 100 000 person‐years) of new users of attention‐deficit/hyperactivity disorder medication and attention‐deficit/hyperactivity disorder diagnoses per calendar year (2000–2015). Overall and stratified by age
Table S2 Characteristics of new users of attention‐deficit/hyperactivity disorder medication ≥50 years, 1 January 2000 to 31 December 2012. Stratified by the presence of cancer and death within 1 year after index date
Table S3 Posthoc analysis; the 10 most frequent diagnoses in the study population 1 year prior to index date