2023 Volume 46 Issue 9 Pages 1211-1216
Attention deficit/hyperactivity disorder (ADHD) is a common developmental disorder. This study aims to clarify the timing of diagnosis of ADHD in working-age workers with psychiatric comorbidities using large claims data in Japan. Based on a literature survey, we identified 10 typical comorbidities of ADHD. Among 3064162 participants with social insurance, 215060 working-age workers who were diagnosed with the 10 typical comorbidities of ADHD were included. Cohort 1 consisted of 96994 patients with the index date set as the earliest date of diagnosis of a comorbidity within the 12-month screening and 12-month observation periods. In cohort 2, 107436 patients were included, and the first date of diagnosis of each comorbidity was used as the index month. In cohort 1, 0.19% of the patients were diagnosed with ADHD after being diagnosed with a typical comorbidity. In cohort 2, 4 out of 4 patients with ADHD and obsessive-compulsive disorders were diagnosis ADHD after obsessive-compulsive disorders. Pervasive developmental disorders were the highest comorbidity of ADHD for 62 out of 566 (11.0%) patients. This is the first study to determine the proportion of ADHD with typical comorbidities in working-age workers in Japan. Our findings highlight the need for timely diagnosis of ADHD to improve patients’ QOL.
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common developmental disorders of childhood.1) Generally, diathesis has been associated with the onset of ADHD from childhood; ADHD is not frequently diagnosed as it does not present with severe symptoms that impact social life.2) In the general population, the prevalence of ADHD in children is 5.9–7.1%, and 1.65–5.0% in adults.2–7) Previously, mostly pediatric ADHD patients are not focused because ADHD improve according to aging from the guidelines.8,9) Recently, there has been an increasing awareness of ADHD in society, which has led to a growing number of workers taking note of issues such as frequent instances of carelessness and diminished concentration. This phenomenon has garnered significant attention.8–10) However, ADHD has a wide and heterogeneous clinical presentation. Adults who have not been diagnosed with ADHD report feeling uneasy at work or in social situations,11) and often assume that the discomfort is due to other reasons including lack of expertise or carelessness. As a result, these individuals miss out on being diagnosed with ADHD and receiving adequate treatment.12–14) Therefore, failure in adequate diagnosis of ADHD in patients with mild disease is a global concern as it impacts the QOL and leads to socio-economic burdens.12–14)
Over 80% of patients with ADHD have psychiatric comorbidities including substance abuse and dependence, mood disorders, and anxiety or personality disorders.15–17) Mental and behavioral disorders due to psychoactive substance use are one of the most prominent comorbidities, particularly in adult patients with ADHD.15) Nonetheless, these comorbidities present after the onset of ADHD; therefore, the timing of diagnosis of ADHD and its common comorbidities need to be determined. Even though active treatment is not required for all patients with ADHD, knowing whether or not they have ADHD is important for themselves and their families.
Approximately 85.8% of patients with ADHD reportedly did not reach the threshold for diagnosis of ADHD in childhood.18) Although medication for ADHD therapy was provided to only 25.2% of patients with ADHD, 80% of these patients had beneficial outcomes following therapy.19) The prevalence of ADHD among workers in the United States was estimated to be 4.2%, and was associated with 35.0 d lost at work, and a total loss of $19.5 billion each year.18) Early timing of diagnosis of ADHD is important to relieve the undesirable symptoms in affected individuals. For example, depression is as one of the major comorbidities of patients with ADHD.9) Daviss et al. reported that a delay in ADHD diagnosis was the predictor that preceded the onset of any first depression related episode.20) Further, these authors concluded that ADHD pharmacotherapy reduces the risk of later major depressive disorders.20)
As aforementioned, understanding the timing of diagnosis of comorbidities for patients with mild ADHD is critical to assess its impact from an epidemiological perspective. However, there is a paucity of information, especially on working-age workers with ADHD, and the timing of ADHD diagnosis. Therefore, in this study, we used large claims data to assess ADHD and the 10 most common comorbidities associated with ADHD in working-age workers in Japan.
In 2017, the Japan Medical Data Center (JMDC, Tokyo, Japan) claim database consisted of anonymized data of approximately 4.2 million people (inpatient, outpatient, and pharmacy claims) aged ≤74 years from over 90% of the hospitals in Japan. The database includes working individuals who have social insurance and their families. As of 2017, the database represented 3% of the total population of Japan.21,22)
Case Identification and DefinitionWe used the dataset from 3064012 participants included in the JMDC database from January 2005 to June 2017. Out of these, we excluded family members of workers with social insurance (n = 1468789). From the remaining individuals, we identified patients with the typical 10 comorbidities of ADHD such as mental and behavioral disorders due to psychoactive substance use (ICD 10 code for F10–19), bipolar affective disorder (ICD 10 code for F31), depressive episode (ICD 10 code for F32), phobic anxiety disorders/other anxiety (ICD 10 code for F40/F41), obsessive-compulsive disorders (ICD 10 code for F42), eating disorders/symptoms and signs concerning food and fluid intake (ICD 10 code for F50/R63), specific developmental disorders of speech and language/specific developmental disorders of scholastic skills (ICD 10 code for F80/F81), pervasive developmental disorders (ICD 10 code for F84), conduct disorders (ICD 10 code for F91), and tic disorder (ICD 10 code for F95) (n = 215060).23) The definition of ADHD was based on the ICD 10 code for F90 and medication therapy of atomoxetine (ATC code for N06BA09) or methylphenidate (ATC code for N06BA04). We permitted to include differences in timing between ADHD diagnosis and medication therapy in this study because medication therapy can be initiated after primary treatment of psychosocial therapy including adjusting the environment.8) The timing of ADHD diagnosis was used to time the added ICD 10 code of ADHD for each patient.
Study DesignWe identified patients with 12-month screening and 12-month observation periods from the index month [0] (Fig. 1, Supplementary 1, 2). In cohort 1, the index month [0] meant the first diagnosis time of any of the 10 typical psychiatric disorders. The patient information from this cohort was used uniquely. In this cohort, we assessed the timing of newly diagnosed ADHD at five different times from the index month [month 0]. The timings were as follows: (1) looking at newly diagnosed ADHD from the time the patient was entered into the JMDC [from the time of patient entry into the JMDC cohort to −13 months from the index month], (2) looking at newly diagnosed ADHD until 12 months [−1 month until −12 months from the index month], (3) simultaneous diagnosis of the 10 typical psychiatric disorders and ADHD [index month: month 0], (4) observing newly diagnosed ADHD until +11 months [+1 month toward +11 months from the index month], and (5) observing newly diagnosed ADHD until the time a patient leaves the JMDC cohort [+12 months from the index month until the time a patient leaves the JMDC cohort] (Supplementary 1).
ADHD, Attention-Deficit/Hyperactivity Disorder.
In cohort 2, the index month [0] meant the first diagnosis time of each of the 10 typical psychiatric disorders. The patient information in this cohort was permitted to use repeatedly, if patients have one or more 10 typical psychiatric disorders. In this cohort, we assessed the timing of newly diagnosed ADHD from three different times from the index month [month 0]. The timings were as follows: (1) the “before” group entailed looking at new ADHD diagnoses until month 12 [−1 month until −12 months from the index month], (2) the “simultaneously” group included patients diagnosed with one of the 10 typical psychiatric disorders and ADHD [month 0], (3) the “after” group entailed observing new diagnoses of ADHD until month 11 [+1 month until +11 months from the index month] (Supplementary 2).
Calculation for the Proportion in Cohorts 1 and 2Patient characteristics are represented as median and range or mean ± standard deviation. In cohort 1, we used the below calculation to assess groups (1) to (5) as defined above. Briefly, patients were uniquely assigned to groups (1) to (5) or to the without ADHD patient group. In patients assigned to (2), (3), and (4) a “proportion” was calculated as a primary endpoint. The denominator and numerator were calculated using 96994 as the total cohort 1 patients as shown below:
1. Proportion of (2)—looking back at newly diagnosed ADHD until month 12
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2. Proportion of (3)—ADHD simultaneously diagnosed with any of the 10 typical psychiatric diseases:
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3. Proportion of (4)—observing newly diagnosed ADHD until +11 months
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On the other hand, we present “the number of patients” in patients assigned to the above defined groups of (1) and (5) because patients diagnosed with or without ADHD had different observation/follow-up periods.
In cohort 2, the numerator is the number of cases diagnosed with ADHD and the denominator is the patients without an ADHD diagnosis at “before,” “simultaneously” and “after” diagnosis of any of the 10 typical comorbidities. The calculation of proportions in cohort 2 followed the same method as in cohort 1. Briefly, if there are patients with bipolar affective disorder who received a diagnosis of ADHD prior to the bipolar diagnosis, the number of such patients is subtracted from the denominator when calculating the timing of “simultaneously” or “after” in the group of bipolar affective disorder. Data analysis was performed using JMP 16® (SAS Institute Inc., Cary, NC, U.S.A.).
Study Endpoints and Statistical AnalysisThe primary endpoint was the proportion of the calculations of cohort 1 mentioned above, viz. (2)—looking back at newly diagnosed ADHD until month 12 [−1 month until −12 months from the index month], (3) simultaneous diagnosis of ADHD with any of the 10 typical psychiatric diseases [index month: month 0], and (4) observing newly diagnosed ADHD until +11 months [+1 month toward +11 months from the index month]. The secondary endpoint was the proportion of calculations of cohort 2 mentioned above for the three different timings, viz. (1) before, (2) simultaneously, or (3) after being diagnosed with any of the typical 10 comorbidities.
Ethics DeclarationThe commercially available JMDC database used in this study is an anonymized processed information database based on Japan’s Personal Information Protection Law, thus individual informed consent was not required. In addition, ethical approval was waived for this study because according to the Ethical Guidelines for Clinical Research in Japan, research using anonymized processed information does not require ethical approval. SHOWA University Clinical Research Review Board waived the need to review the study.
A total of 96994 patients (male/female: 76745/20249, 40 ± 11 years old) comprised cohort 1 in this study. In cohort 2, a total of 107436 patients (male/female: 84931/22505, 40 ± 11 years old) were identified. Among these patients, the most frequent diagnosis was a depressive episode (ICD 10 code for F32) (n = 44168), followed by phobic anxiety disorders/other anxiety (ICD 10 code for F40/F41) (n = 33032), and eating disorders/symptoms and signs concerning food and fluid intake (ICD 10 code for F50/R63) (n = 26585) (Table 1).
| Cohort 1 (n = 96994) | Cohort 2 (n = 107436) | |
|---|---|---|
| Age, years, mean (S.D.) | 40 (11) | 40 (11) |
| Sex, n (%) | ||
| Male | 76745 (79.1) | 84931 (79.1) |
| Female | 20249 (20.9) | 22505 (20.9) |
| Diseases, n (%) | ||
| Depressive episode (F32) | 35741 (36.8) | 44168 (34.2) |
| Phobic anxiety disorders (F40), Other anxiety (F41) | 22464 (23.2) | 33032 (25.6) |
| Eating Disorders (F50), Symptoms and signs concerning food and fluid intake (R63) | 21314 (22.0) | 26585 (20.6) |
| Mental and behavioral disorders due to psychoactive substance use (F10–19) | 15232 (15.7) | 17962 (13.9) |
| Bipolar affective disorder (F31) | 1544 (1.6) | 5481 (4.3) |
| Obsessive compulsive disorders (F42) | 248 (0.3) | 861 (0.7) |
| Pervasive developmental disorders (F84) | 276 (0.3) | 566 (0.4) |
| Specific developmental disorders of speech and language (F80), Specific developmental disorders of scholastic skills (F81) | 134 (0.1) | 207 (0.2) |
| Tic disorders (F95) | 40 (0.04) | 61 (0.05) |
| Conduct disorders (F91) | 1 (0) | 1 (0) |
In our study population, 595/96994 patients were diagnosed with ADHD. The proportion for ADHD diagnosis timing for “(2) looking back at newly diagnosed ADHD until month 12” was 0.04% (n = 43/96981). Those for “(3) simultaneous diagnosis of ADHD with any of the 10 typical psychiatric diseases” and “(4) observing newly diagnosed ADHD until +11 months” were 0.14% (n = 131/96938) and 0.19% (n = 186/96807), respectively (cohort 1). Other outcomes for the number of patients in “(1) looking at newly diagnosed ADHD from the time the patient was entered into the JMDC” and “(5) observing newly diagnosed ADHD until the time a patient leaves the JMDC cohort” were observed in 13 and 222 study patients (cohort 1).
Secondary Endpoint: Proportion of Patients with ADHD Diagnosis “before,” “simultaneously,” or “after” Diagnosis of Any of the 10 Typical Comorbidities in Working-Age Workers (Cohort 2)In cohort 2, the commonest comorbidities of ADHD were pervasive developmental disorders (Fig. 2), with a proportion of 1.06% (6/566) in patients with ADHD diagnosed before the diagnosis of a typical comorbid condition, followed by specific developmental disorders of speech and language/specific developmental disorders of scholastic skills and bipolar affective disorder at 0.48% (1/207) and 0.24% (13/5481), respectively. Simultaneous diagnosis of ADHD and typical comorbidities were highest in pervasive developmental disorders for 6.07% (34/560), bipolar affective disorder for 0.33% (18/5468), and depressive episode for 0.20% (89/44127) of the patients. On the other hand, ADHD diagnosis after the diagnosis of typical comorbidities was highest in pervasive developmental disorders for 4.18% (22/526), specific developmental disorders of speech and language/specific developmental disorders of scholastic skills for 0.97% (2/206), and bipolar affective disorder for 0.70% (38/5450) of patients.
The timing for patients diagnosed with ADHD and the typical 10 comorbidities in cohort 2 were assessed (Table 2). For patients with ADHD diagnosed “after,” the most frequent comorbidities were obsessive-compulsive disorders for 100% (4/4), eating disorders/symptoms and signs concerning food and fluid intake for 75.0% (21/28), specific developmental disorders of speech and language/specific developmental disorders of scholastic skills for 66.7% (2/3), mental and behavioral disorders due to psychoactive substance use for 57.1% (4/7), bipolar affective disorder for 55.1% (38/69), depressive episode for 54.1% (153/283), and phobic anxiety disorders/other anxiety for 52.3% (56/107) of patients.
| Cases (n) | Number of patients with ADHD n (%) | ADHD diagnosed timing | |||
|---|---|---|---|---|---|
| Before n (%) | Simultaneously n (%) | After n (%) | |||
| Mental and behavioral disorders due to psychoactive substance use (F10–19) | 17962 | 7 (0.04) | 3 (42.9) | 0 (0) | 4 (57.1) |
| Bipolar affective disorder (F31) | 5481 | 69 (1.3) | 13 (18.8) | 18 (26.1) | 38 (55.1) |
| Depressive episode (F32) | 44168 | 283 (0.64) | 41 (14.5) | 89 (31.4) | 153 (54.1) |
| Phobic anxiety disorders (F40), Other anxiety (F41) | 33032 | 107 (0.3) | 17 (15.9) | 34 (31.2) | 56 (52.3) |
| Obsessive compulsive disorders (F42) | 861 | 4 (0.5) | 0 (0) | 0 (0) | 4 (100) |
| Eating disorders (F50), Symptoms and signs concerning food and fluid intake (R63) | 26585 | 28 (0.1) | 7 (25.0) | 0 (0) | 21 (75.0) |
| Specific developmental disorders of speech and language (F80), Specific developmental disorders of scholastic skills (F81) | 207 | 3 (1.4) | 1 (33.3) | 0 (0) | 2 (66.7) |
| Pervasive developmental disorders (F84) | 566 | 62 (11.0) | 6 (9.7) | 34 (54.8) | 22 (35.5) |
| Conduct disorders (F91) | 1 | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Tic disorders (F95) | 61 | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
ADHD, Attention-Deficit/Hyperactivity Disorder.
In this study, using large claims data, we established that 0.19% of working-age workers were diagnosed with ADHD after the diagnosis of one of the 10 typical comorbidities of ADHD. To the best of our knowledge, this is the first report on the timing of diagnosis of ADHD and its comorbidities in the Japanese working-age workers.
According to a report, the estimated suicide rate of patients with ADHD is 0.63–0.78% due to psychiatric conditions such as depression and conduct disorders.24) To alleviate symptoms of comorbidities associated with ADHD, it is important to diagnose and treat ADHD in acute disease stages.25,26) Patients with ADHD encounter challenges in their social lives and are highly predisposed to the development of psychiatric diseases.1,5,15) In general, therapy in early stages helps to prevent the worsening of psychiatric symptoms.27,28) Importantly, the presentation of psychiatric symptoms may be attributed to ADHD.8) Understanding and managing the core symptoms of ADHD and other psychiatric conditions as well as their timing of diagnosis is important.
In cohort 1, 0.19% of patients were diagnosed with ADHD after being diagnosed with typical comorbidities, using the earliest date as the primary endpoint. Especially, over 50% of patients were diagnosed with ADHD after the diagnosis of the following: obsessive-compulsive disorders, eating disorders/symptoms and signs concerning food and fluid intake, specific developmental disorders of speech and language/specific developmental disorders of scholastic skills, mental and behavioral disorders due to psychoactive substance use, bipolar affective disorder, depressive episode, and phobic anxiety disorders/other anxiety (Table 2, Fig. 2). Generally, over 80% of patients with ADHD have psychiatric comorbidities.15–17) Based on their background, 0.19% of working-age patients had any of the 10 typical psychiatric diseases possibly due to ADHD. This raises the need for physicians and pharmacists to consider earlier diagnoses of ADHD when dealing with psychiatric diseases in clinical settings.
The prevalence for ADHD is reported to be 1.65–7% in each study settings such as children, adolescents, working age population, or general adult population.2–7) In our study, we focused on the 10 typical diseases which are commonly observed as comorbidities of ADHD. Therefore, the number of patients diagnosed with ADHD was not large. One possible reason why we could not detect ADHD patients is that for patients with any of the 10 typical comorbidities with ADHD, it may be difficult continue to work (our study setting is at least 24 months within screening and observation periods). Therefore, we think our data are reliable for the above-mentioned population, such that the diagnoses were not very severe resulting in discontinuation of work.
LimitationsThis study has several limitations. First, we did not use date data of diagnosed timing for ADHD and the 10 typical psychiatric disease. This means that if a patient was assessed as being in the “simultaneous” diagnosed timing group, they could also potentially be included in the “before” or “after” groups because we used the diagnosed timing for “month” of 10 typical psychiatric diseases and ADHD. Second, we defined the 10 typical psychiatric diseases associated with ADHD solely using ICD 10 codes. This could potentially have overestimated these comorbidities in our study. Third, there were 235 patients who were diagnosed outside of the screening and observation periods established for this study before 12 months and after 11 months from the index month of the 10 typical psychiatric disorders. This means that our study could have potentially underestimated the proportion of ADHD patients in patients diagnosed with any of the 10 typical psychiatric diseases.
In conclusion, the timing of diagnosis of the 10 typical psychiatric comorbidities in working-age workers with ADHD was determined. Timely diagnosis and therapy for ADHD are warranted, especially in 0.19% of the patients who were diagnosed with ADHD within 12 months after diagnosis with a comorbidity, to alleviate the symptoms of ADHD and reduce the risk of developing ADHD-associated comorbidities. Our study results will be beneficial in improving the QOL and care for patients with ADHD.
KM (Showa University) and JMDC collaborate on other projects according to the joint research agreement; JMDC did not intervene in data implementation; MA received a travel fee from Otsuka Pharmaceutical to join a meeting held by them; KM received honorarium fees for presentations from JMDC, Abbvie, and Nippon-Kayaku and received a travel fee from Abbvie to join their conference; NH received honorarium fees for a presentation from Daiichi Sankyo; TN received honorarium fees for a presentation from Sumitomo; TakY received honorarium fees for a presentation from Sumitomo, Otsuka Pharmaceutical, Meiji Seika, and Yoshitomi-Yakuhin; MK received honorarium fees for presentations from Meiji Seika.
The Department of Hospital Pharmaceutics received a contracted research fee from Ono; The Department of Clinical Pharmacy Division of Clinical Research and Development received a contracted research fee for other research from Nippon-Kayaku; The Department of Hospital Pharmaceutics, School of Pharmacy, and Showa University received a research Grant from Nippon-Kayaku, Ono, Shionogi, Daiichi Sankyo, Eisai, Mochida, Taiho. The Department of Clinical Pharmacy Division of Clinical Research and Development and Showa University received other services for research from Ono.
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