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ADHD: a hidden comorbidity in adult psychiatric patients

ADHD: a hidden comorbidity in adult psychiatric patients Adult attention-deficit/hyperactivity disorder (aADHD) has recently been better recognized and treated in many European countries. In spite of this development, aADHD still features as a “hidden” comorbidity, often not diagnosed even in patients under psychiatric treatment for other psychiatric disorders. The aim of this study was to establish the prevalence rates of unrecognized aADHD in academic centers providing regular psychiatric services in the Czech Republic and Hungary. In a population of psychiatric in-and outpatients, Adult ADHD Self-Report Scale was administered. All positively and about half of the negatively screened subjects were clinically interviewed and the DSM diagnosis of ADHD was determined based on the symptom list and Conners’ Adult ADHD Rating Scale. The estimated point prevalence rate of unrecognized comorbid aADHD among psychiatric in-and out patients was 6.99% (95% lower CI: 5.11, 95% upper CI 8.86) according to the DSM- IV-TR criteria and 9.27% (95% lower CI: 7.13, 95% upper CI 11.40) according to the DSM-5 criteria. Current suicide risk was significantly associated with the presence of undiagnosed aADHD; however, life time suicide attempts, depression, dysthymia, alcohol and substance dependence, anxiety and stress related disorders were not. Further educational efforts are needed to improve the recognition and treatment of aADHD in adults Keywords ADHD · Adult ADHD · Comorbidity · Prevalence · Epidemiology Introduction DSM-IV-TR (American Psychiatric Association 2000) diag- nostic criteria and the rest is regarded as ‘ADHD in partial Attention-deficit/hyperactivity disorder (ADHD) is a neu- remission’ (Ramos-Quiroga et al. 2013). Typically, the most rodevelopmental disorder, characterized with persistent and frequent subtype of adult ADHD (aADHD) is predominantly developmentally inappropriate level of inattention and/or inattentive type, with associated disorganization, emotional hyperactivity and impulsivity, resulting in functional impair- dysregulation (Kooij et al. 2010). ment (Buitelaar et al. 2011). Approximately two-thirds of A meta-analysis reported a 2.5% prevalence of aADHD individuals diagnosed with ADHD early in their lives suffer based on pooled data of population-based studies (Simon from symptoms in adult age, as well; 15% of them meet full et al. 2009). Similar number (current DSM-IV-TR aADHD prevalence of 2.8%) has been recently reported in a rep- resentative WHO World Mental Health Survey across 20 countries (Fayyad et al. 2017). István Bitter and Pavel Mohr have contributed equally. Adult ADHD is often associated with negative outcome, * István Bitter as evidenced by impaired psychosocial functioning and low bitter.istvan@med.semmelweis-univ.hu quality of life, including poor academic and occupational performance, interpersonal relationships, driving skills, low Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary socioeconomic status, self-esteem, or high criminality rates (Kooij et al. 2010; Buitelaar et al. 2011). The estimated eco- National Institute of Mental Health, Klecany, Czech Republic nomic impact of aADHD in the US is $105–194 billion per Third Faculty of Medicine, Charles University in Prague, year, the highest proportion being attributed to productiv- Prague, Czech Republic ity and income loss, $87–137 billion (Doshi et al. 2012). Department of Psychiatry, University Hospital Olomouc Swedish register and population-based data suggest that any and Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic Vol.:(0123456789) 1 3 84 I. Bitter et al. drug treatment of aADHD may reduce criminality, serious other than ADHD, with capacity to sign informed consent traffic accidents, and even suicide rates (Lichtenstein et al. form in their native language. Exclusion criteria were history 2012; Chang et al. 2014; Chen et al. 2014). of major neurological disorders and diagnosis of the follow- However, the recognition of aADHD remains poor, which ing psychiatric disorders: schizophrenia, cognitive disorders is partly explained by the high rates of comorbidity, which (e.g., dementia). may make the diagnosis difficult (Asherson et  al. 2007, The study consisted of two phases: Phase I (Screening 2014). In general, psychiatric comorbidity rates in aADHD Phase), and Phase II (Interview Phase), described below in can be as high as 49% for any current and 89% for any past detail. DSM-IV-TR Axis I disorder, and 78.5% for at least one, and 45% for at least two DSM-IV-TR Axis II disorders (Jacob Phase I et al. 2007; Sobanski et al. 2007; Cumyn et al. 2009). Spe- cifically, compared with non-ADHD subjects, significantly During the Screening Phase, consecutively arriving and higher rates of comorbid major depression (MD), dysthymia, consenting patients entered the study on randomly selected bipolar disorder (BD), anxiety disorders, substance use dis- days. The number of participants screened during a day var- orders (SUD), personality disorders (PD) were consistently ied according to patients consent and availability. Approxi- reported in adults with ADHD (Jacob et al. 2007; Sobanski mately half of the negatively screened participants were et al. 2007; Cumyn et al. 2009; Asherson et al. 2014; Per- approached for to participation in the Interview Phase of roud et al. 2014). the study. All study subjects signed informed consent form In a complementary manner, some authors suggested prior to administration of any study procedure. A trained that undiagnosed aADHD could be a frequent comorbidity assistant distributed to the subjects the ADHD screener, in patients already in treatment for at least one psychiatric the Adult ADHD Self-Report Scale (ASRS). ASRS is an disorder other than ADHD (Rao and Place 2011; Ginsberg 18-item self-report scale, based on the symptom list of et al. 2014). In a recent cross-sectional study conducted in DSM-IV-TR, developed by the Workgroup on Adult ADHD psychiatric outpatient health care facilities in eight European in conjunction with the World Health Organization (WHO) countries, the prevalence of aADHD was estimated between (Kessler et al. 2007). Symptom frequency was measured on 14.2 and 19.0% (min and max values of 95% CIs of the a 5-point Likert scale. In the screening phase of the study, prevalence values based on different definitions) (Deberdt the 6-question, screener version of ASRS was applied. This et al. 2015). short version of ASRS was reported to have good sensitivity The primary objective of our study was to estimate the and specificity as well as predictive value for the diagnosis prevalence of undiagnosed aADHD in both inpatient and of aADHD (Kessler et al. 2005). All positively screened and outpatients of university psychiatric clinics providing “regu- about half of the negatively screened subjects were invited lar” care. The secondary objectives were: (1) to investigate to further participate in the study. the effect of different diagnostic criteria on prevalence esti- mates of aADHD assessed in Czech and Hungarian psychi- Phase II atric inpatient and outpatient samples, and (2) to estimate the rate of comorbidity with aADHD in patients already Consenting patients entered Phase II, the Interview Phase. diagnosed with another psychiatric disorder. During the clinical interview, in addition to demographic data and diagnosis of aADHD, other potential comorbid psychiatric disorders were assessed. Methods DSM‑IVTR sympt ‑ om list The study protocol was approved by the ethics commit- tees for the Department of Psychiatry and Psychotherapy, A structured clinical interview has been earlier developed Semmelweis University in Budapest, Hungary and for the by the authors, using the symptom list of ADHD in DSM- Prague Psychiatric Center/National Institute of Mental IV-TR, including functional impairment and onset criteria Health, Czech Republic. During the course of the study, a (i.e., whether some of the symptoms had caused problems third study site (second Czech site) was added, Psychiatric before the age of seven) as well (Bitter et al. 2010). The Clinic University Hospital in Olomouc, in order to increase interview is comprised of two sections. The first section subjects’ enrollment. The change was approved by the Eth- assessed the presence of ADHD in childhood and included ics Committee. 20 items: 18 symptoms, as well as functional impairment Eligible study subjects were males and females, age of and age of onset. The second section assessed the presence 18–60 years, currently undergoing inpatient or outpatient of aADHD based on the same items as in the first section psychiatric treatment for a DSM-IV-TR Axis I diagnosis (with the exclusion of age of onset, which has already been 1 3 ADHD: a hidden comorbidity in adult psychiatric patients 85 Table 1 Estimated prevalence ADHD DSM- ADHD ADHD ADHD DSM-5 rates adjusted for the sensitivity IV (full criteria) DSM-IV DSM-IV no (full criteria) and specificity of the screener Sx onset and for sex ratio (1:1) for the four diagnostic groups defined Estimated prevalence % 6.99 13.41 9.18 9.27 in our study SE for the estimated prevalence 0.96 0.13 0.11 0.11 95% lower CI for the estimated prevalence 5.11 10.90 7.06 7.13 95% upper CI for the estimated prevalence 8.86 15.92 11.31 11.40 Total number of patients is based on the group of positively screened subjects. Differences in total number of patients is explained by missing data Table 2 Proportion of DSM-IV ADHD “yes” and “no” diagnoses associated with the most frequent current “main” (comorbid) psychiatric dis- orders and current suicide risk Main comorbid psychiatric disorder (MCPD) (MCPD/total number of In DSM-IV ADHD In DSM-IV ADHD Chi-square available patients) NO (n) % YES (n) % DF Value P Depression (188/438) (171) 42.86 (17) 43.59 1 0.01 0.93 Suicide risk current (38/433) (10) 54.43 (28) 73.68 1 5.21 0.02 Alcohol dependence (65/433) (59) 14.97 (6) 15.38 1 0.00 0.94 Psychoactive substance dependence (other than alcohol) (51/393) (47) 13.06 (4) 12.12 1 0.02 0.88 Anorexia (13/432) (13) 3.31 (0) 0 1 1.33 0.25 Anxiety and stress related disorders* (265/438) (239) 59.90 (26) 66.67 1 0.68 0.41 *Generalized anxiety disorder, panic disorder, agoraphobia, social phobia, obsessive–compulsive disorder, posttraumatic stress disorder; none of the listed disorders yielded significant Chi-square results separately collected in the first section); functional impairment (yes/ age, gender, years of education, type of education, marital no) was established based on whether the symptoms were status, current DSM-IV-TR Axis I diagnosis, psychiatric present and caused problems during the past half a year. and medical history, family history, medications taken on a regular basis, smoking status, handedness. Clinical interview During the clinical interview, the interviewer had 20–30 min Conners’ adult ADHD rating scale (CAARS) to collect relevant information about the presence aADHD. The type of information needed to be gathered was the same The CAARS 66 item self-report version (CAARS-S:L) for all the participants, but the interview was conducted in developed by Conners et  al. (1999) was used. CAARS an open-ended fashion, while the interviewers were making includes four factor-derived subscales (inattention/mem- detailed notes. The following issues had to be addressed: ory problems, hyperactivity/restlessness, impulsivity/ complications during pregnancy and delivery; develop- emotional lability, problems with self-concept) and three mental deviations; family background (relationship with DSM-IV-TR ADHD Subscales: DSM-IV-TR Inattentive parents, siblings, brief family history); preschool nursing Symptoms, DSM-IV-TR Hyperactive-Impulsive Symp- (problems with the other children, problems with the pre- toms, DSM-IV-TR Total ADHD Symptoms), the ADHD school teachers, adjustment problems); school years (studies, Index and the Inconsistency Index. Items are rated on a 4 behavior, relationship with students/teachers); jobs (conflicts point scale (0–3). with colleagues/supervisors, frequent job and/or workplace changes); relationships. MINI‑PLUS 5.0 structured interview Demographic and clinical characteristics The validated Czech and Hungarian versions of MINI- The following items were recorded and included in the PLUS structured interview (Balázs et al. 1998; Sheehan assessment of demographic and clinical characteristics: et al. 1998) were applied for the assessment of lifetime and current DSM-IV-TR Axis I psychiatric disorders. 1 3 86 I. Bitter et al. and ‘non-interviewed’ subsamples are presented in Fig. 1. Diagnosis of aADHD Figure 1 also describes the row prevalence rates of the four predefined groups as listed above: Based on the documentation of the clinical interview, the study team decided whether the participant meets the criteria 1. ‘ADHD_DSM-IV-TR’ diagnostic group: based on the for the clinical diagnosis of adult ADHD. Based on previous aADHD prevalence studies (Bitter et al. 2010), modified full set of DSM-IV-TR criteria for both childhood and aADHD. diagnostic criteria were also applied to investigate the effect of diagnostic criteria on the prevalence estimates. Below, we 2. ‘ADHD_No-onset’ group: based on DSM-IV-TR criteria for both childhood and aADHD without the criterion of present three modified criteria based on their relation to the DSM-IV-TR criteria and a fourth criterion based on DSM-5 onset. 3. ‘ADHD_Symptoms-only’ group: based on DSM-IV-TR criteria (American Psychiatric Association 2013). symptom criterion only (6 symptoms had to be present out of the 9 symptoms of either inattention or hyper- 1. ‘ADHD_DSM-IV-TR’ diagnostic group: based on the full set of DSM-IV-TR criteria for both childhood and activity/impulsivity, or both) for both childhood and aADHD. aADHD (combined, or inattentive, or hyperactive/ impulsive type) with supporting information based on 4. ‘ADHD_DSM-5’ diagnostic group: based on the full set of DSM-5 criteria for both childhood and aADHD. the clinical interview. 2. ‘ADHD_No-onset’ group: based on DSM-IV-TR criteria for both childhood and aADHD (combined or inattentive or hyperactive/impulsive type), excluding onset crite- Discussion rion. 3. ‘ADHD_Symptoms-only’ group: based on DSM-IV-TR Our data support earlier n fi dings that aADHD often remains an undiagnosed and consequently untreated disorder even symptom criterion only (6 symptoms had to be present out of the 9 symptoms of either inattention or hyper- in patients under treatment for another psychiatric disor- der (Deberdt et al. 2015). While the estimated point preva- activity/impulsivity, or both) for both childhood and aADHD. lence rates (adjusted for age and sex and for the sensitivity and specificity of the screener) of undiagnosed aADHD in 4. ‘ADHD_DSM-5’ diagnostic group: based on the full set of DSM-5 criteria for both childhood and aADHD with the two Czech and the one Hungarian psychiatric centers were found to be lower than in the cited European study supporting information based on the clinical interview. The study protocol was written prior to the publication (Deberdt et al. 2015), they are still high. The European study reported row rates “applying DSM-IV-TR-TR or DSM-5 cri- of DSM-5. DSM-5 criteria were added to the protocol after its publication. teria, 15.8% (95% confidence interval [CI] 14.2–17.4%) or 17.4% (95% CI 15.7–19.0%) of patients were diagnosed with Statistical analysis ADHD, respectively”, while we report adjusted prevalence estimations for the DSM-IV-TR group 6.99% (95% confi- The Statistical Analysis System for Windows (version 9.1; dence interval [CI] 5.11%–8.86%) and for the DSM-5 group 9.27% (95% confidence interval [CI] 7.13%–11.40%). The SAS Institute, Cary, NC) was used for statistical analyses. All statistical analyses used the alpha error level of 0.05 strength of this study is that in order to improve case iden- tification in addition to ASRS further methods were used, (two-sided) and 95% confidence intervals. In order to deter - mine the true population prevalence, the specificity and sen- including a semistructured clinical interview, the Conners’ Adult ADHD Rating Scale (CAARS) and the MINI-PLUS sitivity of the screening test was taken into consideration. 5.0 Structured interview. The European study found 10% higher rates using DSM-5 criteria as compared to DSM-IV- Results TR criteria, while our study shows a 32.6% higher rate when using DSM-5 criteria as compared to DSM-IV-TR criteria. Seven hundred and sixteen patients were included in the These results are similar to those of Vitola et al. (2017), who found that “The use of the DSM-5 criteria results in a higher screening phase (Budapest: 580, Prague: 136) between 7th July, 2012 and 26th June, 2014. Eight patients fulfilled one prevalence of ADHD when compared to those obtained by DSM-IV.” of the exclusion criteria; thus, we report data on 708 patients (Tables  1, 2). Patients disposition including basic demo- We found no significant differences between the sizes of the subgroups with or without DSM-IV-TR aADHD in the graphic data and the ASRS mean scores of the study sample, as well as the ‘positively screened’, ‘interviewed’ and ‘not- investigated diagnostic groups; however, there are statisti- cally significant differences regarding current suicide risk. interviewed’ and the ‘negatively screened’ ‘interviewed’ 1 3 ADHD: a hidden comorbidity in adult psychiatric patients 87 Legend: Total N=708 ADHDyes = Meets ALL DSM-IV-TR criteria of ADHD ADHDyesSx = Meets only the DSM-IV symptom criteria of in DataBase ADHD Prague and Budapest center 1= 572 ADHDyesNoOnset = Meets DSM-IV criteria excluding onset criteria ADHDdsm5Yes = Meets DSM-5 criteria of ADHD center 2= 136 test_done=708 age=38.5 female=65% ASRS negave ASRS posive N=422 N=286 422/708 286/708 age=39.2 age= 38.6 female=63% female= 67% Detailed Test Detailed Test Detailed Test Detailed Test Baery:YES Baery:NO Baery:YES Baery:NO 247/286 39/286 205/422 217/422 86% 14% 49% 51% N= 247 N=39 N= 205 N=217 age= 38.2 age= 41.2 age= 38.9 age= 39.4 female= 69% female= 60% female= 62% female=63% ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD dsm5 dsm5 yesNOo yesNOo dsm5 dsm5 No yesNOon yes No yesSx yesSxNO yesNOon nset nset NO yes yesSxNO yesSx NO set NO yes yes 196/205 216/247 setNO 31/247 58/247 189/247 206/247 9/205 41/247 14/205 191/205 206/247 9/205 196/205 9/205 41/247 96% 196/205 13% 87% 23% 77% 17% 83% 4% 7% 93% 83% 4% 96% 4% 17% N= 196 N=216 96% N=31 N=58 N=189 N= 41 N= 206 N= 9 N= 14 N= 191 N= 206 N= 9 N= 196 N=9 N=41 age= age= N= 196 age= age=36. age=38.6 age=33.3 age=35. age=38. age=34.2 age=39.3 age=38.6 39.2 age=33.2 age=39.2 38.8 age=33.2 34.1 8 age=36.3 age=39.2 8 7 female= female= female= female= female= female= female= female= female= female= female= female= female= female=5 female= female= 55% 64% 43% 71% 63% 55% 69% 56% 62% 6% 71% 63% 63% 65% 56% 71% Fig. 1 Study flowchart, basic demographics and raw prevalence rates by patient disposition This finding is in line with previous studies highlighting the an addiction” (Ohlmeier et al. 2008). Although the pres- positive association between ADHD and suicidality (Bal- ence of comorbid psychiatric conditions with ADHD com- azs and Kereszteny 2017). The presence of aADHD may plicates the treatment and results in more severe dysfunction be associated with more severe symptoms of the comorbid and impairment (Biederman 2004), the background of the psychiatric disorders; however, no data were collected in observed high rate of psychiatric comorbidity in ADHD is this study to characterize the severity of comorbid disorders. still an open question. (Sonuga-Barke 2005; Spencer et al. In case no childhood onset of ADHD can be identified, 2007; Biederman et al. 2008; Halmoy et al. 2010). clinicians should carefully assess impairment, psychiatric Developmental disturbances (Sonuga-Barke 2005) as history, and substance use before treating potential late-onset well as the role of overlapping symptoms and possible case cases. False positive late-onset ADHD cases are common over-identification (Halmoy et al. 2010) have already been without careful assessment (Sibley et al. 2018). However, suggested in the literature. Gender differences were consist- as Matte et al. (2015) pointed out about the DSM-5 adult ently reported in the prevalence of comorbid conditions in ADHD criteria, “The proposed new impulsivity symptoms adults with ADHD. Specifically, SUD (alcohol use), conduct for adults do not improve ADHD diagnosis enough to over- disorder (CD), antisocial PD were more prevalent among come potential negative effects of changing the criteria. males, while MD, dysthymia, and anxiety disorders were However, fewer symptoms than the six-of-nine threshold more prevalent among females with ADHD in the majority required by DSM-IV provided the best cutoff point for iden- of the studies (Biederman et al. 1993; Sobanski et al. 2007; tifying adults who are impaired.” Sprafkin et al. 2007; Wilens et al. 2009). Nonetheless, Bie- The proper diagnosis and treatment of comorbid ADHD derman (2004) reported on no moderating effect of gender and other psychiatric disorders is important, since they may on psychiatric comorbidity with ADHD in adults. lead to higher rates of unfavorable outcomes. Available evi- Other possible moderating factors for the rate of comor- dence suggests that ADHD is associated with earlier onset bidity in/with ADHD could be the severity of ADHD and of comorbid disorders, such as alcoholism and “ADHD in the diagnostic criteria used for ADHD (Bitter et al. 2010). combination with a comorbid disorder (depression, anxiety This has been supported by the findings indicating that disorder, etc.) additionally increases the risk of developing ADHD symptom severity is signic fi antly correlated with the 1 3 88 I. Bitter et al. American Psychiatric Association (2013) Diagnostic and statistical occurrence of lifetime depressive episodes in both males and manual of mental disorders, 5h edn. American Psychiatric Asso- females (Simon et al. 2013). ciation, Arlington Our data underline the need for better training for the Asherson P, Chen W, Craddock B, Taylor E (2007) Adult attention- recognition of adult ADHD comorbid with substance use deficit hyperactivity disorder: recognition and treatment in general adult psychiatry. Br J Psychiatry 190:4–5 and other mental disorders. Asherson P, Young AH, Eich-Höchli D, Moran P, Porsdal V, Deberdt W (2014) Differential diagnosis, comorbidity, and treatment of attention-deficit/hyperactivity disorder in relation to bipolar disorder or borderline personality disorder in adults. Curr Med Limitations Res Opin 8:1657–1672 Balazs J, Kereszteny A (2017) Attention-deficit/hyperactivity dis- The major limitation of this study is its cross-sec- order and suicide: a systematic review. World J Psychiatry tional design, which does not permit to establish causal 7:44–59 Balázs J, Bitter I, Hideg K, Vitrai J (1998) A MINI és a MINI Plusz relationships. kérdõív magyar nyelvû változatának kidolgozása. (Development of the Hungarian version of the MINI and MINI Plus question- Acknowledgements Open access funding provided by Semmelweis naires). Psychiatria Hung 13:160–168 University (SE). The authors would like to thank Drs. Anna Angyalosi Biederman J (2004) Impact of comorbidity in adults with attention- and Zuzana Kratochvílová, Ágnes Bán Gérecz, Berta Hamza Erdélyi, deficit/hyperactivity disorder. J Clin Psychiatry 65(Suppl 3):3–7 Enikő Németh and Dóra Uram for their contribution to the data collec- Biederman J, Faraone SV, Spencer T, Wilens T, Norman D, Lapey KA tion and Ms. Márta Kovács for the logistical support. et al (1993) Patterns of psychiatric comorbidity, cognition, psy- chosocial functioning in adults with attention deficit hyperactivity Funding E. Lilly supported part of this study providing an Investiga- disorder. Am J Psychiatry 150:1792–1798 tors Initiated Grant to Drs. Bitter and Mohr. The Sponsor reviewed the Biederman J, Ball SW, Monuteaux MC, Mick E, Spencer TJ, McCreary proposal and received a copy of the submitted manuscript; however, M et al (2008) New insights into the comorbidity between ADHD they had no role in the planning and implementation of the study, draft- and major depression in adolescent and young adult females. J Am ing and submission of the manuscript or in any other parts of this study. Acad Child Adol Psychiatry 47:426–434 Bitter I, Simon V, Balint S, Meszaros A, Czobor P (2010) How do different diagnostic criteria, age and gender affect the prevalence Compliance with ethical standards of attention deficit hyperactivity disorder in adults? An epide- miological study in a Hungarian community sample. Eur Arch Conflict of interest The authors declare that beyond the above dis- Psychiatry Clin Neurosci 260:287–296 closed funding have no conflict of interest. Buitelaar JK, Kan CC, Asherson P (2011) ADHD in adults. Charac- terization, diagnosis, and treatment. Cambridge University Press, Statement on human rights All procedures performed in studies involv- New York ing human participants were in accordance with the ethical standards of Chang Z, Lichtenstein P, D’Onofrio BM, Sjölander A, Larsson H the institutional and/or national research committee and with the 1964 (2014) Serious transport accidents in adults with attention-deficit/ Helsinki declaration and its later amendments or comparable ethical hyperactivity disorder and the effect of medication: a population- standards. The protocol and the patient information and informed con- based study. JAMA Psychiatry 71:319–325 sent forms of this non-interventional study were approved by the ethics Chen Q, Sjölander A, Runeson B, D’Onofrio BM, Lichtenstein P, committees for the Department of Psychiatry and Psychotherapy, Sem- Larsson H (2014) Drug treatment for attention-deficit/hyperac- melweis University in Budapest, Hungary and for the Prague Psychiatric tivity disorder and suicidal behaviour: register based study. BMJ Center/National Institute of Mental Health, Czech Republic. During the 348:g3769. https ://doi.org/10.1136/bmj.g3769 course of the study, a third study site (second Czech site) was added, Conners CK, Erhardt D, Sparrow EP (1999) Conners’ Adult ADHD Psychiatric Clinic University Hospital in Olomouc, in order to increase Rating Scales (CAARS). Multi-Health Systems Inc, North subjects’ enrollment. The change was approved by the Ethics Committee. 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Curr Med Res Opin 29:1093–1104 1 3 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png ADHD Attention Deficit and Hyperactivity Disorders Springer Journals

ADHD: a hidden comorbidity in adult psychiatric patients

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Springer Journals
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Copyright © 2019 by The Author(s)
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Medicine & Public Health; Psychiatry
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1866-6116
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10.1007/s12402-019-00285-9
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Abstract

Adult attention-deficit/hyperactivity disorder (aADHD) has recently been better recognized and treated in many European countries. In spite of this development, aADHD still features as a “hidden” comorbidity, often not diagnosed even in patients under psychiatric treatment for other psychiatric disorders. The aim of this study was to establish the prevalence rates of unrecognized aADHD in academic centers providing regular psychiatric services in the Czech Republic and Hungary. In a population of psychiatric in-and outpatients, Adult ADHD Self-Report Scale was administered. All positively and about half of the negatively screened subjects were clinically interviewed and the DSM diagnosis of ADHD was determined based on the symptom list and Conners’ Adult ADHD Rating Scale. The estimated point prevalence rate of unrecognized comorbid aADHD among psychiatric in-and out patients was 6.99% (95% lower CI: 5.11, 95% upper CI 8.86) according to the DSM- IV-TR criteria and 9.27% (95% lower CI: 7.13, 95% upper CI 11.40) according to the DSM-5 criteria. Current suicide risk was significantly associated with the presence of undiagnosed aADHD; however, life time suicide attempts, depression, dysthymia, alcohol and substance dependence, anxiety and stress related disorders were not. Further educational efforts are needed to improve the recognition and treatment of aADHD in adults Keywords ADHD · Adult ADHD · Comorbidity · Prevalence · Epidemiology Introduction DSM-IV-TR (American Psychiatric Association 2000) diag- nostic criteria and the rest is regarded as ‘ADHD in partial Attention-deficit/hyperactivity disorder (ADHD) is a neu- remission’ (Ramos-Quiroga et al. 2013). Typically, the most rodevelopmental disorder, characterized with persistent and frequent subtype of adult ADHD (aADHD) is predominantly developmentally inappropriate level of inattention and/or inattentive type, with associated disorganization, emotional hyperactivity and impulsivity, resulting in functional impair- dysregulation (Kooij et al. 2010). ment (Buitelaar et al. 2011). Approximately two-thirds of A meta-analysis reported a 2.5% prevalence of aADHD individuals diagnosed with ADHD early in their lives suffer based on pooled data of population-based studies (Simon from symptoms in adult age, as well; 15% of them meet full et al. 2009). Similar number (current DSM-IV-TR aADHD prevalence of 2.8%) has been recently reported in a rep- resentative WHO World Mental Health Survey across 20 countries (Fayyad et al. 2017). István Bitter and Pavel Mohr have contributed equally. Adult ADHD is often associated with negative outcome, * István Bitter as evidenced by impaired psychosocial functioning and low bitter.istvan@med.semmelweis-univ.hu quality of life, including poor academic and occupational performance, interpersonal relationships, driving skills, low Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary socioeconomic status, self-esteem, or high criminality rates (Kooij et al. 2010; Buitelaar et al. 2011). The estimated eco- National Institute of Mental Health, Klecany, Czech Republic nomic impact of aADHD in the US is $105–194 billion per Third Faculty of Medicine, Charles University in Prague, year, the highest proportion being attributed to productiv- Prague, Czech Republic ity and income loss, $87–137 billion (Doshi et al. 2012). Department of Psychiatry, University Hospital Olomouc Swedish register and population-based data suggest that any and Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic Vol.:(0123456789) 1 3 84 I. Bitter et al. drug treatment of aADHD may reduce criminality, serious other than ADHD, with capacity to sign informed consent traffic accidents, and even suicide rates (Lichtenstein et al. form in their native language. Exclusion criteria were history 2012; Chang et al. 2014; Chen et al. 2014). of major neurological disorders and diagnosis of the follow- However, the recognition of aADHD remains poor, which ing psychiatric disorders: schizophrenia, cognitive disorders is partly explained by the high rates of comorbidity, which (e.g., dementia). may make the diagnosis difficult (Asherson et  al. 2007, The study consisted of two phases: Phase I (Screening 2014). In general, psychiatric comorbidity rates in aADHD Phase), and Phase II (Interview Phase), described below in can be as high as 49% for any current and 89% for any past detail. DSM-IV-TR Axis I disorder, and 78.5% for at least one, and 45% for at least two DSM-IV-TR Axis II disorders (Jacob Phase I et al. 2007; Sobanski et al. 2007; Cumyn et al. 2009). Spe- cifically, compared with non-ADHD subjects, significantly During the Screening Phase, consecutively arriving and higher rates of comorbid major depression (MD), dysthymia, consenting patients entered the study on randomly selected bipolar disorder (BD), anxiety disorders, substance use dis- days. The number of participants screened during a day var- orders (SUD), personality disorders (PD) were consistently ied according to patients consent and availability. Approxi- reported in adults with ADHD (Jacob et al. 2007; Sobanski mately half of the negatively screened participants were et al. 2007; Cumyn et al. 2009; Asherson et al. 2014; Per- approached for to participation in the Interview Phase of roud et al. 2014). the study. All study subjects signed informed consent form In a complementary manner, some authors suggested prior to administration of any study procedure. A trained that undiagnosed aADHD could be a frequent comorbidity assistant distributed to the subjects the ADHD screener, in patients already in treatment for at least one psychiatric the Adult ADHD Self-Report Scale (ASRS). ASRS is an disorder other than ADHD (Rao and Place 2011; Ginsberg 18-item self-report scale, based on the symptom list of et al. 2014). In a recent cross-sectional study conducted in DSM-IV-TR, developed by the Workgroup on Adult ADHD psychiatric outpatient health care facilities in eight European in conjunction with the World Health Organization (WHO) countries, the prevalence of aADHD was estimated between (Kessler et al. 2007). Symptom frequency was measured on 14.2 and 19.0% (min and max values of 95% CIs of the a 5-point Likert scale. In the screening phase of the study, prevalence values based on different definitions) (Deberdt the 6-question, screener version of ASRS was applied. This et al. 2015). short version of ASRS was reported to have good sensitivity The primary objective of our study was to estimate the and specificity as well as predictive value for the diagnosis prevalence of undiagnosed aADHD in both inpatient and of aADHD (Kessler et al. 2005). All positively screened and outpatients of university psychiatric clinics providing “regu- about half of the negatively screened subjects were invited lar” care. The secondary objectives were: (1) to investigate to further participate in the study. the effect of different diagnostic criteria on prevalence esti- mates of aADHD assessed in Czech and Hungarian psychi- Phase II atric inpatient and outpatient samples, and (2) to estimate the rate of comorbidity with aADHD in patients already Consenting patients entered Phase II, the Interview Phase. diagnosed with another psychiatric disorder. During the clinical interview, in addition to demographic data and diagnosis of aADHD, other potential comorbid psychiatric disorders were assessed. Methods DSM‑IVTR sympt ‑ om list The study protocol was approved by the ethics commit- tees for the Department of Psychiatry and Psychotherapy, A structured clinical interview has been earlier developed Semmelweis University in Budapest, Hungary and for the by the authors, using the symptom list of ADHD in DSM- Prague Psychiatric Center/National Institute of Mental IV-TR, including functional impairment and onset criteria Health, Czech Republic. During the course of the study, a (i.e., whether some of the symptoms had caused problems third study site (second Czech site) was added, Psychiatric before the age of seven) as well (Bitter et al. 2010). The Clinic University Hospital in Olomouc, in order to increase interview is comprised of two sections. The first section subjects’ enrollment. The change was approved by the Eth- assessed the presence of ADHD in childhood and included ics Committee. 20 items: 18 symptoms, as well as functional impairment Eligible study subjects were males and females, age of and age of onset. The second section assessed the presence 18–60 years, currently undergoing inpatient or outpatient of aADHD based on the same items as in the first section psychiatric treatment for a DSM-IV-TR Axis I diagnosis (with the exclusion of age of onset, which has already been 1 3 ADHD: a hidden comorbidity in adult psychiatric patients 85 Table 1 Estimated prevalence ADHD DSM- ADHD ADHD ADHD DSM-5 rates adjusted for the sensitivity IV (full criteria) DSM-IV DSM-IV no (full criteria) and specificity of the screener Sx onset and for sex ratio (1:1) for the four diagnostic groups defined Estimated prevalence % 6.99 13.41 9.18 9.27 in our study SE for the estimated prevalence 0.96 0.13 0.11 0.11 95% lower CI for the estimated prevalence 5.11 10.90 7.06 7.13 95% upper CI for the estimated prevalence 8.86 15.92 11.31 11.40 Total number of patients is based on the group of positively screened subjects. Differences in total number of patients is explained by missing data Table 2 Proportion of DSM-IV ADHD “yes” and “no” diagnoses associated with the most frequent current “main” (comorbid) psychiatric dis- orders and current suicide risk Main comorbid psychiatric disorder (MCPD) (MCPD/total number of In DSM-IV ADHD In DSM-IV ADHD Chi-square available patients) NO (n) % YES (n) % DF Value P Depression (188/438) (171) 42.86 (17) 43.59 1 0.01 0.93 Suicide risk current (38/433) (10) 54.43 (28) 73.68 1 5.21 0.02 Alcohol dependence (65/433) (59) 14.97 (6) 15.38 1 0.00 0.94 Psychoactive substance dependence (other than alcohol) (51/393) (47) 13.06 (4) 12.12 1 0.02 0.88 Anorexia (13/432) (13) 3.31 (0) 0 1 1.33 0.25 Anxiety and stress related disorders* (265/438) (239) 59.90 (26) 66.67 1 0.68 0.41 *Generalized anxiety disorder, panic disorder, agoraphobia, social phobia, obsessive–compulsive disorder, posttraumatic stress disorder; none of the listed disorders yielded significant Chi-square results separately collected in the first section); functional impairment (yes/ age, gender, years of education, type of education, marital no) was established based on whether the symptoms were status, current DSM-IV-TR Axis I diagnosis, psychiatric present and caused problems during the past half a year. and medical history, family history, medications taken on a regular basis, smoking status, handedness. Clinical interview During the clinical interview, the interviewer had 20–30 min Conners’ adult ADHD rating scale (CAARS) to collect relevant information about the presence aADHD. The type of information needed to be gathered was the same The CAARS 66 item self-report version (CAARS-S:L) for all the participants, but the interview was conducted in developed by Conners et  al. (1999) was used. CAARS an open-ended fashion, while the interviewers were making includes four factor-derived subscales (inattention/mem- detailed notes. The following issues had to be addressed: ory problems, hyperactivity/restlessness, impulsivity/ complications during pregnancy and delivery; develop- emotional lability, problems with self-concept) and three mental deviations; family background (relationship with DSM-IV-TR ADHD Subscales: DSM-IV-TR Inattentive parents, siblings, brief family history); preschool nursing Symptoms, DSM-IV-TR Hyperactive-Impulsive Symp- (problems with the other children, problems with the pre- toms, DSM-IV-TR Total ADHD Symptoms), the ADHD school teachers, adjustment problems); school years (studies, Index and the Inconsistency Index. Items are rated on a 4 behavior, relationship with students/teachers); jobs (conflicts point scale (0–3). with colleagues/supervisors, frequent job and/or workplace changes); relationships. MINI‑PLUS 5.0 structured interview Demographic and clinical characteristics The validated Czech and Hungarian versions of MINI- The following items were recorded and included in the PLUS structured interview (Balázs et al. 1998; Sheehan assessment of demographic and clinical characteristics: et al. 1998) were applied for the assessment of lifetime and current DSM-IV-TR Axis I psychiatric disorders. 1 3 86 I. Bitter et al. and ‘non-interviewed’ subsamples are presented in Fig. 1. Diagnosis of aADHD Figure 1 also describes the row prevalence rates of the four predefined groups as listed above: Based on the documentation of the clinical interview, the study team decided whether the participant meets the criteria 1. ‘ADHD_DSM-IV-TR’ diagnostic group: based on the for the clinical diagnosis of adult ADHD. Based on previous aADHD prevalence studies (Bitter et al. 2010), modified full set of DSM-IV-TR criteria for both childhood and aADHD. diagnostic criteria were also applied to investigate the effect of diagnostic criteria on the prevalence estimates. Below, we 2. ‘ADHD_No-onset’ group: based on DSM-IV-TR criteria for both childhood and aADHD without the criterion of present three modified criteria based on their relation to the DSM-IV-TR criteria and a fourth criterion based on DSM-5 onset. 3. ‘ADHD_Symptoms-only’ group: based on DSM-IV-TR criteria (American Psychiatric Association 2013). symptom criterion only (6 symptoms had to be present out of the 9 symptoms of either inattention or hyper- 1. ‘ADHD_DSM-IV-TR’ diagnostic group: based on the full set of DSM-IV-TR criteria for both childhood and activity/impulsivity, or both) for both childhood and aADHD. aADHD (combined, or inattentive, or hyperactive/ impulsive type) with supporting information based on 4. ‘ADHD_DSM-5’ diagnostic group: based on the full set of DSM-5 criteria for both childhood and aADHD. the clinical interview. 2. ‘ADHD_No-onset’ group: based on DSM-IV-TR criteria for both childhood and aADHD (combined or inattentive or hyperactive/impulsive type), excluding onset crite- Discussion rion. 3. ‘ADHD_Symptoms-only’ group: based on DSM-IV-TR Our data support earlier n fi dings that aADHD often remains an undiagnosed and consequently untreated disorder even symptom criterion only (6 symptoms had to be present out of the 9 symptoms of either inattention or hyper- in patients under treatment for another psychiatric disor- der (Deberdt et al. 2015). While the estimated point preva- activity/impulsivity, or both) for both childhood and aADHD. lence rates (adjusted for age and sex and for the sensitivity and specificity of the screener) of undiagnosed aADHD in 4. ‘ADHD_DSM-5’ diagnostic group: based on the full set of DSM-5 criteria for both childhood and aADHD with the two Czech and the one Hungarian psychiatric centers were found to be lower than in the cited European study supporting information based on the clinical interview. The study protocol was written prior to the publication (Deberdt et al. 2015), they are still high. The European study reported row rates “applying DSM-IV-TR-TR or DSM-5 cri- of DSM-5. DSM-5 criteria were added to the protocol after its publication. teria, 15.8% (95% confidence interval [CI] 14.2–17.4%) or 17.4% (95% CI 15.7–19.0%) of patients were diagnosed with Statistical analysis ADHD, respectively”, while we report adjusted prevalence estimations for the DSM-IV-TR group 6.99% (95% confi- The Statistical Analysis System for Windows (version 9.1; dence interval [CI] 5.11%–8.86%) and for the DSM-5 group 9.27% (95% confidence interval [CI] 7.13%–11.40%). The SAS Institute, Cary, NC) was used for statistical analyses. All statistical analyses used the alpha error level of 0.05 strength of this study is that in order to improve case iden- tification in addition to ASRS further methods were used, (two-sided) and 95% confidence intervals. In order to deter - mine the true population prevalence, the specificity and sen- including a semistructured clinical interview, the Conners’ Adult ADHD Rating Scale (CAARS) and the MINI-PLUS sitivity of the screening test was taken into consideration. 5.0 Structured interview. The European study found 10% higher rates using DSM-5 criteria as compared to DSM-IV- Results TR criteria, while our study shows a 32.6% higher rate when using DSM-5 criteria as compared to DSM-IV-TR criteria. Seven hundred and sixteen patients were included in the These results are similar to those of Vitola et al. (2017), who found that “The use of the DSM-5 criteria results in a higher screening phase (Budapest: 580, Prague: 136) between 7th July, 2012 and 26th June, 2014. Eight patients fulfilled one prevalence of ADHD when compared to those obtained by DSM-IV.” of the exclusion criteria; thus, we report data on 708 patients (Tables  1, 2). Patients disposition including basic demo- We found no significant differences between the sizes of the subgroups with or without DSM-IV-TR aADHD in the graphic data and the ASRS mean scores of the study sample, as well as the ‘positively screened’, ‘interviewed’ and ‘not- investigated diagnostic groups; however, there are statisti- cally significant differences regarding current suicide risk. interviewed’ and the ‘negatively screened’ ‘interviewed’ 1 3 ADHD: a hidden comorbidity in adult psychiatric patients 87 Legend: Total N=708 ADHDyes = Meets ALL DSM-IV-TR criteria of ADHD ADHDyesSx = Meets only the DSM-IV symptom criteria of in DataBase ADHD Prague and Budapest center 1= 572 ADHDyesNoOnset = Meets DSM-IV criteria excluding onset criteria ADHDdsm5Yes = Meets DSM-5 criteria of ADHD center 2= 136 test_done=708 age=38.5 female=65% ASRS negave ASRS posive N=422 N=286 422/708 286/708 age=39.2 age= 38.6 female=63% female= 67% Detailed Test Detailed Test Detailed Test Detailed Test Baery:YES Baery:NO Baery:YES Baery:NO 247/286 39/286 205/422 217/422 86% 14% 49% 51% N= 247 N=39 N= 205 N=217 age= 38.2 age= 41.2 age= 38.9 age= 39.4 female= 69% female= 60% female= 62% female=63% ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD ADHD dsm5 dsm5 yesNOo yesNOo dsm5 dsm5 No yesNOon yes No yesSx yesSxNO yesNOon nset nset NO yes yesSxNO yesSx NO set NO yes yes 196/205 216/247 setNO 31/247 58/247 189/247 206/247 9/205 41/247 14/205 191/205 206/247 9/205 196/205 9/205 41/247 96% 196/205 13% 87% 23% 77% 17% 83% 4% 7% 93% 83% 4% 96% 4% 17% N= 196 N=216 96% N=31 N=58 N=189 N= 41 N= 206 N= 9 N= 14 N= 191 N= 206 N= 9 N= 196 N=9 N=41 age= age= N= 196 age= age=36. age=38.6 age=33.3 age=35. age=38. age=34.2 age=39.3 age=38.6 39.2 age=33.2 age=39.2 38.8 age=33.2 34.1 8 age=36.3 age=39.2 8 7 female= female= female= female= female= female= female= female= female= female= female= female= female= female=5 female= female= 55% 64% 43% 71% 63% 55% 69% 56% 62% 6% 71% 63% 63% 65% 56% 71% Fig. 1 Study flowchart, basic demographics and raw prevalence rates by patient disposition This finding is in line with previous studies highlighting the an addiction” (Ohlmeier et al. 2008). Although the pres- positive association between ADHD and suicidality (Bal- ence of comorbid psychiatric conditions with ADHD com- azs and Kereszteny 2017). The presence of aADHD may plicates the treatment and results in more severe dysfunction be associated with more severe symptoms of the comorbid and impairment (Biederman 2004), the background of the psychiatric disorders; however, no data were collected in observed high rate of psychiatric comorbidity in ADHD is this study to characterize the severity of comorbid disorders. still an open question. (Sonuga-Barke 2005; Spencer et al. In case no childhood onset of ADHD can be identified, 2007; Biederman et al. 2008; Halmoy et al. 2010). clinicians should carefully assess impairment, psychiatric Developmental disturbances (Sonuga-Barke 2005) as history, and substance use before treating potential late-onset well as the role of overlapping symptoms and possible case cases. False positive late-onset ADHD cases are common over-identification (Halmoy et al. 2010) have already been without careful assessment (Sibley et al. 2018). However, suggested in the literature. Gender differences were consist- as Matte et al. (2015) pointed out about the DSM-5 adult ently reported in the prevalence of comorbid conditions in ADHD criteria, “The proposed new impulsivity symptoms adults with ADHD. Specifically, SUD (alcohol use), conduct for adults do not improve ADHD diagnosis enough to over- disorder (CD), antisocial PD were more prevalent among come potential negative effects of changing the criteria. males, while MD, dysthymia, and anxiety disorders were However, fewer symptoms than the six-of-nine threshold more prevalent among females with ADHD in the majority required by DSM-IV provided the best cutoff point for iden- of the studies (Biederman et al. 1993; Sobanski et al. 2007; tifying adults who are impaired.” Sprafkin et al. 2007; Wilens et al. 2009). Nonetheless, Bie- The proper diagnosis and treatment of comorbid ADHD derman (2004) reported on no moderating effect of gender and other psychiatric disorders is important, since they may on psychiatric comorbidity with ADHD in adults. lead to higher rates of unfavorable outcomes. Available evi- Other possible moderating factors for the rate of comor- dence suggests that ADHD is associated with earlier onset bidity in/with ADHD could be the severity of ADHD and of comorbid disorders, such as alcoholism and “ADHD in the diagnostic criteria used for ADHD (Bitter et al. 2010). combination with a comorbid disorder (depression, anxiety This has been supported by the findings indicating that disorder, etc.) additionally increases the risk of developing ADHD symptom severity is signic fi antly correlated with the 1 3 88 I. Bitter et al. American Psychiatric Association (2013) Diagnostic and statistical occurrence of lifetime depressive episodes in both males and manual of mental disorders, 5h edn. American Psychiatric Asso- females (Simon et al. 2013). ciation, Arlington Our data underline the need for better training for the Asherson P, Chen W, Craddock B, Taylor E (2007) Adult attention- recognition of adult ADHD comorbid with substance use deficit hyperactivity disorder: recognition and treatment in general adult psychiatry. Br J Psychiatry 190:4–5 and other mental disorders. Asherson P, Young AH, Eich-Höchli D, Moran P, Porsdal V, Deberdt W (2014) Differential diagnosis, comorbidity, and treatment of attention-deficit/hyperactivity disorder in relation to bipolar disorder or borderline personality disorder in adults. Curr Med Limitations Res Opin 8:1657–1672 Balazs J, Kereszteny A (2017) Attention-deficit/hyperactivity dis- The major limitation of this study is its cross-sec- order and suicide: a systematic review. World J Psychiatry tional design, which does not permit to establish causal 7:44–59 Balázs J, Bitter I, Hideg K, Vitrai J (1998) A MINI és a MINI Plusz relationships. kérdõív magyar nyelvû változatának kidolgozása. (Development of the Hungarian version of the MINI and MINI Plus question- Acknowledgements Open access funding provided by Semmelweis naires). Psychiatria Hung 13:160–168 University (SE). The authors would like to thank Drs. Anna Angyalosi Biederman J (2004) Impact of comorbidity in adults with attention- and Zuzana Kratochvílová, Ágnes Bán Gérecz, Berta Hamza Erdélyi, deficit/hyperactivity disorder. J Clin Psychiatry 65(Suppl 3):3–7 Enikő Németh and Dóra Uram for their contribution to the data collec- Biederman J, Faraone SV, Spencer T, Wilens T, Norman D, Lapey KA tion and Ms. Márta Kovács for the logistical support. et al (1993) Patterns of psychiatric comorbidity, cognition, psy- chosocial functioning in adults with attention deficit hyperactivity Funding E. Lilly supported part of this study providing an Investiga- disorder. Am J Psychiatry 150:1792–1798 tors Initiated Grant to Drs. Bitter and Mohr. The Sponsor reviewed the Biederman J, Ball SW, Monuteaux MC, Mick E, Spencer TJ, McCreary proposal and received a copy of the submitted manuscript; however, M et al (2008) New insights into the comorbidity between ADHD they had no role in the planning and implementation of the study, draft- and major depression in adolescent and young adult females. J Am ing and submission of the manuscript or in any other parts of this study. Acad Child Adol Psychiatry 47:426–434 Bitter I, Simon V, Balint S, Meszaros A, Czobor P (2010) How do different diagnostic criteria, age and gender affect the prevalence Compliance with ethical standards of attention deficit hyperactivity disorder in adults? An epide- miological study in a Hungarian community sample. Eur Arch Conflict of interest The authors declare that beyond the above dis- Psychiatry Clin Neurosci 260:287–296 closed funding have no conflict of interest. Buitelaar JK, Kan CC, Asherson P (2011) ADHD in adults. Charac- terization, diagnosis, and treatment. Cambridge University Press, Statement on human rights All procedures performed in studies involv- New York ing human participants were in accordance with the ethical standards of Chang Z, Lichtenstein P, D’Onofrio BM, Sjölander A, Larsson H the institutional and/or national research committee and with the 1964 (2014) Serious transport accidents in adults with attention-deficit/ Helsinki declaration and its later amendments or comparable ethical hyperactivity disorder and the effect of medication: a population- standards. The protocol and the patient information and informed con- based study. JAMA Psychiatry 71:319–325 sent forms of this non-interventional study were approved by the ethics Chen Q, Sjölander A, Runeson B, D’Onofrio BM, Lichtenstein P, committees for the Department of Psychiatry and Psychotherapy, Sem- Larsson H (2014) Drug treatment for attention-deficit/hyperac- melweis University in Budapest, Hungary and for the Prague Psychiatric tivity disorder and suicidal behaviour: register based study. BMJ Center/National Institute of Mental Health, Czech Republic. During the 348:g3769. https ://doi.org/10.1136/bmj.g3769 course of the study, a third study site (second Czech site) was added, Conners CK, Erhardt D, Sparrow EP (1999) Conners’ Adult ADHD Psychiatric Clinic University Hospital in Olomouc, in order to increase Rating Scales (CAARS). Multi-Health Systems Inc, North subjects’ enrollment. The change was approved by the Ethics Committee. 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Journal

ADHD Attention Deficit and Hyperactivity Disorders – Springer Journals

Published: Mar 29, 2019

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