- Email: [email protected]
hyperactivity disorder in referred children and adolescents
Comprehensive Psychiatry 47 (2006) 42 – 47 www.elsevier.com/locate/comppsych
Comorbidity of obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in referred children and adolescents Gabriele MasiT, Stefania Millepiedi, Maria Mucci, Nicoletta Bertini, Chiara Pfanner, Francesca Arcangeli IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, 56018 Calambrone Pisa, Italy
Abstract Objective: The aim of this study was to explore whether comorbid attention-deficit/hyperactivity disorder (ADHD) affects the clinical expression and outcome of obsessive-compulsive disorder (OCD) in a clinical sample. Method: A consecutive series of 94 children and adolescents (mean age, 13.6 F 2.8 years) with current diagnosis of OCD were included in the study. Twenty-four (25.5%) patients were diagnosed as having a comorbid ADHD. Subjects with OCD plus ADHD were compared with subjects with OCD but without ADHD. Results: Comorbid ADHD with OCD was significantly associated with a higher rate of males, an earlier onset of OCD, a greater psychosocial impairment, and a heavier comorbidity, namely, with bipolar disorder, tic disorder, and oppositional defiant disorder/conduct disorder. Phenomenology of obsessions and compulsions and outcome were not affected by ADHD comorbidity. Conclusions: A screening for ADHD should be performed in patients with OCD, as these patients and their parents are frequently not aware that the impairment may be partly due to a comorbid ADHD. D 2005 Elsevier Inc. All rights reserved.
1. Introduction Children and adolescents with obsessive-compulsive disorder (OCD) have been found to have high rates of comorbidity with attention-deficit/hyperactivity disorder (ADHD) [1-3], ranging from 10% to 33% [3,4]. In this kind of comorbidity, as well as in several others, there is still debate as to whether inattention, impulsivity, and, to a lesser degree, hyperactivity are consequences of OCD and related anxiety symptoms or represent a true co-occurring ADHD [5]. Obsessive ideation, impairing compulsions, and the doubts and the real or imagined constraints to the rituals aimed at relieving anxiety can determine symptoms that phenomenologically resemble those of ADHD [6]. When the OCD-ADHD represents a true comorbidity, it may have significant clinical implications from both clinical and neurobiological points of view. From a clinical perspective, given that the most important treatments of ADHD and OCD, that is, stimulants and serotonergic agents (SRIs), respectively, do not overlap, a careful diagnosis of each T Corresponding author. Tel.: +39 50 886111; fax: +39 50 886247. E-mail address: [email protected] (G. Masi). 0010-440X/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.comppsych.2005.04.008
disorder can improve efficacy of our treatment of these patients [7]. Furthermore, the identification of a comorbid ADHD may help to identify a specific subgroup of patients with OCD with more homogeneous course, outcome, and response to treatments. From a neurobiological point of view, the identification of common biologic pathways may help to more clearly define the links in the pathophysiology of both the disorders, which are still under study. For example, patients with OCD have been shown to present a variety of cognitive deficits related to frontal and/or striatal functions, which have been also implicated in ADHD pathophysiology. Schmidtke et al [8] found that patients with OCD, compared with normal controls, have selective deficits in tasks involving controlled attentional processing and self-guided, spontaneous behavior. Purcell et al [9] showed that patients with OCD had specific cognitive deficits on tasks of executive and visual memory function. Given that neither of these studies reported assessing for ADHD, if these cognitive functioning is found in patients with OCD or if it is evidence of an unrecognized comorbid ADHD is not clear. Even if OCD-ADHD comorbidity appears to be an important topic, relatively few studies have addressed this issue [3,5,7,10,11]. The aim of this study is to consider the
G. Masi et al. / Comprehensive Psychiatry 47 (2006) 42 – 47
clinical implications of ADHD-OCD comorbidity, examining in a large sample of consecutively referred patients with OCD the phenotypic characteristic of OCD in children and adolescents with or without ADHD. 2. Method 2.1. Sample A consecutive series of 94 children and adolescents referred to our Pediatric Psychopharmacology Service during a 3-year period (65 males and 29 females; 61 outpatients and 33 inpatients; age range, 8-18 years; mean age, 13.6 F 2.8 years) with a current diagnosis of OCD according to historical information, a clinical interview, the Diagnostic Interview for Children and Adolescents—Revised (DICA-R) [12], the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) symptom checklist [13,14], and symptoms ratings according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) was included in this study. All subjects with pervasive developmental disorders, psychosis, or mental retardation were excluded. All the patients were naturalistically treated with SRIs (clomipramine, fluoxetine, fluvoxamine, sertraline, paroxetine). Adjunctive pharmacologic treatments (eg, antipsychotics, mood stabilizers) were used for nonresponse to treatment, as well as for comorbid conditions. Psychostimulants were not used because these medications are not currently marketed in Italy, and they were still not available in our hospital during the period considered in this study. Our Service is settled in a tertiary level research hospital with a national catchment for children and adolescents with a wide range of neuropsychiatric disorders. The children were referred by other hospitals, community-based child psychiatrists or pediatricians, or family members. Sociodemographic variables were assessed by the parents’ education and occupation according to the Hollingshead’s two-factor index (unpublished data, 1957). All subjects were in the class II to III (middle to upper-middle socioeconomic status level). Socioeconomic status distribution (highest vs middle categories) and family structure (intact vs monoparental families) did not differ among groups (males-females, children-adolescents). Subjects and parents participated voluntarily after they received detailed information on the characteristics of the assessing instruments and treatment options, and parents gave a written informed consent. The study was approved by the Human Subjects Committee of our hospital. 2.2. Measures The DICA-R was administered individually to the children and adolescents participating in the study and to their parents by separate interviewers. The DICA-R is a structured interview according to DSM-IV, organized in such a way as to explore the presence or absence of each of
43
the symptoms in different psychiatric syndromes. Four trained child psychiatrists administered the clinical interview. The comprehension of the questions was carefully assessed; if necessary, they were repeated to clarify the subject’s response. All subjects participating in the study were considered competent to undergo the diagnostic interview. To improve the reliability and validity of the diagnosis, after each interview, clinical data from each subject-parent pair were reviewed by the research clinicians to arrive at consensus. When questions arose, patients and parents were reassessed for further clarification. Structured interview diagnoses (OCD and comorbidities) were considered positive only if DSM-IV criteria were unequivocally met. To assess OCD phenomenology, the Y-BOCS symptom checklist was administered to children and parents. This scale includes more than 60 symptoms organized according to 15 separate categories of obsessions and compulsions. Obsessions and compulsions were grouped in 4 categories according to findings from previous factor analyses of the Y-BOCS symptom checklist in patients with OCD [15,16]. The categories were as follows: aggressive, sexual, religious, and somatic obsessions and checking compulsions; symmetry obsessions and ordering, counting, and repeating compulsions; contamination obsessions and cleanliness and washing compulsions; and hoarding obsessions and compulsions. Although subjects frequently reported obsession and compulsions from more than one category, only the most significant and impairing symptoms were considered, according to Y-BOCS data, to reduce the overlap among the groups. The severity of the illness at baseline and subsequent improvement during follow-up were assessed by means of the Clinical Global Impression (CGI) Severity and Improvement scores [17]. Clinical Global Impression– Severity (CGI-S) score is a single item, recorded at the baseline, that rates the severity of global symptoms on a scale from 1 (bnormalQ) to 7 (bextremely illQ). Clinical Global Impression–Improvement (CGI-I) score is a single item, recorded during the follow-up, that rates behavior from 1 (bvery much improvedQ) to 7 (bvery much worsenedQ). Participants were considered responders to treatment when their CGI-I score was 1 or 2 (very much improved or bmuch improvedQ). Furthermore, functional impairment was assessed with the Children’s Global Assessment Scale (C-GAS) [18], which describes the severity of functional impairment on a scale from 0 (severe impairment) to 100 (superior functioning). 2.3. Statistical analyses Descriptive analyses were used to analyze demographic and clinical characteristics of the whole sample. v 2 Analyses were performed on categorical variables and an unpaired t test or analysis of variance on continuous variables. Considering the large number of comparisons performed and the number of subjects in each group, our
44
G. Masi et al. / Comprehensive Psychiatry 47 (2006) 42 – 47
results are prone to both type I and type II errors. However, given the exploratory nature of our study, P values were based on 2-tailed tests with a = .05, without the Bonferroni correction. 3. Results Obsessive-compulsive disorder resulted frequently comorbid with other mental disorders [6]. Anxiety disorders were more frequently associated with OCD: 44 (46.8%) patients had a generalized anxiety disorder, 25 (26.6%) a separation anxiety disorder, 16 (17.0%) a panic disorder, 34 (36.2%) a social phobia, and 18 (19.1%) simple phobias. Mood disorders were frequently reported as well: 28 (29.8%) patients had a depressive disorder and 23 (24.5%) a bipolar disorder. Disruptive behavior disorders were reported in a strong minority of patients: 24 (25.5%) had ADHD, 13 (13.8%) oppositional defiant disorder, and 11 (11.7%) conduct disorder. Twenty-six (27.7%) patients had a comorbid tic disorder (including Tourette’s syndrome). Table 1 Clinical characteristics of children and adolescents with OCD, with or without ADHD
Sex (male), n (%) Inpatients, n (%) Age, mean (SD) Age at onset of OCD, mean (SD) Age at onset of ADHD, mean (SD) Follow-up (mo) CGI-S CGI-I C-GAS Responders, n (%) Comorbidity, n (%) Generalized anxiety disorder Separation anxiety disorder Panic disorder Social phobia Simple phobia Depression Bipolar disorder Tic Oppositional defiant disorder/conduct disorder Comorbid disorders, mean (SD) Pharmacotherapy, n (%) SRIs alone Mood stabilizers Atypical antipsychotics
OCD (n = 70)
OCD + ADHD (n = 24)
44 23 13.9 10.9
21 10 13.0 9.1
(62.9) (32.9) (2.7) (2.7) –
11 5.3 2.0 44 49
(6) (1) (.7) (9.3) (70.0)
(87.5) (41.7) (3.9) (3.9)
t or v 2
4 3 1.2 2.6
P
.046T .594 .215 .010T
3.8 (1.2) 11 5.3 2.4 39.4 14
(6) (.7) (.6) (5.1) (58.3)
.000 .000 2.5 2.3 6
1.000 1.000 .014T .024T .425
35 (50.0)
9 (37.5)
.7
.411
20 (28.6)
5 (20.8)
.2
.636
13 28 15 24 12 15 13
(18.6) (40.0) (21.4) (34.3) (17.1) (21.4) (18.6)
3 6 3 4 11 11 11
(12.5) (25.0) (12.5) (16.7) (45.8) (45.8) (45.8)
.1 1.1 .4 3.2 6.5 4.1 5.6
.713 .283 .510 .073TT .011T .041T .018T
2.5 (1.2)
3.5 (1.3)
3.4
.000T
38 (54.3) 15 (21.4) 15 (21.4)
9 (37.5) 12 (50.0) 10 (41.7)
1.4 5.8 2.8
.237 .016T .095
T P b .05 (statistically significant). TT P b .08 (trend to significance).
Table 2 Phenomenology of obsession and compulsions in children and adolescents with OCD, with or without ADHD
Ordering Aggressive Contamination Hoarding
OCD (n = 70)
OCD + ADHD (n = 24)
v2
PT
31 25 23 5
14 6 6 2
.9 .5 .2 .07
.341 .477 .643 .796
(44.3) (35.7) (32.9) (7.1)
(58.3) (25) (25) (8.3)
Values are expressed as number (%). T P b .05 (statistically significant).
A comparison between subjects with OCD with and without ADHD comorbidity showed that subjects with cooccurring OCD-ADHD were more frequently males (87.5% vs 62%, v 2 = 4, df = 1, P = .046). The onset of OCD was earlier in subjects with comorbid ADHD (9.1 F 3.9 vs 10.9 F 2.7, t = 2.6, df = 92, P = .010). Furthermore, although severity at the baseline was similar according to the CGI-S, subjects with OCD plus ADHD showed a greater functional impairment, assessed with the C-GAS (39.4 F 5.1 vs 44 F 9.3, t = 2.3, df = 92, P = .024). Finally, clinical improvement assessed after a 6-month follow-up with the CGI-I was lower when ADHD co-occurred (2.4 F .6 vs 2.0 F .7, t = 2.5, df = 92, P = .014), although the rate of responders to treatment (CGI-I 1 or 2) was not significantly different between the 2 groups (Table 1). Comorbidity was slightly different in the 2 groups. Subjects with OCD and ADHD showed higher rates of comorbid disorders (3.5 F 1.3 vs 2.5 F 1.2, t = 3.4, df = 92, P = .000), namely, significantly higher rates of bipolar disorder (45.8% vs 17.1%, v 2 = 6.5, df = 1, P = .011), tic disorder (45.8% vs 21.4%, v 2 = 4.1, df = 1, P = .041), and oppositional defiant disorder/conduct disorder (45.8% vs 18.6%, v 2 = 5.6, df = 1, P = .018) and a trend to a lower rate of depression (16.7% vs 34.3%, v 2 = 3.2, df = 1, P = .073). According to the pharmacologic treatment, subjects with comorbid ADHD received mood stabilizers more frequently than subjects with pure OCD (50% vs 21.4%, v 2 = 5.8, df = 1, P = .016). The rate of patients with OCD responding to a SRIs monotherapy was not affected by comorbid ADHD. Phenomenology of obsession/compulsions was not affected by ADHD comorbidity (Table 2). 4. Discussion The aim of our study was to explore the clinical implications of ADHD comorbidity in a sample of children and adolescents with OCD referred for a pharmacologic treatment with SRIs. This was a consecutive naturalistic sample, in that all the patients with OCD without psychotic disorder, pervasive developmental disorder, or mental retardation who needed a pharmacologic treatment with SRIs were included in this study. In our sample of children and adolescents with OCD, 25.5% resulted to have a comorbid ADHD. This rate is consistent with recent studies addressing this neglected
G. Masi et al. / Comprehensive Psychiatry 47 (2006) 42 – 47
comorbidity [3,5]. This high co-occurrence seems to be bidirectional, high rates of OCD being reported in children with ADHD [10]. As previously reported [5], ADHD preceded the OCD by several years in almost all the cases. The preponderance of males in our study is consistent with most of the studies on referred children and adolescents with juvenile OCD [1,19-21], as well as with ADHD [22]. Consistent with previous reports [5,11], in all the children, the onset of ADHD preceded the onset of OCD. Age at onset of OCD was earlier when an ADHD was comorbid. This phenomenon has been previously reported in bipolar disorder, the onset of which was earlier when an ADHD was co-occurring [23-25]. Similarly, when age at onset of OCD was considered in subjects with or without comorbid bipolar disorder, subjects with comorbid bipolar disorder resulted to have had an earlier onset of OCD [26]. Given the complex interactions of ADHD, OCD, and bipolar disorder in children and adolescents, the timing of the onset of these disorders when they are co-occurring deserves further research. In our sample, functional impairment at the baseline was higher, and improvement after a 6-month follow-up was lower when an ADHD was comorbid. Given that measures of impairment and improvement were global, it is difficult to disentangle the contribution of each comorbid disorder to both impairment and outcome. For example, subjects with comorbid ADHD showed a significantly higher rate of cooccurring disorders, which may have affected the global improvement. Another important issue is that the best treatment of ADHD (ie, psychostimulants) was not used in this study, and this may limit the generalization of this finding. Consistent with other reports, most of our subjects with OCD had other mental disorders, mainly anxiety disorders (generalized anxiety disorder, social phobia, simple phobias, separation anxiety disorder, and panic disorder), confirming that these disorders are most frequently co-occurring during childhood and adolescence [6,26,27]. However, this high co-occurrence was not affected by the ADHD comorbidity. It is noteworthy that even if the relationship between OCD and tic disorder, bipolar disorder, and disruptive behavior disorders has been documented, the comorbidity with ADHD resulted to significantly increase all these 3 connections. This issue may have clinical relevance, given that specific comorbidities can delineate specific subtypes of disorders in terms of phenomenology, natural history, and response to treatments. The reciprocal relationships among ADHD, OCD, and bipolar disorder are particularly intriguing. Epidemiologic and clinical studies reported that ADHD is a frequent antecedent of juvenile bipolar disorder, albeit the nature of this relationship is not well understood [23,25,28]. A number of authors have reported a comorbid ADHD in 20% to 30% of adolescents with bipolar disorder [25,29], and significantly higher rates have been identified in prepubertal children, even when children were assessed after removing overlapping symptoms [23,28]. Fewer
45
systematic data are available on the comorbidity between OCD and bipolar disorder. In a national survey conducted among the French Association of patients with OCD (N = 628), 30% of the subjects presented lifetime comorbid hypomanic episodes and almost 50% were classified as cyclothymic [30]. These findings are consistent with evidence on bipolar children and adolescents [26,31], according to which bipolar risk is higher in very early onset OCD. According to our data, when ADHD is associated, bipolar proneness of OCD is significantly increased. This finding may have clinical relevance because an SRIs treatment in subjects with comorbid OCD-ADHD may more easily result in a pharmacologic hypomania, erroneously interpreted as a nonspecific bbehavioral activation.Q Another intriguing pattern of comorbidity is among ADHD, OCD, and oppositional defiant disorder/conduct disorder. A strong minority of children and adolescents with OCD has these types of externalizing disorders, and in these patients, behavioral dyscontrol may be more impairing than OCD symptoms themselves [3]. Given that ADHD is by itself a risk factor for oppositional defiant disorder/ conduct disorder [32], when the 2 mental disorders are cooccurring, it should be carefully considered the risk of worsening of disruptive behavioral disorders, especially during adolescence. A third important pattern of comorbidity is among ADHD, OCD, tic disorders, and Tourette’s syndrome, given that ADHD comorbidity further increases the risk for tic disorder in patients with OCD. This pattern may stem from the partial overlap of neurobiological basis of the 2 disorders [33,34]. When Tourette’s syndrome is associated with comorbid ADHD and/or OCD, this clinical subtype is more often characterized by a higher frequency of aggressive behavior and explosive outbursts of rage, independent of tic severity or age [35]. Obsessions and compulsions were grouped according to the factorial analytic model of Y-BOCS items of Leckman et al [15,16]. Different subtypes were equally distributed among the subjects, except for hoarding-collecting obsessions and compulsions, which were more rare. Phenomenology of obsessions and compulsion did not result to be affected by comorbidity with ADHD. This finding is consistent with that of Geller et al [11]. Moll et al [10] assessed with the Leyton Obsessional Inventory, Child Version [36], the obsessive-compulsive behaviors in children with ADHD and found that symptoms were not specific, focusing on dirt and contamination, repetition, overconscientiousness, and hoarding (sexual and aggressive contents were not assessed in that study). Our findings are consistent with the recent study of Geller et al [11] using the Child Behavior Checklist [37], a parent-rated, empirically derived, dimensional questionnaire. According to this study, children with OCD plus ADHD, compared with peers with OCD without ADHD, presented higher social and attentional problems, as well as higher scores at the delinquent and aggressive scale. On the
46
G. Masi et al. / Comprehensive Psychiatry 47 (2006) 42 – 47
contrary, children with OCD but without comorbid ADHD had higher scores at the internalizing problem scales (thought problems, somatic complaints) and lower scores at the externalizing problems scales. These results confirm previous findings from the same research group using a diagnostic interview [5] and suggest that the effects of comorbidity are not due to an assessor bias, which is inherent in structured interviews. Our naturalistic study presents several methodological limitations. First of all, only subjects with OCD who needed pharmacologic treatment were included, and this selection bias may limit the generalization of the conclusions because our sample may represent a subgroup of more severely impaired subjects in terms of clinical presentation, pattern of comorbidity, and response to treatments. Furthermore, it is possible that severity of the symptoms and rates of comorbidity are greater in samples referred to our thirdlevel hospital than in subjects followed up in more routine conditions. Another limitation in our study is that we have used CGI as outcome measure, which is not a specific measure of the severity and improvement of OCD and ADHD symptoms. Considering the high level of comorbidity, it may be difficult to disentangle the specific contribution of the cooccurring disorders to the severity of symptoms, as well as the specific effect of pharmacotherapy on OCD symptoms. A third limitation is that the best pharmacologic treatment of ADHD (ie, psychostimulants) was not available during this study. This may have affected the frequency with which other medications were used, as well as the rate of clinical improvement. Our findings are, however, clinically relevant because they describe an unselected sample of children with OCD treated with SRIs in an ordinary clinical setting. No exclusion criteria were applied (except for mental retardation, pervasive developmental disorders, and psychosis), and all comorbid conditions, which are often excluded in controlled trials but represent the rule in clinical settings, were included in the study. Furthermore, all of the patients with OCD were treated as needed (monopharmacy or polypharmacy) and followed up in a routine clinical setting. Long-term, naturalistic, prospective studies might represent an important source of information regarding the effectiveness of a treatment over extended periods under routine clinical conditions. Patients with OCD and their parents are frequently not aware that their impairment may be partly due to a comorbid ADHD, which can occur in about a quarter of the subjects. This notion supports the issue that a screening for ADHD should be performed in all the patients with OCD [38].
References [1] Hanna GL. Demographic and clinical features of obsessive-compulsive disorder in children and adolescents. J Am Acad Child Adolesc Psychiatry 1995;34:28 - 35.
[2] March JS, Leonard HL. Obsessive-compulsive disorder in children and adolescents: a review of past ten years. J Am Acad Child Adolesc Psychiatry 1996;35:1265 - 73. [3] Geller DA, Biederman J, Griffin S, Jones S, Lefkowitz TR. Comorbidity of juvenile obsessive-compulsive disorder with disruptive behavior disorder. J Am Acad Child Adolesc Psychiatry 1996;35: 1637 - 46. [4] Riddle M, Scahill L, King R. Obsessive compulsive disorder in children and adolescents: phenomenology and family history. J Am Acad Child Adolesc Psychiatry 1990;29:766 - 72. [5] Geller DA, Biederman J, Faraone SV, Cradock K, Hagermoser L, Zaman N, et al. Attention-deficit/hyperactivity disorder in children and adolescents with obsessive compulsive disorder: fact or artifact? J Am Acad Child Adolesc Psychiatry 2002;41:52 - 8. [6] Masi G, Millepiedi S, Mucci M, Bertini N, Milantoni L, Arcangeli F. A naturalistic study of referred children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry [in press]. [7] Geller DA, Biederman J, Faraone S, Spencer T, Doyle R, Mullin B, et al. Re-examining comorbidity of obsessive-compulsive and attention deficit hyperactivity disorder using an empirically derived taxonomy. Eur Child Adolesc Psychiatry 2004;13:83 - 91. [8] Schmidtke K, Schorb A, Winkelmann G, Hohagen F. Cognitive frontal lobe dysfunction in obsessive-compulsion disorder. Biol Psychiatry 1998;28:666 - 73. [9] Purcell R, Maruff P, Kyrios M, Pantelis C. Cognitive deficits in obsessive-compulsive disorder on tests of frontal-striatal function. Biol Psychiatry 1998;43:348 - 57. [10] Moll GH, Eysenbach K, Woerner W, Banaschewski T, Schmidt MH, Rothenbeger A. Quantitative and qualitative aspects of obsessivecompulsive behaviour in children with attention deficit hyperactivity disorder. Acta Psychiatr Scand 2000;101:389 - 94. [11] Geller DA, Coffey B, Faraone S, Hagermoser L, Zaman NK, Farrell CL, et al. Does comorbid attention-deficit/hyperactivity disorder impact the clinical expression of pediatric obsessive-compulsive disorder? CNS Spectr 2003;8:259 - 64. [12] Reich W. Diagnostic interview for children and adolescents—Revised DSM-IV version. Toronto7 Multi-Health Systems; 1997. [13] Goodman WK, Price LH, Rasmussen LH, Mazure C, Fleischmann RL, Hill CL, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use and reliability. Arch Gen Psychiatry 1989;46: 1006 - 11. [14] Goodman WK, Price LH, Rasmussen LH, Mazure C, Delgado P, Heninger GR, et al. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry 1989;46:1012 - 6. [15] Leckman JF, Grice DE, Boardman J, Zhan H, Bitale A, Bondi C, et al. Symptoms of obsessive-compulsive disorder. Am J Psychiatry 1997; 154:911 - 7. [16] Leckman JF, Zhang H, Alsobrook JP, Pauls DL. Symptom dimensions in obsessive-compulsive disorder: toward quantitative phenotypes. Am J Med Genet 2001;105:21 - 30. [17] Guy W. ECDEU assessment manual for psychopharmacology. Rockville (Md)7 National Institute of Mental Health; 1976. [18] Shaffer D, Gould M, Brasic J, Ambrosini P, Fisher P, Bird H, et al. Children’s Global Assessment Scale (CGAS). Arch Gen Psychiatry 1983;40:1228 - 31. [19] Flament MF, Rapoport JL, Berg CJ, Sceery W, Kilts C, Mellstrom B, et al. Clomipramine treatment of childhood obsessive-compulsive disorder. Arch Gen Psychiatry 1985;42:977 - 83. [20] Last CG, Strauss CC. Obsessive-compulsive disorder in childhood. J Anxiety Disord 1989;3:295 - 302. [21] Thomsen PH. Obsessive-compulsive symptoms in children and adolescents: a phenomenological analysis of 61 Danish cases. Psychopathology 1991;24:12 - 8. [22] Biederman J, Mick E, Faraone SV, et al. Influence of gender on attention deficit hyperactivity disorder in children referred to a psychiatric clinic. Am J Psychiatry 2002;159:36 - 42.
G. Masi et al. / Comprehensive Psychiatry 47 (2006) 42 – 47 [23] Faraone SV, Biederman J, Wozniak J, Mundy E, Mennin D, O’Donnell D. Is comorbidity with ADHD a marker for juvenileonset mania? J Am Acad Child Adolesc Psychiatry 1997;36:1046 - 55. [24] Sachs GS, Baldassano CF, Truman CJ, Guille C. Comorbidity of attention deficit hyperactivity disorder with early- and late- onset bipolar disorder. Am J Psychiatry 2000;157:466 - 8. [25] Masi G, Toni C, Perugi G, Millepiedi S, Mucci M, Akiskal HS. Externalizing disorders in consecutively referred children and adolescents with bipolar disorder. Compr Psychiatry 2003;44:184 - 9. [26] Masi G, Perugi G, Toni C, Millepiedi S, Mucci M, Akiskal HS. Obsessive-compulsive-bipolar comorbidity: focus on children and adolescents. J Affect Disord 2004;78:175 - 83. [27] Masi G, Millepiedi S, Mucci M, Poli P, Bertini N, Milantoni L. Generalized anxiety disorder in children and adolescents. J Am Acad Child Adolesc Psychiatry 2004;43:752 - 60. [28] Biederman J, Faraone S, Mick E, et al. Attention deficit and hyperactivity disorder and juvenile mania: an overlooked comorbidity? J Am Acad Child Adolesc Psychiatry 1996;35:997 - 1008. [29] Geller B, Luby J. Child and adolescent bipolar disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1997;36: 1168 - 76. [30] Hantouche EG, Angst J, Demonfaucon C, Perugi G, Lancrenon S, Akiskal HS. Cyclothimic OCD: a distinct form? J Affect Disord 2003; 75:1 - 10. [31] Masi G, Toni C, Perugi G, Mucci M, Millepiedi S, Akiskal HS. Anxiety comorbidity in consecutively referred children and adoles-
[32]
[33]
[34]
[35]
[36]
[37] [38]
47
cents with bipolar disorder: a neglected comorbidity. Can J Psychiatry 2001;46:766 - 71. Newcorn JH, Halperin JM. Attention deficit disorders with oppositionality and aggression. In: Brown TE, editor. Attention deficit disorders and comorbidities in children, adolescents and adults. Washington (DC)7 American Psychiatric Press; 2000. p. 171 - 207. Castellanos FX, Giedd JN, Marsh WL, et al. Quantitative brain magnetic resonance imaging in attention deficit hyperactivity disorder. Arch Gen Psychiatry 1996;53:607 - 16. Spencer T, Biederman J, Harding M, et al. Disentangling the overlap between Tourette’s disorder and ADHD. J Child Psychol Psychiatry 1998;39:1037 - 44. Stephens RJ, Sandor P. Aggressive behaviour in children with Tourette syndrome and comorbid attention-deficit hyperactivity disorder and obsessive-compulsive disorder. Can J Psychiatry 1999;44:1036 - 42. Berg CJ, Rapoport JL, Flament M. The Leyton Obsessional Inventory—Child version. J Am Acad Child Adolesc Psychiatry 1986;25:84 - 91. Achenbach TM, Edelbrock C. Manual for the child behavior checklist. Burlington (Va)7 University of Vermont; 1983. Brown TE. Attention deficit disorders with obsessive-compulsive disorder. In: Brown TE, editor. Attention deficit disorders and comorbidities in children, adolescents and adults. Washington (DC)7 American Psychiatric Press; 2000. p. 209 - 30.
Comorbidity of obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in referred children and adolescents Gabriele MasiT, Stefania Millepiedi, Maria Mucci, Nicoletta Bertini, Chiara Pfanner, Francesca Arcangeli IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, 56018 Calambrone Pisa, Italy
Abstract Objective: The aim of this study was to explore whether comorbid attention-deficit/hyperactivity disorder (ADHD) affects the clinical expression and outcome of obsessive-compulsive disorder (OCD) in a clinical sample. Method: A consecutive series of 94 children and adolescents (mean age, 13.6 F 2.8 years) with current diagnosis of OCD were included in the study. Twenty-four (25.5%) patients were diagnosed as having a comorbid ADHD. Subjects with OCD plus ADHD were compared with subjects with OCD but without ADHD. Results: Comorbid ADHD with OCD was significantly associated with a higher rate of males, an earlier onset of OCD, a greater psychosocial impairment, and a heavier comorbidity, namely, with bipolar disorder, tic disorder, and oppositional defiant disorder/conduct disorder. Phenomenology of obsessions and compulsions and outcome were not affected by ADHD comorbidity. Conclusions: A screening for ADHD should be performed in patients with OCD, as these patients and their parents are frequently not aware that the impairment may be partly due to a comorbid ADHD. D 2005 Elsevier Inc. All rights reserved.
1. Introduction Children and adolescents with obsessive-compulsive disorder (OCD) have been found to have high rates of comorbidity with attention-deficit/hyperactivity disorder (ADHD) [1-3], ranging from 10% to 33% [3,4]. In this kind of comorbidity, as well as in several others, there is still debate as to whether inattention, impulsivity, and, to a lesser degree, hyperactivity are consequences of OCD and related anxiety symptoms or represent a true co-occurring ADHD [5]. Obsessive ideation, impairing compulsions, and the doubts and the real or imagined constraints to the rituals aimed at relieving anxiety can determine symptoms that phenomenologically resemble those of ADHD [6]. When the OCD-ADHD represents a true comorbidity, it may have significant clinical implications from both clinical and neurobiological points of view. From a clinical perspective, given that the most important treatments of ADHD and OCD, that is, stimulants and serotonergic agents (SRIs), respectively, do not overlap, a careful diagnosis of each T Corresponding author. Tel.: +39 50 886111; fax: +39 50 886247. E-mail address: [email protected] (G. Masi). 0010-440X/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.comppsych.2005.04.008
disorder can improve efficacy of our treatment of these patients [7]. Furthermore, the identification of a comorbid ADHD may help to identify a specific subgroup of patients with OCD with more homogeneous course, outcome, and response to treatments. From a neurobiological point of view, the identification of common biologic pathways may help to more clearly define the links in the pathophysiology of both the disorders, which are still under study. For example, patients with OCD have been shown to present a variety of cognitive deficits related to frontal and/or striatal functions, which have been also implicated in ADHD pathophysiology. Schmidtke et al [8] found that patients with OCD, compared with normal controls, have selective deficits in tasks involving controlled attentional processing and self-guided, spontaneous behavior. Purcell et al [9] showed that patients with OCD had specific cognitive deficits on tasks of executive and visual memory function. Given that neither of these studies reported assessing for ADHD, if these cognitive functioning is found in patients with OCD or if it is evidence of an unrecognized comorbid ADHD is not clear. Even if OCD-ADHD comorbidity appears to be an important topic, relatively few studies have addressed this issue [3,5,7,10,11]. The aim of this study is to consider the
G. Masi et al. / Comprehensive Psychiatry 47 (2006) 42 – 47
clinical implications of ADHD-OCD comorbidity, examining in a large sample of consecutively referred patients with OCD the phenotypic characteristic of OCD in children and adolescents with or without ADHD. 2. Method 2.1. Sample A consecutive series of 94 children and adolescents referred to our Pediatric Psychopharmacology Service during a 3-year period (65 males and 29 females; 61 outpatients and 33 inpatients; age range, 8-18 years; mean age, 13.6 F 2.8 years) with a current diagnosis of OCD according to historical information, a clinical interview, the Diagnostic Interview for Children and Adolescents—Revised (DICA-R) [12], the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) symptom checklist [13,14], and symptoms ratings according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) was included in this study. All subjects with pervasive developmental disorders, psychosis, or mental retardation were excluded. All the patients were naturalistically treated with SRIs (clomipramine, fluoxetine, fluvoxamine, sertraline, paroxetine). Adjunctive pharmacologic treatments (eg, antipsychotics, mood stabilizers) were used for nonresponse to treatment, as well as for comorbid conditions. Psychostimulants were not used because these medications are not currently marketed in Italy, and they were still not available in our hospital during the period considered in this study. Our Service is settled in a tertiary level research hospital with a national catchment for children and adolescents with a wide range of neuropsychiatric disorders. The children were referred by other hospitals, community-based child psychiatrists or pediatricians, or family members. Sociodemographic variables were assessed by the parents’ education and occupation according to the Hollingshead’s two-factor index (unpublished data, 1957). All subjects were in the class II to III (middle to upper-middle socioeconomic status level). Socioeconomic status distribution (highest vs middle categories) and family structure (intact vs monoparental families) did not differ among groups (males-females, children-adolescents). Subjects and parents participated voluntarily after they received detailed information on the characteristics of the assessing instruments and treatment options, and parents gave a written informed consent. The study was approved by the Human Subjects Committee of our hospital. 2.2. Measures The DICA-R was administered individually to the children and adolescents participating in the study and to their parents by separate interviewers. The DICA-R is a structured interview according to DSM-IV, organized in such a way as to explore the presence or absence of each of
43
the symptoms in different psychiatric syndromes. Four trained child psychiatrists administered the clinical interview. The comprehension of the questions was carefully assessed; if necessary, they were repeated to clarify the subject’s response. All subjects participating in the study were considered competent to undergo the diagnostic interview. To improve the reliability and validity of the diagnosis, after each interview, clinical data from each subject-parent pair were reviewed by the research clinicians to arrive at consensus. When questions arose, patients and parents were reassessed for further clarification. Structured interview diagnoses (OCD and comorbidities) were considered positive only if DSM-IV criteria were unequivocally met. To assess OCD phenomenology, the Y-BOCS symptom checklist was administered to children and parents. This scale includes more than 60 symptoms organized according to 15 separate categories of obsessions and compulsions. Obsessions and compulsions were grouped in 4 categories according to findings from previous factor analyses of the Y-BOCS symptom checklist in patients with OCD [15,16]. The categories were as follows: aggressive, sexual, religious, and somatic obsessions and checking compulsions; symmetry obsessions and ordering, counting, and repeating compulsions; contamination obsessions and cleanliness and washing compulsions; and hoarding obsessions and compulsions. Although subjects frequently reported obsession and compulsions from more than one category, only the most significant and impairing symptoms were considered, according to Y-BOCS data, to reduce the overlap among the groups. The severity of the illness at baseline and subsequent improvement during follow-up were assessed by means of the Clinical Global Impression (CGI) Severity and Improvement scores [17]. Clinical Global Impression– Severity (CGI-S) score is a single item, recorded at the baseline, that rates the severity of global symptoms on a scale from 1 (bnormalQ) to 7 (bextremely illQ). Clinical Global Impression–Improvement (CGI-I) score is a single item, recorded during the follow-up, that rates behavior from 1 (bvery much improvedQ) to 7 (bvery much worsenedQ). Participants were considered responders to treatment when their CGI-I score was 1 or 2 (very much improved or bmuch improvedQ). Furthermore, functional impairment was assessed with the Children’s Global Assessment Scale (C-GAS) [18], which describes the severity of functional impairment on a scale from 0 (severe impairment) to 100 (superior functioning). 2.3. Statistical analyses Descriptive analyses were used to analyze demographic and clinical characteristics of the whole sample. v 2 Analyses were performed on categorical variables and an unpaired t test or analysis of variance on continuous variables. Considering the large number of comparisons performed and the number of subjects in each group, our
44
G. Masi et al. / Comprehensive Psychiatry 47 (2006) 42 – 47
results are prone to both type I and type II errors. However, given the exploratory nature of our study, P values were based on 2-tailed tests with a = .05, without the Bonferroni correction. 3. Results Obsessive-compulsive disorder resulted frequently comorbid with other mental disorders [6]. Anxiety disorders were more frequently associated with OCD: 44 (46.8%) patients had a generalized anxiety disorder, 25 (26.6%) a separation anxiety disorder, 16 (17.0%) a panic disorder, 34 (36.2%) a social phobia, and 18 (19.1%) simple phobias. Mood disorders were frequently reported as well: 28 (29.8%) patients had a depressive disorder and 23 (24.5%) a bipolar disorder. Disruptive behavior disorders were reported in a strong minority of patients: 24 (25.5%) had ADHD, 13 (13.8%) oppositional defiant disorder, and 11 (11.7%) conduct disorder. Twenty-six (27.7%) patients had a comorbid tic disorder (including Tourette’s syndrome). Table 1 Clinical characteristics of children and adolescents with OCD, with or without ADHD
Sex (male), n (%) Inpatients, n (%) Age, mean (SD) Age at onset of OCD, mean (SD) Age at onset of ADHD, mean (SD) Follow-up (mo) CGI-S CGI-I C-GAS Responders, n (%) Comorbidity, n (%) Generalized anxiety disorder Separation anxiety disorder Panic disorder Social phobia Simple phobia Depression Bipolar disorder Tic Oppositional defiant disorder/conduct disorder Comorbid disorders, mean (SD) Pharmacotherapy, n (%) SRIs alone Mood stabilizers Atypical antipsychotics
OCD (n = 70)
OCD + ADHD (n = 24)
44 23 13.9 10.9
21 10 13.0 9.1
(62.9) (32.9) (2.7) (2.7) –
11 5.3 2.0 44 49
(6) (1) (.7) (9.3) (70.0)
(87.5) (41.7) (3.9) (3.9)
t or v 2
4 3 1.2 2.6
P
.046T .594 .215 .010T
3.8 (1.2) 11 5.3 2.4 39.4 14
(6) (.7) (.6) (5.1) (58.3)
.000 .000 2.5 2.3 6
1.000 1.000 .014T .024T .425
35 (50.0)
9 (37.5)
.7
.411
20 (28.6)
5 (20.8)
.2
.636
13 28 15 24 12 15 13
(18.6) (40.0) (21.4) (34.3) (17.1) (21.4) (18.6)
3 6 3 4 11 11 11
(12.5) (25.0) (12.5) (16.7) (45.8) (45.8) (45.8)
.1 1.1 .4 3.2 6.5 4.1 5.6
.713 .283 .510 .073TT .011T .041T .018T
2.5 (1.2)
3.5 (1.3)
3.4
.000T
38 (54.3) 15 (21.4) 15 (21.4)
9 (37.5) 12 (50.0) 10 (41.7)
1.4 5.8 2.8
.237 .016T .095
T P b .05 (statistically significant). TT P b .08 (trend to significance).
Table 2 Phenomenology of obsession and compulsions in children and adolescents with OCD, with or without ADHD
Ordering Aggressive Contamination Hoarding
OCD (n = 70)
OCD + ADHD (n = 24)
v2
PT
31 25 23 5
14 6 6 2
.9 .5 .2 .07
.341 .477 .643 .796
(44.3) (35.7) (32.9) (7.1)
(58.3) (25) (25) (8.3)
Values are expressed as number (%). T P b .05 (statistically significant).
A comparison between subjects with OCD with and without ADHD comorbidity showed that subjects with cooccurring OCD-ADHD were more frequently males (87.5% vs 62%, v 2 = 4, df = 1, P = .046). The onset of OCD was earlier in subjects with comorbid ADHD (9.1 F 3.9 vs 10.9 F 2.7, t = 2.6, df = 92, P = .010). Furthermore, although severity at the baseline was similar according to the CGI-S, subjects with OCD plus ADHD showed a greater functional impairment, assessed with the C-GAS (39.4 F 5.1 vs 44 F 9.3, t = 2.3, df = 92, P = .024). Finally, clinical improvement assessed after a 6-month follow-up with the CGI-I was lower when ADHD co-occurred (2.4 F .6 vs 2.0 F .7, t = 2.5, df = 92, P = .014), although the rate of responders to treatment (CGI-I 1 or 2) was not significantly different between the 2 groups (Table 1). Comorbidity was slightly different in the 2 groups. Subjects with OCD and ADHD showed higher rates of comorbid disorders (3.5 F 1.3 vs 2.5 F 1.2, t = 3.4, df = 92, P = .000), namely, significantly higher rates of bipolar disorder (45.8% vs 17.1%, v 2 = 6.5, df = 1, P = .011), tic disorder (45.8% vs 21.4%, v 2 = 4.1, df = 1, P = .041), and oppositional defiant disorder/conduct disorder (45.8% vs 18.6%, v 2 = 5.6, df = 1, P = .018) and a trend to a lower rate of depression (16.7% vs 34.3%, v 2 = 3.2, df = 1, P = .073). According to the pharmacologic treatment, subjects with comorbid ADHD received mood stabilizers more frequently than subjects with pure OCD (50% vs 21.4%, v 2 = 5.8, df = 1, P = .016). The rate of patients with OCD responding to a SRIs monotherapy was not affected by comorbid ADHD. Phenomenology of obsession/compulsions was not affected by ADHD comorbidity (Table 2). 4. Discussion The aim of our study was to explore the clinical implications of ADHD comorbidity in a sample of children and adolescents with OCD referred for a pharmacologic treatment with SRIs. This was a consecutive naturalistic sample, in that all the patients with OCD without psychotic disorder, pervasive developmental disorder, or mental retardation who needed a pharmacologic treatment with SRIs were included in this study. In our sample of children and adolescents with OCD, 25.5% resulted to have a comorbid ADHD. This rate is consistent with recent studies addressing this neglected
G. Masi et al. / Comprehensive Psychiatry 47 (2006) 42 – 47
comorbidity [3,5]. This high co-occurrence seems to be bidirectional, high rates of OCD being reported in children with ADHD [10]. As previously reported [5], ADHD preceded the OCD by several years in almost all the cases. The preponderance of males in our study is consistent with most of the studies on referred children and adolescents with juvenile OCD [1,19-21], as well as with ADHD [22]. Consistent with previous reports [5,11], in all the children, the onset of ADHD preceded the onset of OCD. Age at onset of OCD was earlier when an ADHD was comorbid. This phenomenon has been previously reported in bipolar disorder, the onset of which was earlier when an ADHD was co-occurring [23-25]. Similarly, when age at onset of OCD was considered in subjects with or without comorbid bipolar disorder, subjects with comorbid bipolar disorder resulted to have had an earlier onset of OCD [26]. Given the complex interactions of ADHD, OCD, and bipolar disorder in children and adolescents, the timing of the onset of these disorders when they are co-occurring deserves further research. In our sample, functional impairment at the baseline was higher, and improvement after a 6-month follow-up was lower when an ADHD was comorbid. Given that measures of impairment and improvement were global, it is difficult to disentangle the contribution of each comorbid disorder to both impairment and outcome. For example, subjects with comorbid ADHD showed a significantly higher rate of cooccurring disorders, which may have affected the global improvement. Another important issue is that the best treatment of ADHD (ie, psychostimulants) was not used in this study, and this may limit the generalization of this finding. Consistent with other reports, most of our subjects with OCD had other mental disorders, mainly anxiety disorders (generalized anxiety disorder, social phobia, simple phobias, separation anxiety disorder, and panic disorder), confirming that these disorders are most frequently co-occurring during childhood and adolescence [6,26,27]. However, this high co-occurrence was not affected by the ADHD comorbidity. It is noteworthy that even if the relationship between OCD and tic disorder, bipolar disorder, and disruptive behavior disorders has been documented, the comorbidity with ADHD resulted to significantly increase all these 3 connections. This issue may have clinical relevance, given that specific comorbidities can delineate specific subtypes of disorders in terms of phenomenology, natural history, and response to treatments. The reciprocal relationships among ADHD, OCD, and bipolar disorder are particularly intriguing. Epidemiologic and clinical studies reported that ADHD is a frequent antecedent of juvenile bipolar disorder, albeit the nature of this relationship is not well understood [23,25,28]. A number of authors have reported a comorbid ADHD in 20% to 30% of adolescents with bipolar disorder [25,29], and significantly higher rates have been identified in prepubertal children, even when children were assessed after removing overlapping symptoms [23,28]. Fewer
45
systematic data are available on the comorbidity between OCD and bipolar disorder. In a national survey conducted among the French Association of patients with OCD (N = 628), 30% of the subjects presented lifetime comorbid hypomanic episodes and almost 50% were classified as cyclothymic [30]. These findings are consistent with evidence on bipolar children and adolescents [26,31], according to which bipolar risk is higher in very early onset OCD. According to our data, when ADHD is associated, bipolar proneness of OCD is significantly increased. This finding may have clinical relevance because an SRIs treatment in subjects with comorbid OCD-ADHD may more easily result in a pharmacologic hypomania, erroneously interpreted as a nonspecific bbehavioral activation.Q Another intriguing pattern of comorbidity is among ADHD, OCD, and oppositional defiant disorder/conduct disorder. A strong minority of children and adolescents with OCD has these types of externalizing disorders, and in these patients, behavioral dyscontrol may be more impairing than OCD symptoms themselves [3]. Given that ADHD is by itself a risk factor for oppositional defiant disorder/ conduct disorder [32], when the 2 mental disorders are cooccurring, it should be carefully considered the risk of worsening of disruptive behavioral disorders, especially during adolescence. A third important pattern of comorbidity is among ADHD, OCD, tic disorders, and Tourette’s syndrome, given that ADHD comorbidity further increases the risk for tic disorder in patients with OCD. This pattern may stem from the partial overlap of neurobiological basis of the 2 disorders [33,34]. When Tourette’s syndrome is associated with comorbid ADHD and/or OCD, this clinical subtype is more often characterized by a higher frequency of aggressive behavior and explosive outbursts of rage, independent of tic severity or age [35]. Obsessions and compulsions were grouped according to the factorial analytic model of Y-BOCS items of Leckman et al [15,16]. Different subtypes were equally distributed among the subjects, except for hoarding-collecting obsessions and compulsions, which were more rare. Phenomenology of obsessions and compulsion did not result to be affected by comorbidity with ADHD. This finding is consistent with that of Geller et al [11]. Moll et al [10] assessed with the Leyton Obsessional Inventory, Child Version [36], the obsessive-compulsive behaviors in children with ADHD and found that symptoms were not specific, focusing on dirt and contamination, repetition, overconscientiousness, and hoarding (sexual and aggressive contents were not assessed in that study). Our findings are consistent with the recent study of Geller et al [11] using the Child Behavior Checklist [37], a parent-rated, empirically derived, dimensional questionnaire. According to this study, children with OCD plus ADHD, compared with peers with OCD without ADHD, presented higher social and attentional problems, as well as higher scores at the delinquent and aggressive scale. On the
46
G. Masi et al. / Comprehensive Psychiatry 47 (2006) 42 – 47
contrary, children with OCD but without comorbid ADHD had higher scores at the internalizing problem scales (thought problems, somatic complaints) and lower scores at the externalizing problems scales. These results confirm previous findings from the same research group using a diagnostic interview [5] and suggest that the effects of comorbidity are not due to an assessor bias, which is inherent in structured interviews. Our naturalistic study presents several methodological limitations. First of all, only subjects with OCD who needed pharmacologic treatment were included, and this selection bias may limit the generalization of the conclusions because our sample may represent a subgroup of more severely impaired subjects in terms of clinical presentation, pattern of comorbidity, and response to treatments. Furthermore, it is possible that severity of the symptoms and rates of comorbidity are greater in samples referred to our thirdlevel hospital than in subjects followed up in more routine conditions. Another limitation in our study is that we have used CGI as outcome measure, which is not a specific measure of the severity and improvement of OCD and ADHD symptoms. Considering the high level of comorbidity, it may be difficult to disentangle the specific contribution of the cooccurring disorders to the severity of symptoms, as well as the specific effect of pharmacotherapy on OCD symptoms. A third limitation is that the best pharmacologic treatment of ADHD (ie, psychostimulants) was not available during this study. This may have affected the frequency with which other medications were used, as well as the rate of clinical improvement. Our findings are, however, clinically relevant because they describe an unselected sample of children with OCD treated with SRIs in an ordinary clinical setting. No exclusion criteria were applied (except for mental retardation, pervasive developmental disorders, and psychosis), and all comorbid conditions, which are often excluded in controlled trials but represent the rule in clinical settings, were included in the study. Furthermore, all of the patients with OCD were treated as needed (monopharmacy or polypharmacy) and followed up in a routine clinical setting. Long-term, naturalistic, prospective studies might represent an important source of information regarding the effectiveness of a treatment over extended periods under routine clinical conditions. Patients with OCD and their parents are frequently not aware that their impairment may be partly due to a comorbid ADHD, which can occur in about a quarter of the subjects. This notion supports the issue that a screening for ADHD should be performed in all the patients with OCD [38].
References [1] Hanna GL. Demographic and clinical features of obsessive-compulsive disorder in children and adolescents. J Am Acad Child Adolesc Psychiatry 1995;34:28 - 35.
[2] March JS, Leonard HL. Obsessive-compulsive disorder in children and adolescents: a review of past ten years. J Am Acad Child Adolesc Psychiatry 1996;35:1265 - 73. [3] Geller DA, Biederman J, Griffin S, Jones S, Lefkowitz TR. Comorbidity of juvenile obsessive-compulsive disorder with disruptive behavior disorder. J Am Acad Child Adolesc Psychiatry 1996;35: 1637 - 46. [4] Riddle M, Scahill L, King R. Obsessive compulsive disorder in children and adolescents: phenomenology and family history. J Am Acad Child Adolesc Psychiatry 1990;29:766 - 72. [5] Geller DA, Biederman J, Faraone SV, Cradock K, Hagermoser L, Zaman N, et al. Attention-deficit/hyperactivity disorder in children and adolescents with obsessive compulsive disorder: fact or artifact? J Am Acad Child Adolesc Psychiatry 2002;41:52 - 8. [6] Masi G, Millepiedi S, Mucci M, Bertini N, Milantoni L, Arcangeli F. A naturalistic study of referred children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry [in press]. [7] Geller DA, Biederman J, Faraone S, Spencer T, Doyle R, Mullin B, et al. Re-examining comorbidity of obsessive-compulsive and attention deficit hyperactivity disorder using an empirically derived taxonomy. Eur Child Adolesc Psychiatry 2004;13:83 - 91. [8] Schmidtke K, Schorb A, Winkelmann G, Hohagen F. Cognitive frontal lobe dysfunction in obsessive-compulsion disorder. Biol Psychiatry 1998;28:666 - 73. [9] Purcell R, Maruff P, Kyrios M, Pantelis C. Cognitive deficits in obsessive-compulsive disorder on tests of frontal-striatal function. Biol Psychiatry 1998;43:348 - 57. [10] Moll GH, Eysenbach K, Woerner W, Banaschewski T, Schmidt MH, Rothenbeger A. Quantitative and qualitative aspects of obsessivecompulsive behaviour in children with attention deficit hyperactivity disorder. Acta Psychiatr Scand 2000;101:389 - 94. [11] Geller DA, Coffey B, Faraone S, Hagermoser L, Zaman NK, Farrell CL, et al. Does comorbid attention-deficit/hyperactivity disorder impact the clinical expression of pediatric obsessive-compulsive disorder? CNS Spectr 2003;8:259 - 64. [12] Reich W. Diagnostic interview for children and adolescents—Revised DSM-IV version. Toronto7 Multi-Health Systems; 1997. [13] Goodman WK, Price LH, Rasmussen LH, Mazure C, Fleischmann RL, Hill CL, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use and reliability. Arch Gen Psychiatry 1989;46: 1006 - 11. [14] Goodman WK, Price LH, Rasmussen LH, Mazure C, Delgado P, Heninger GR, et al. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry 1989;46:1012 - 6. [15] Leckman JF, Grice DE, Boardman J, Zhan H, Bitale A, Bondi C, et al. Symptoms of obsessive-compulsive disorder. Am J Psychiatry 1997; 154:911 - 7. [16] Leckman JF, Zhang H, Alsobrook JP, Pauls DL. Symptom dimensions in obsessive-compulsive disorder: toward quantitative phenotypes. Am J Med Genet 2001;105:21 - 30. [17] Guy W. ECDEU assessment manual for psychopharmacology. Rockville (Md)7 National Institute of Mental Health; 1976. [18] Shaffer D, Gould M, Brasic J, Ambrosini P, Fisher P, Bird H, et al. Children’s Global Assessment Scale (CGAS). Arch Gen Psychiatry 1983;40:1228 - 31. [19] Flament MF, Rapoport JL, Berg CJ, Sceery W, Kilts C, Mellstrom B, et al. Clomipramine treatment of childhood obsessive-compulsive disorder. Arch Gen Psychiatry 1985;42:977 - 83. [20] Last CG, Strauss CC. Obsessive-compulsive disorder in childhood. J Anxiety Disord 1989;3:295 - 302. [21] Thomsen PH. Obsessive-compulsive symptoms in children and adolescents: a phenomenological analysis of 61 Danish cases. Psychopathology 1991;24:12 - 8. [22] Biederman J, Mick E, Faraone SV, et al. Influence of gender on attention deficit hyperactivity disorder in children referred to a psychiatric clinic. Am J Psychiatry 2002;159:36 - 42.
G. Masi et al. / Comprehensive Psychiatry 47 (2006) 42 – 47 [23] Faraone SV, Biederman J, Wozniak J, Mundy E, Mennin D, O’Donnell D. Is comorbidity with ADHD a marker for juvenileonset mania? J Am Acad Child Adolesc Psychiatry 1997;36:1046 - 55. [24] Sachs GS, Baldassano CF, Truman CJ, Guille C. Comorbidity of attention deficit hyperactivity disorder with early- and late- onset bipolar disorder. Am J Psychiatry 2000;157:466 - 8. [25] Masi G, Toni C, Perugi G, Millepiedi S, Mucci M, Akiskal HS. Externalizing disorders in consecutively referred children and adolescents with bipolar disorder. Compr Psychiatry 2003;44:184 - 9. [26] Masi G, Perugi G, Toni C, Millepiedi S, Mucci M, Akiskal HS. Obsessive-compulsive-bipolar comorbidity: focus on children and adolescents. J Affect Disord 2004;78:175 - 83. [27] Masi G, Millepiedi S, Mucci M, Poli P, Bertini N, Milantoni L. Generalized anxiety disorder in children and adolescents. J Am Acad Child Adolesc Psychiatry 2004;43:752 - 60. [28] Biederman J, Faraone S, Mick E, et al. Attention deficit and hyperactivity disorder and juvenile mania: an overlooked comorbidity? J Am Acad Child Adolesc Psychiatry 1996;35:997 - 1008. [29] Geller B, Luby J. Child and adolescent bipolar disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1997;36: 1168 - 76. [30] Hantouche EG, Angst J, Demonfaucon C, Perugi G, Lancrenon S, Akiskal HS. Cyclothimic OCD: a distinct form? J Affect Disord 2003; 75:1 - 10. [31] Masi G, Toni C, Perugi G, Mucci M, Millepiedi S, Akiskal HS. Anxiety comorbidity in consecutively referred children and adoles-
[32]
[33]
[34]
[35]
[36]
[37] [38]
47
cents with bipolar disorder: a neglected comorbidity. Can J Psychiatry 2001;46:766 - 71. Newcorn JH, Halperin JM. Attention deficit disorders with oppositionality and aggression. In: Brown TE, editor. Attention deficit disorders and comorbidities in children, adolescents and adults. Washington (DC)7 American Psychiatric Press; 2000. p. 171 - 207. Castellanos FX, Giedd JN, Marsh WL, et al. Quantitative brain magnetic resonance imaging in attention deficit hyperactivity disorder. Arch Gen Psychiatry 1996;53:607 - 16. Spencer T, Biederman J, Harding M, et al. Disentangling the overlap between Tourette’s disorder and ADHD. J Child Psychol Psychiatry 1998;39:1037 - 44. Stephens RJ, Sandor P. Aggressive behaviour in children with Tourette syndrome and comorbid attention-deficit hyperactivity disorder and obsessive-compulsive disorder. Can J Psychiatry 1999;44:1036 - 42. Berg CJ, Rapoport JL, Flament M. The Leyton Obsessional Inventory—Child version. J Am Acad Child Adolesc Psychiatry 1986;25:84 - 91. Achenbach TM, Edelbrock C. Manual for the child behavior checklist. Burlington (Va)7 University of Vermont; 1983. Brown TE. Attention deficit disorders with obsessive-compulsive disorder. In: Brown TE, editor. Attention deficit disorders and comorbidities in children, adolescents and adults. Washington (DC)7 American Psychiatric Press; 2000. p. 209 - 30.